reza badalzadeh

Ischemia/reperfusion (IR)-induced ventricular arrhythmia, which mainly occurs after the opening of coronary artery occlusion, poses a clinical problem. This study aims to investigate the effectiveness of pretreatment with coenzyme Q10 (CoQ10) in combination with mitochondrial transplantation on IR-induced ventricular arrhythmias in aged rats.

Myocardial IR induction was performed by left anterior descending coronary artery occlusion for 30 min, followed by re-opening for 24 hr. CoQ10 was administered intraperitoneally at a dosage of 10 mg/kg/day for two weeks before inducing IR. At the start of reperfusion, 500 µl of the respiration buffer containing 6×106±5×105 mitochondria/ml of respiration buffer harvested from the pectorals major muscle of young donor rats were injected intramyocardially. To investigate arrhythmias, the heart’s electrical activity during ischemia and the first 30 min of reperfusion were recorded by electrocardiogram. After 24 hr of reperfusion, cardiac histopathological changes, creatine kinase-MB, nitric oxide metabolites (NOx), oxidative stress markers (malondialdehyde, total anti-oxidant, superoxide dismutase, and glutathione peroxidase), and the expression of genes regulating mitochondrial fission/fusion were measured.

Pretreatment with CoQ10 in combination with mitochondrial transplantation reduced ventricular arrhythmias, cardiac histopathological changes, and creatine kinase-MB levels. Simultaneously, this combined therapeutic approach increased myocardial NOx levels, fostering an improved oxidative balance. It also triggered the down-regulation of mitochondrial fission genes, coupled with the up-regulation of mitochondrial fusion genes. 

The combination of CoQ10 and mitochondrial transplantation demonstrated a notable anti-arrhythmic effect by elevating NOx levels, reducing oxidative stress, and improving mitochondrial fission/fusion in aged rats with myocardial IRI.

Lethal ventricular arrhythmias are a significant clinical concern following reperfusion therapies in elderly patients with myocardial infarction. The combination of multi-target therapies to achieve optimal anti-arrhythmogenesis and improve the chances of successful translation for patient benefit has prompted considerable interest. This study examined the anti-arrhythmic effect of nicotinamide mononucleotide (NMN)/ubiquinol combination treatment following myocardial ischemia/reperfusion (IR) injury in aged rats, with an emphasis on the role of oxidative stress and nitric oxide (NO).

Male Wistar rats (n=30, 22-24 months old, 400-450 g) were randomized into five groups with or without IR and/or NMN and ubiquinol, either alone or in combination. NMN (100 mg/kg/48 hours) was administered intraperitoneally for 28 days before IR, and ubiquinol (30 mg/kg) was injected intravenously at early reperfusion. Electrocardiographic signals were recorded during the ischemia and the first 30 minutes of reperfusion. Two hours after reperfusion, myocardial hemodynamic and LDH release were measured, and the left ventricle samples were obtained to evaluate oxidative stress markers and NO levels.

NMN/ubiquinol combination treatment significantly minimized the occurrence and severity of IR-induced arrhythmias, improved myocardial function, and reduced LDH release (P<0.05). It also decreased MDA content, increased superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activities, and enhanced NO formation (P<0.05). This combined treatment showed greater efficacy than the single treatments.

This study revealed the anti-arrhythmic effect of NMN/ubiquinol combination treatment in IR-treated aged rats, which may be associated with reduced oxidative stress and increased NO formation. This combinational approach deserves more investigation due to its potential to confer better anti-arrhythmic effect during aging.

Obesity and its associated disorders, such as hyperlipidemia, have become a ‎global issue ‎following the consumption of unhealthy, high-fat, and high-‎carbohydrate foods, which ‎burdens the economies and the ‎health systems of human societies ‎worldwide‎.‎‏‎‏ ‏This study aimed to evaluate ‎the effect of oral consumption of 6-gingerol and L-arginine ‎supplements on ‎serum lipid profile (triglyceride, cholesterol, high-density lipoprotein, and ‎low-density lipoprotein), obesity factors, insulin, corticosterone and testosterone hormones, ‎and ‎expression of neuropeptide Y (NPY) gene in high-carbohydrate diet (HCD) ‎induced ‎obese rats. Thirty rats in five groups were fed a diet specific to each ‎group for 12 weeks ‎and then treated with the oral administration of L-arginine ‎‎(200 mg/day) and 6-gingerol (100 ‎mg/day) for twelve weeks. The food and water ‎intake and weight change were then measured‎. In addition, plasma glucose, ‎triglyceride, cholesterol, high-density lipoprotein ‎‎(HDL), very-low-density lipoprotein (VLDL)‎, low-density ‎lipoprotein (LDL), and serum ‎hormone levels, including corticosterone, testosterone, and insulin, were measured, and NPY, ‎Y1, and Y5 receptor gene expression were recorded using real-time PCR. Administration of ‎‎6-gingerol and L-arginine decreased food intake, ‎weight ‎gain‎, glucose levels, insulin levels, ‎and homeostasis model assessment-insulin resistance (HOMA-IR) index compared to ‎the ‎HCD control group. In addition, corticosterone and testosterone levels in the ‎study groups ‎showed a significant decrease (P

A major clinical challenge in ischemic heart disease is the prevention of myocardial injury following ischemia/reperfusion (I/R). Application of natural pharmaceuticals seems to be clinically interesting due to their multiplex activities. Protective effects of troxerutin (TXR) in myocardial I/R injury have been ever demonstrated, nevertheless, the purpose of this study is to explore the role of mitochondrial adenosine triphosphate -sensitive potassium (mitoKATP) channels and toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway in cardioprotective effects of TXR against I/R injury in rats. Male Wistarrats (n=72, 250–300 g, 12 weeks old) were randomized into groups with/without I/R and/or TXR and 5-hydroxydecanoate(5-HD), alone or in combination. To induce I/Rmodel, the langendorff-perfused hearts were subjected to left anterior descending coronary artery (LAD) ligation and re-opening. TXR (150mg/kg/day) was administered for 4 weeks before I/R. Moreover, 5-HD (100 μM) was added to the perfusion solution before the ischemia. Finally, myocardial infarct size, LDH release, protein expression levels of TLR4 and NF-κB, and the levels of pro-inflammatory cytokines (TNF-α and IL-1β) were assessed. TXR preconditioning significantly reduced IS and LDH release (P<0.05). Furthermore, it decreased the expression of TLR4 and NF-κB and the levelof pro-inflammatory cytokines (P<0.05 to P<0.01). Inhibition of mitoKATPchannels by 5-HD significantly reversed the cardioprotective effects of TXR. This work shed some light on the knowledge about the mechanisms involved in the anti-inflammatory effect of TXR preconditioning in myocardial I/R injury. This effect may be partly mediated through mitoKATPchannels opening and subsequent suppression of the TLR4/NF-κB pathway.

Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to the cardiac toxicity. The present study aimed to investigate the combination effect of troxerutin (TRX; It is derived from the flavonoid rutin and has pharmacological properties) and high-intensity interval training (HIIT) on DOX-induced cardiotoxicity and expression of mitophagy genes Mfn2 and Parkin in rat cardiac cells.

Male Wistar rats were randomly divided into five groups (n = 10): 1) Control, 2) DOX, 3) HIIT + DOX, 4) TRX + DOX, and 5) HIIT + TRX + DOX. After the last session of HIIT, the trained and time-matched control rats were injected with DOX (20 mg/kg, ip). To confirm the induction of doxorubicin cardiotoxicity, it was shown that DOX injection increased serum level of lactate dehydogenase from 57±3 U/l to 171±6 U/l. The expression of mitophagy genes including Mfn2 and Parkin was measured by Real-Time PCR.

DOX injection decreased the expression of mitophagy genes Mfn2 and Parkin (P<0.01). The combined effect of HIIT exercise and troxerutine consumption led to a significant increase in the expression of mitophagy genes Mfn2 (P<0.05) and Parkin (P<0.01) compared to the DOX group.

The combined application of HIIT exercise and troxerutin can increase the expression of mitophagy genes Mfn2 and Parkin in cardiac cells of DOX-receiving rats and reduce DOX-induced cardiac toxicity.

Doxorubicin (DOX) is an effective chemotherapy treatment for various cancers, but its use has been restricted due to cardiotoxicity effects. Studies about the protective effect of High-Intensity Interval Training (HIIT) against DOX-induced cardiotoxicity and its mechanisms are rare. This study aimed to investigate the protective effect of HIIT against the DOX-induced cardiotoxicity on the level of miR-499 expression which is widely expressed under the physiological conditions in the cardiomyocytes.

Twenty-four male Wistar rats were randomly assigned into four groups (n=6/group) including DOX (20 mg/kg body weight), HIIT (eight weeks, and seven 4-minutes sets of intervals at 80%–90% of VO2max interspersed with 3 minutes periods at 65%–75% of VO2max), HIIT+DOX and Control groups. The mRNA expression level was determined using the RT-PCR method. One-way analysis of variance followed by Tukey's post hoc test was used for statistical analysis of data (α<0.05).

The results showed that DOX-induction significantly increased the MIR-499 expression in the left ventricular tissue of the rats’ heart (P<0.05). Also, the expression level of MIR-499 was increased after exercise, but this difference was not statistically significant. Exercise before the DOX-induction also led to a significant reduction of MIR-499 expression in the HIIT+ DOX group compared with the DOX group (P<0.05).

Therefore, performing HIIT before DOX induction can reduce the changes in MIR-499 expression caused by DOX. Therefore, HIIT could be a proper strategy for protecting the heart against DOX-induced cardiotoxicity by reducing MIR-499 expression.

Diabetes is one of the major risk factors for ischemic heart disease. The aim of this study was to investigate the effect of antioxidant drug troxerutin (TXR) on ischemia-reperfusion-induced myocardial injury in experimental streptozotocin-induced diabetic rats.

Male Wistar rats (250-270 g) were divided into four groups including control, troxerutin, streptozotocin and streptozotocin + troxerutin groups. Diabetes was induced in the rats by intraperitoneal injection of 50 mg / kg streptozotocin and rats were studied for 10 weeks. Rats in the streptozotocin + tezroxerotin group received troxerotin by oral gavage for 4 weeks from the 7th week onwards. The hearts of the rats in all groups were placed in the Langendrov apparatus after separation from the body and subjected to local ischemia for 30 minutes followed by reperfusion for 60 minutes. The amount of lactate dehydrogenase enzyme in coronary artery as well as the parameters of superoxide dismutase and glutathione peroxidase in myocardial tissue during ischemia-reperfusion were measured using special kits.

Body weight and the amount of superoxide dismutase and glutathione peroxidase enzymes were significantly decreased in the diabetic rats (P <0.05). Troxerutin in the streptozotocin + troxerutin group improved the levels of these enzymes to normal levels (P <0.05), whereas lactate dehydrogenase level decreased in this group (P <0.05).

In this study troxerutin reduced the severity of ischemia-reperfusion injury in the diabetic rats.

Cancers represent an important cause of morbidity and mortality, cause more than 12% of deaths in the world. Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to cardiac toxicity. Troxerutin (TRX) is derived from rutin flavonoids and has multiplex pharmacological properties. The present study aimed to investigate the combined effect of troxerutin and high-intensity interval training (HIIT) on DOX-induced cardiac toxicity and the expression of antioxidant genes in rat hearts.

Male Wistar rats were randomly divided into five groups (n = 10): 1) Control, 2) DOX, 3) HIIT + DOX, 4) TRX + DOX, and 5) HIIT + TRX + DOX. After the last session of HIIT, the trained and time-matched control rats were injected with DOX (20 mg/kg, ip). The Creatine kinase (CKMB) and Lactate dehydrogenase (LDH) changes were measured by spectrophotometry and ELISA. Expression of antioxidant genes was measured by Real-Time PCR.

DOX injection increased serum CKMB and LDH in rats in comparison to the control group (p < 0.05) and (P <0.01), respectively. HIIT exercise and troxerutin, alone or in combination, reduced the serum CKMB and LDH levels (p < 0.05) and their combined effect was greater than those of individual treatments (p < 0.01). DOX injection decreased the expression of Nrf2 and Foxo1 antioxidant genes as compared with a control group (P <0.01). HIIT exercise and troxerutin consumption alone increased the expression of the Foxo1 gene as compared with the DOX group (P <0.05) and their combined effect was greater than either alone (P <0.01). HIIT exercise and troxergotTroxerutin consumption alone increased the expression of the Nrf2 gene insignificantly, but their combined effect was significantly increased (P <0.01).

The combined effect of HIIT exercise and troxerutin is a promising strategy to prevent DOX-induced cardiac toxicity and increase the expression of antioxidant genes in rat hearts.

Myocardial infarction is one of the main causes of mortality in the world and endurance exercise is one of the ways to prevent it. The present study aimed to investigate the effect of endurance training on oxidative stress induced by infusion ischemia in the heart of healthy male rats.

32 two-month-old male Wistar rats were used. Rats after one week of adaptation to the new conditions were randomly divided into four treatment groups with eight mice each: 1) health control group, 2) unhealthy control group, 3) health training group, and 4) unhealthy training group. The health training and unhealthy training groups were subjected to endurance training for eight weeks. To induce ischemia, each mouse received isoproterenol (85 mg/kg) intraperitoneally for two consecutive days. At the end of the experimental period, after anesthesia and isolation of rat and washing with ice-cold saline, then homogenization of heart tissue was performed. The activities of superoxide dismutase, glutathione peroxidase, catalase, and myeloperoxidase enzymes were measured using specific kits and supernatants to evaluate the level of antioxidant activity. ELISA method were used and data analyzed with ANOVA test at the significant level of p < 0.05.

Cardiac ischemia significantly reduced the activity of antioxidant enzymes and increased lipid peroxidation compared to the control (p=0.001) and exercise groups (p=0.002). Also, eight weeks of endurance training without ischemia increased the activity of antioxidant enzymes (p=0.002) and decreased myeloperoxidase compared to the ischemia group (p=0.001).

Increasing endurance training by reducing oxidative stress can have significant therapeutic effects against isoproterenol-induced oxidative stress damage and possibly reduce the complications of ischemic heart failure.

Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to the cardiac toxicity. Troxerutin (TRX) is derived from rutin flavonoids and has multiplex pharmacological properties. The aim of the present study was to investigate the combination effect of high-intensity interval training (HIIT) and troxerutin on DOX-induced cardiac toxicity and indices of mitochondrial function in rat hearts.

Male Wistar rats were randomly divided into five groups (n = 10): 1) Control, 2) DOX, 3) HIIT + DOX, 4) TRX + DOX, and 5) HIIT + TRX + DOX. After the last session of HIIT, the trained and time-matched control rats were injected with DOX (20 mg/kg, ip). The Creatine kinase (CKMB) changes was measured by spectrophotometry and ELISA. Mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential were measured by determining the intensity of relevant fluorescent dyes.

DOX injection increased serum CKMB in rats in comparison to control group (P<0.05). HIIT exercise and troxerutin, alone or in combination, reduced the serum CKMB and mitochondrial ROS levels (P<0.05) and their combined effect was greater than those of individual treatments (P<0.01). DOX injection reduced the mitochondrial membrane potential as compared with control group (P<0.01). While the effect of HIIT training or troxerutin alone were not significant on the mitochondrial membrane potential, their combined application significantly increased the mitochondrial membrane potential compared with DOX group (P<0.05).

The combined effect of HIIT exercise and troxerutin is a promising strategy to prevent the DOX-induced cardiac toxicity and improve mitochondrial function in rat heart.

Overexposure to heat conditions can affect the functioning of the cardiovascular system and may promote cardiovascular disorders. Heat shock induced myocardial injury via increasing endoplasmic reticulum response-mediated apoptosis. This study investigated the impact of pretreatment with Rosa canina (RC), a natural antioxidant, on myocardial damage induced by heat stress exposure and underlying mechanisms in cardiomyocytes in rats.

Sixty adult male Wistar rats were allocated into five groups, including Control: received normal saline (NS), Heat Stress (HS), and HS+RC groups. Animals in the HS groups were subjected to heat stress (43 ºC) for 15 minutes once a day for two weeks. Animals in the HS+RC groups received three doses of RC (250, 500, and 1000 mg/mL) one hour before being subjected to heat shock. The endoplasmic reticulum (ER) transmembrane kinases, including PKR-like endoplasmic reticulum kinase (PERK), immunoreactivity of CCAAT/enhancer-binding protein homologous protein (CHOP), and eukaryotic translation initiation factor 2-alpha (eIF2α) as well as caspase 8 were detected by Western blot. The levels of reactive oxygen species (ROS) were assessed. Moreover, histopathological changes and apoptosis were also assayed in the heart tissue by using histopathological and TUNEL assays.

Heat exposure increased the level of ROS and induced oxidative damage in the heart tissue. The results demonstrated that RC administration decreased the overproduction of ROS induced by heat stress in cardiomyocytes. Moreover, heat stress upregulated the expression of p-PERK, p-eIF2α, and CHOP protein while pretreatment with RC decreased expression of ER stress-related markers in cardiomyocytes. Besides, RC diminished heat stress-induced cellular damage and apoptosis associated with inhibition of caspase 8 activation, a pro-apoptotic protein in cardiomyocytes.

These findings indicate that RC exerts a protective effect on heart tissue, at least in part, through inactivation of PERK/eIF2α/CHOP pathway or inhibition of ER stress and oxidative stresstriggered apoptosis in cardiomyocytes induced by heat stress

There is growing awareness that healthy sleep is an integral part of the quality of life.

The aim of this study was to examine the influence of an exercise training protocol and partial sleep restriction (SR) in male Wistar rats. We also assessed the changes in thyroxine (T4) and norepinephrine (NE) hormones.

Rats were randomly housed in four groups including without exercise without SR (Non-Ex-Non-SR), without exercise with SR (Non-Ex-SR), with exercise without SR (Ex-Non-SR), and with exercise with SR (Ex-SR). The rats in the exercise groups ran on a treadmill for four weeks. Also, the columns-in-water model was applied to induce SR for 16 hours per day for a week. Then, the depressive-like behavior was assessed with the forced swimming test (FST) and blood samples were collected to measure the serum levels of T4 and NE hormones.

Body weight gain was significantly (P < 0.05) lower in exercise groups. During the SR period, weight losses of 24.83 and 15.50 g occurred in the Non-Ex-SR and Ex-SR groups, respectively. The lowest climbing and swimming durations were observed in the Non-Ex-SR group. For sleep-restricted rats, the plasma concentration of T4 was significantly (P < 0.05) lower and the NE level was higher although statistically insignificant.

Taken together, our findings indicated that exercise can reduce the negative effects of sleep restriction. For knowing the negative effects of sleep restriction, we need more basic studies in this area.

This study investigated the effect of combination therapy with vildagliptin and ischemic post-conditioning (IPostC) on myocardial infarction and expression of micro ribonucleic acid miR-140 and miR-125b as the regulators of mitochondrial dynamics in myocardial ischemic-reperfusion (IR) injury of rats with type 2 diabetes mellitus.

Chronic diabetes was induced in rats using a high-fat diet protocol and a low dose of streptozotocin over a period of 3 months. In the last month of the diabetic period, vildagliptin was administered orally for 4 weeks once a day, and IR injury was induced by closing the anterior left coronary artery bypass graft for 35 min followed by reopening of it for 60 min. The IPostC protocol was performed at the onset of reperfusion in 6 alternative cycles of 10-second ischemia and reperfusion. At the end of the experiment, the ischemic region of left ventricles was sampled. The size of the risk area and myocardial infarction were studied by planimetry. The levels of miR-140 and miR-125b expression in the left ventricle were evaluated using real-time PCR.

The combination of vildagliptin and IPostC was able to reduce myocardial infarction compared to untreated diabetic group (p < 0.05),  inhibit the elevated expression of miR-140 caused by IR damage, and increase the expression of miR-125b in diabetic hearts (p < 0.05).

The combination of vildagliptin and IPostC has cardioprotective effect against IR injury in rats with type II diabetes by change in the expression of micro-RNAs involved in cardioprotection.

Adriamycin (ADR) is a useful drug for the treatment of hematologic malignancies and solid tumors. However, its clinical uses are limited due to dose-dependent cardiac toxicity. Contrary to moderate endurance training, there is little research about the protective role of high-intensity aerobic interval training (HIIT) against the ADR-induced cardiac toxicity and its mechanisms. The present study aimed to investigate the protective effect of HIIT against ADR-induced cardiac toxicity in the left ventricle of rats by assessment of the serum biomarkers of cardiac injury (LDH and CK-MB). Twenty-four male Wistar rats were randomly assigned into four groups (n = 6/group): (1) Control; (2) ADR (20 mg/kg.bw); 3) HIIT (7 sets of 4 minutes intervals at 80% - 90% VO2max interspersed with 3 minutes periods of 65% - 75% VO2max, for 8 weeks), and (4) HIIT + ADR. The ELISA method was used for measuring the serum levels of biomarkers. Statistical differences were analyzed using one-way analysis of variance followed by Tukey’s post hoc test for multiple comparisons (α < 0.05). Based on the results, ADR-induction resulted in a significant increase in the LDH and CK-MB levels compared to the ADR group (P < 0.05). Also, the HIIT per se insignificantly increased the levels of LDH and CK-MB compared to the control group. However, the HIIT before ADR-induction resulted in a significant decrease in the LDH and CK-MB levels compared to the ADR group (P < 0.05). Therefore, the HIIT can be a proper non-prescriptive strategy for preventing ADR-induced cardiotoxicity via reducing the serum biomarkers of cardiac injury.

Ischemic heart disease is the principal cause of mortality worldwide. Using natural strategies to prevent this disease is very important. Therefore, the current study aimed to evaluate the combined effects of the cinnamon extract and aerobic exercise on oxidative stress following myocardial ischemia/reperfusion (I/R) injury. Male Wistar rats weighing 250-300 g were randomly divided into 4 groups (6 rats each) including control, cinnamon extract, aerobic exercise, and a combination of cinnamon and exercise. The aerobic exercise was performed on a treadmill and the cinnamon extract was administered by gavage for a month. In addition, the isolated hearts of the rats received global ischemia (30 minutes) and reperfusion (60 minutes) in order to induce I/R injury. Lactate dehydrogenase (the indicator of tissue damage), the marker of lipid peroxidation (malondialdehyde), and antioxidative enzymes (i.e., superoxide-dismutase and glutathione-peroxidase) were measured with specific kits and spectrophotometric methods on samples obtained from the ischemic tissues. Based on the results, lactate dehydrogenase level significantly decreased in the group receiving a combination of cinnamon and aerobic exercise compared to the control group (P < 0.05). Further, both aerobic exercise and cinnamon extract significantly increased the values of antioxidant enzymes and this effect was greater in combination therapy compared to the individual treatments. However, the amount of malondialdehyde in the exercise group and in the combined treatment significantly reduced compared to that of the control groups (P < 0.05). A combination of aerobic training with cinnamon supplementation had better cardioprotective influences. Accordingly, cinnamon may increase the aerobic exercise potency in enhancing the heart antioxidant capacity against oxidative insult in reperfusion injury.

Clinical use of Doxorubicin (DOX), a widely useful drug for the treatment of various cancers, is limited by the cardiotoxicity. Despite the growing attention to the protective role of exercise activity, especially moderate endurance exercises against the DOX-induced cardiotoxicity, few studies have focused on aerobic high-interval interval training (AIT) and its mechanisms. Therefore, the purpose of this study was to investigate the protective effect of AIT against the DOX-induced changes in the PGC-1α mRNA levels in the cardiomyocytes of rats. 24 male Wistar rats were randomly assigned into four groups (n=6/groups): 1) Control; 2) DOX (20 mg/kg body weight)/; 3) AIT (7 sets of 4 min intervals at 80%–90% VO2max interspersed with 3 min periods of 65%–75% VO2max, for 8 weeks before DOX-injection); and 4) AIT + DOX. The mRNA levels also were determined using RT-PCR. For statistical analysis of data, One-way analysis of variance and Tukey's post hoc test were used (α<0.05). DOX-treatment significantly decreased the expression of PGC-1α in the DOX group compared to the Control group (P < 0.05). Also, the expression of PGC-1α significantly increased in the AIT group compared to the Control group (P < 0.05). AIT before DOX-induction also significantly increased the expression of PGC-1α in the AIT+DOX group compared to the DOX group (P < 0.05). AIT could inhibit the DOX-induced changes in the PGC-1α mRNA levels in the cardiomyocytes of rats. AIT could be a good non-prescriptive strategy for preventing of DOX-induced cardiotoxicity.

Diabetic hearts are resistant to cardioprotection by ischemic-postconditioning (IPostC). Protection of diabetic hearts and finding related interfering mechanisms would have clinical benefits. This study investigated the combination effects of vildagliptin (Vilda) and IPostC on cardioprotection and the levels of autophagy and mitochondrial function following myocardial ischemia/reperfusion (I/R) injury in type-II diabetic rats.
Diabetes was established by high fat diet/low dose of streptozotocin and lasted for 12 weeks. The diabetic rats received Vilda (6 mg/kg/day, orally) for one month before I/R. Myocardial regional ischemia was induced through the ligation of left coronary artery, and IPostC was applied immediately at the onset of reperfusion. The infarct size was assessed by a computerised planimetry and left ventricles samples were harvested for cardiac mitochondrial function studies (ROS production, membrane potential and staining) and western blotting was used for determination of autophagy markers.
None of Vilda or IPostC but combination of them could significantly reduce the infarct size of diabetic hearts, comparing to control (P

Chronic diabetes impedes cardioprotection in reperfusion injury and hence protecting the diabetic heart would have important outcomes. In this study, we evaluated whether combined postconditioning with ischemia and cyclosporine-A can restore oxidative stress and histopathological changes in reperfusion injury of the diabetic myocardium.
Streptozocin-induced diabetic rats’ hearts and nondiabetic controls in eight subgroups (with or without receiving ischemic-postconditioning (IPostC), cyclosporine-A, an inhibitor of mitochondrial permeability transition, or both of them) suffered from 30 min regional ischemia followed by 45 min reperfusion on an isolated-heart Langendorff system. The levels of lactate dehydrogenase (LDH) in the coronary effluent, and the levels of oxidative stress markers including 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant capacity (TAC) in myocardial supernatant prepared from the ischemic zone were measured using specific kits, spectrophotometrically. Histopathological studies were performed through the hematoxylin-eosin staining method.
Administration of IPostC and cyclosporine-A (alone or together) in nondiabetic hearts potentially reduced the severity of histological changes and level of LDH release as compared with untreated-controls (P0.1). However, the combined postconditioning with ischemia and CsA exerted significant protective effects in diabetic hearts (P By augmenting the protective effects of IPostC and CsA through their combined application, reperfusion injury and related oxidative stress are reduced in diabetic hearts similar to non-diabetics.

Type 1 diabetes is a chronic disease characterized by the body's inability to produce insulin due to destruction of the beta cells. There is increasing evidence that reactive oxygen species (ROS) play a major role in the development of diabetic complications. The purpose of this study is to investigate the effects of troxerutin administration on oxidative stress markers in blood of STZ-induced diabetic rats. Male Wistar rats were divided into 4 groups as: control (con), control-troxerutin (CON-TRX), diabetes (Dia), diabetic-troxerutin (DIA-TRX). Type 1 diabetes was induced by injection of streptozotocin (STZ) (i.p, 55mg/kg) and lasted for 10 weeks. Animals were received oral administration of troxerutin (150 mg/kg) for 4 weeks. At the end of study, malondialdehyde (MDA, the main product of lipid peroxidation), activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were measured spectrophotometrically. Induction of diabetes with STZ resulted in increased MDA levels and decreased blood antioxidant capacity as compared with those of controls (P<0.05). Pre-treatment of diabetic rats with troxerutin significantly decreased the levels of MDA (P<0.01) and increased the activity of antioxidant enzymes SOD, GPX and CAT compared to untreated-diabetic groups. Troxerutin had no significant influence on non-diabetic rats. These findings showed that troxerutin may prevent oxidative complications of diabetic circumstances by elevating antioxidant enzymes activities and reducing lipid peroxidation.

This study designed to use remote ischemic post conditioning (RIPC) as a protective strategy during percutaneous coronary intervention (PCI) in patients with ST segment elevation myocardial infarction (STEMI) to reduce myocardial cells damage due to reperfusion injury.
Sixty-one patients were divided into test group (32 patients) receiving RIPC and control group (29 patients). Patients were included with first MI who had 20-80 years old. The RIPC protocol was applied on patients arm in three successive episodes during the opening of infarct-related artery (IRA). Whole blood sample were taken from patients after the first episode before IRA opening and after the third episode after IRA opening. The serums were extracted and stored in the freezer -70˚C to determine the levels of glutathione peroxidase (GPX), superoxide dismutase (SOD), total antioxidant capacity (TAC) and malondialdehyde (MDA).
The levels of GPX and SOD after the first episode of RIPC were significantly higher in test group than control group (P The results indicated that RIPC protocol has protective properties in patients with STEMI through enhancing the antioxidant potentials and decreasing lipid peroxidation.

Reperfusion injury is a well-known phenomenon following restoration of the coronary circulation after coronary artery bypass grafting (CABG) that impairs myocardial function. In order to control the severity of this injury, we aimed to investigate the effect of a new conditioning strategy namely ischemic postconditioning (IPOC) along with controlled aortic root reperfusion (CARR) on myocardial protection in CABG surgery with cardiopulmonary bypass.
In a doubled blind clinical trial study, 51 patients undergoing first-time elective CABG were randomly divided in three groups: CARR, IPOC, and combination of IPOC and CARR. At the end of procedure and just before aortic cross-clamp removal, reperfusion was started as following: In CARR-receiving groups, the reperfusion was started with low perfusion pressures for 10 minutes, and in IPOC-receiving groups, three cycles of 1 minute episodes of ischemia separated by 1 minute episodes of reperfusion was applied as postconditioning protocol. Left ventricular ejection fraction (EF) (by echocardiography), inotrope requirement index, and myocardial arrhythmias were measured up to 72 hours after operation.
Echocardiography revealed that the recovery of EF after operation in IPOC group was significantly higher than those of two other groups (P The study suggests that IPOC may provide clinical benefits against reperfusion injury in patients undergoing CABG surgery and maintain the post ischemic left ventricular performance.

Diabetes mellitus as a main risk-factor of ischemic heart disease may interfere with postconditioning’scardioprotective effects. This study aimed to investigate the involvement of glycogen synthase kinase-3β (GSK-3β) and oxidation status in chronic diabetes-induced loss of cardioprotective effect of ischemic-postconditioning (IPostC) in Wistar rats. After 8 weeks of induction of diabetes by streptozotocin (50mg/kg), hearts of control and diabetic rats were isolated and mounted on a constant-pressure Langendorff system. All hearts were subjected to 30min regional ischemia followed by 60min reperfusion (by occluding and re-opening of left anterior descending coronary artery, respectively). IPostC was applied immediately at the onset of reperfusion. At the end of reperfusion, the infarct size of myocardium was measured via computerized planimetry. Myocardial contents of malondealdehyde and glutathione as indices of oxidative status were assayed spectrophotometrically and the total and phosphorylated forms of myocardial GSK- 3β were quantified through western blotting. IPostC reduced the infarct size of control hearts from 41±2.9% to 28±1.9% (P<0.05), whereas it could not induce significant changes in infarct size of diabetic animals (35±1.8% vs. 39±3.1%). IPostC-induced reduction in malondealdehyde and elevation in glutathione contents were significant only in control not in diabetic hearts. The total forms of GSK-3β were similar in all groups; however, the phosphorylation of GSK-3β (at Ser9) by IPostC was greater in control hearts than diabetics (P<0.01). The failure of cardioprotection by IPostC in diabetic hearts may be attributed to the loss of phosphorylation of GSK-3β and thereby increase in oxidative stress in diabetic states.

Serum amyloid-A (SAA) and protein carbonyl group are rigorously related with cardiovascular diseases (CVDs) as a sensitive marker of an acute inflammatory state and as an important index of oxidative stress, respectively. Moreover, diet is one of the main factors that canmodify cardiovascular risks. Therefore, this study aimed to investigate the effects of Ramadanfasting on SAA and protein carbonyl group levels in patients with CVDs. Twenty-one patients (21 male; mean age 52±9 years old) with CVDs (coronaryartery disease, cerebrovascular, or peripheral arterial diseases) were participated in this study.Biochemical parameters were measured in patients 2 days before and 2 days after Ramadanfasting. SAA levels were assessed using enzyme-linked immunosorbent assay and Cayman’sprotein carbonyl colorimetric assay was provided for measuring protein carbonyl groups. According to the findings of the study, post-Ramadan levels of inflammatory biomarker,SAA was decreased significantly in patients with CVDs in comparison with the baseline beforefastingvalues (16.84±8.20 vs. 24.40±6.72 μg/ml, P = 0.021). In addition, Ramadan fastingsignificantly reduced the levels of protein carbonyl group in patients as compared with those ofbaseline values (33.08±15.31 vs. 43.65±16.88 nmol/ml, P = 0.039). Ramadan fasting has impressive effects on modulating CVDs by decreasinginflammation and oxidative stress markers. However, to get a clear conclusion with more results,further investigation is warranted.

The use of herbal medicine instead of antibiotics for treatment of livestock and poultry disease could have many beneficial implication due to their multiplex activities. This study has investigated the effects of cinnamon extract on cyclooxygenase-2 (COX-2) gene expression level in liver and lipid profile alterations in serum of healthy and Escherichia coli infested broiler chickens. Ninety Ross-308 broilers in healthy or E.coli-infected groups were received normal diet or diet supplemented with cinnamon extract in concentrations of 100 or 200 mg/kg of diet. E. coli suspension (108cfu/ml) was injected subcutaneously after 12 days of cinnamon administration. Seventy-two hours after E. coli injection, blood samples were taken for analysis of lipid profile alterations in serum, and then liver tissue samples were obtained for detection of COX-2 gene expression using real-time PCR. Infection with E. coli significantly decreased the levels of COX-2 gene expression as well as some variables of lipid profile including triglyceride level as compared with the control group (p<0.05). Pre-administration of cinnamon extract in broilers diet (in both concentrations) significantly reduced the tissue levels of COX-2 gene expression and triglyceride levels in serum of broiler chickens infected with E. coli in comparison with E. coli-alone group (p<0.05). The cinnamon extract could not induce statistically significant effects on the tested parameters in healthy broilers. Thus, pre-administration of cinnamon extract in diets of broiler chickens may be capable of reducing the inflammatory and oxidative injuries induced by pathologic conditions such as infection with E. coli.

Diabetes is associated with micro- and macro-vascular complications affecting several organs. Oxidative stress plays a crucial role in the etiology of vascular disease in diabetes.. The present study aimed to investigate the beneficial effect of troxerutin on diabetes-induced histopathological damages in rat aorta with focusing on its antioxidative actions.. Male Wistar rats were randomly divided into four groups (n = 8/each): control, control plus troxerutin, diabetic and diabetic plus troxerutin. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg) and lasted for 10 weeks. Troxerutin was administered orally in concentration of 150 mg/kg/daily for one month before killing rats. At the end of treatment period, thoracic aorta was isolated and divided into two parts; one part was immersed in 10% formalin for histopathological evaluations and the other was frozen by liquid nitrogen for assessment of malondialdehyde (MDA, the main product of lipid peroxidation), activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX).. Lipid deposition in tunica intimae and media, thickening and structural deformity of vascular tissues as well as the level of plasma glucose and aortic tissue levels of lipid peroxidation were significantly increased in diabetic rats compared to control ones (P < 0.05). Troxerutin significantly reduced the severity of all vascular histopathological damages in treated versus untreated diabetic rats. In addition, treatment of diabetic rats with troxerutin significantly decreased the levels of MDA (5.1 ± 0.3 vs. 9.3 ± 1.2 nmol/mL) (P < 0.01) and increased the activity of antioxidant enzyme GPX compared to untreated-diabetic groups.. Troxerutin may reduce the vascular complications and tissue injuries induced by chronic diabetes in rat aorta through increasing the activity of tissue antioxidant system and reducing the level of lipid peroxidation..