جستجوی مقالات مرتبط با کلیدواژه « Atorvastatin » در نشریات گروه « پزشکی »

Pomegranate peel extract (PPE) exhibits biological activities with potential therapeutic applications. In this research, the antioxidant properties of the combination of atorvastatin and PPE, and the effect of this combination on the regulation of inflammatory factors and the gene pathway of glucose transport regulation (GLUT4) in tissue fibroblast cells (3T3-L1).

This research was done in a descriptive-analytical way. The percentage of cell survival after treatment with suitable concentrations of aqueous extract of pomegranate peel (AEPP) and atorvastatin drug was obtained. The amount of inflammatory cytokines IL-1, IL-6, and TNF-α in the supernatant solution of treated cells was measured using the ELISA method. Then the antioxidant activity and GLUT4 expression were measured using real-time PCR.

The highest antioxidant capacity is related to the combination of AEPP with atorvastatin. Also, the level of IL-1, TGF-B, and IL-6 cytokines increased. Furthermore, atorvastatin significantly increased the level of GLUT4 in adipocytes compared to the combination of atorvastatin and AEPP concentration, as well as AEPP alone.

The results showed that the combined use of AEPP and Atorvastatin can improve the efficiency of antioxidant pathways in the cell and significantly reduce the level of reactive oxygen. In addition, atorvastatin has a greater effect on regulating the function of inflammatory factors and the adipose glucose transporter 4 (GLUT4) regulatory gene pathway than the combination of atorvastatin and AEPP concentrations. However, more studies are needed in this area.

It has been shown that about 80% of deaths in diabetic patients are caused by cardiovascular disorders, which is called diabetic heart disease. The purpose of this research was to investigate the effect of two types of exercise (continuous and periodic) and the drug atorvastatin on the expression of VEGF and MMP2 genes in the aorta tissue of diabetic rats. In this study, 40 male rats, which were randomly divided into 8 groups: 1) control, 2) diabetic, 3) diabetic+continuous, 4) diabetic+intermittent, 5) atorvastatin, 6) continuous + atorvastatin, 7) intermittent + atorvastatin and 8) saline. Rats performed two types of continuous and periodic training 5 days a week for 8 weeks. Atorvastatin was injected intraperitoneally at a daily dose of 20 mg per kilogram of body weight. To determine the significance of the difference between groups, one-way analysis of variance and Tukey's post hoc test were used. MMP2 levels in the diabetes group significantly increased at the significance level of 0.05 compared to the control group and in the supplement, intermittent, intermittent-supplement and continuous-supplement groups significantly decreased compared to the diabetes group. The levels of VEGF in the diabetes group increased significantly compared to the control and the intermittent-supplement group significantly decreased compared to the diabetes group. There is a possibility that intermittent exercise in combination with atorvastatin can have a protective effect on the aorta through the reduction of VEGF and MMP2 genes in the aortic tissue and the improvement of angiogenesis that was impaired due to the induction of diabetes.

Vascular endothelial growth factor beta (VEGF-β) plays a role in lipid metabolism, contrary to its weak role in angiogenesis. The aim of this study was to determine the effect of training and atorvastatin on the expression of the VEGF-β gene in the liver tissue of diabetic rats.

In this study, 25 rats were divided into control, diabetes, diabetes + exercise, diabetes + atorvastatin, and diabetes + atorvastatin + exercise groups. The interventions included eight weeks of aerobic exercise, running on a treadmill and taking 10 mg of atorvastatin by gavage. After the interventions, the rats were sacrificed and the liver tissue was analyzed. Statistical analysis was performed using one-way analysis of variance and LSD post hoc test.

The results showed that the induction of diabetes led to a significant decrease in hepatic VEGF-β gene expression and an increase in serum glucose and total cholesterol compared to the healthy control group. In the groups of diabetes + exercise and diabetes + atorvastatin + exercise, the increase of VEGF-β and the decrease of glucose and cholesterol were significant compared to the control diabetes and diabetes + atorvastatin groups.

According to the results, it can be said that continuous aerobic training can prevent liver complications caused by diabetes by increasing the expression of VEGF-β gene, however, despite the positive effects of atorvastatin on serum glucose and total cholesterol, it does not have a significant effect on hepatic VEGF-β gene expression in diabetic rats.

Background &

Diabetes is a chronic non-communicable disease characterized by chronic hyperglycemia caused by a defect in the secretion and function of the pancreatic insulin hormone. This disease is a group of metabolic diseases and is considered as a progressive global health problem (1, 2). In general, diabetes is divided into type 1 diabetes, type 2 diabetes and gestational diabetes based on the cause and clinical features (3-5). Type 1 diabetes was recently termed juvenile-onset diabetes or insulin-dependent diabetes mellitus, a condition caused by destruction of pancreatic β-cells by T cells resulting in complete insulin deficiency (2 , 5). Type 1 diabetes represents 5 to 10% of patients with diabetes (2). Type 1 diabetes is characterized by the destruction of more than 90% of β cells. Streptozocin (STZ) is a standard method for inducing diabetes in animals (6). Vascular endothelial growth factor beta (VEGF-β) is one of the obscure members of the VEGF family. It has been reported that the ability of VEGF-β to induce angiogenesis is weak in most tissues. However, VEGF-β appears to be a more tissue-specific vascular growth factor that can have nutritional and metabolic effects (8). In early 2008, Karpanen et al stated that VEGF-β has a weak role in the vascular system; But it has a significant advantage in regulating lipid metabolism (9). Considering the potential of VEGF-β in regulating lipid metabolism, it is expected that this growth factor will become a new target for improving metabolic diseases, such as obesity and diabetes (10). Defects in multiple VEGF-β pathways have been reported to be associated with increased cell apoptosis in diabetes models (11). However, the potential beneficial effects of VEGF-β through increasing blood flow (increasing insulin availability and glucose uptake in target organs) and decreasing FAs uptake (preventing lipotoxicity and improving insulin signaling) and its safety for clinical use , has not yet been determined (21). which indicates the need for more research in this regard. Previous research indicates the positive effects of exercise on blood sugar control and also reducing the complications caused by diabetes (5, 13, 14). Also, one of the main and most effective drugs that have beneficial effects on lipid profile are statins; Among statins, atorvastatin is considered one of the least complicated and most effective. This drug is a selective competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme-A reductase, but unlike other statins, it is a completely synthetic compound that is used in diabetic patients with hypercholesterolemia in combination with other sugar control drugs. The beneficial effect of atorvastatin on some adipokines has been proven and it seems to be one of the mechanisms of the effect of this drug in blood sugar control (15). According to the mentioned information, the present research was conducted with the aim of comparing the effect of eight weeks of interval training and atorvastatin consumption on hepatic VEGF-β gene expression in male Wistar rats’ model of type 1 diabetes.

In this study, 25 mice were divided into Healthy control, diabetes control, diabetes + interval training, diabetes +atorvastatin, and diabetes + atorvastatin+ interval training groups.The interventions included eight weeks of interval training, running on a treadmill and taking 10 mg of atorvastatinby gavage.After the interventions, the mice were sacrificed and the liver tissue was analyzed.Statistical analysis was performed using one-way analysis of variance and Tokey post hoc test.

The results showed that the induction of diabetes caused a significant decrease in hepatic VEGF-β compared to the healthy control group. In the groups of diabetes + interval training, diabetes + atorvastatin and diabetes + atorvastatin + interval training, the increase of VEGF-β was significant compared to diabetes control group (P < 0.001), but no difference was observed between the three intervention groups (P < 0.05).

The results of our research showed that after induction of diabetes, the expression of hepatic VEGF-β gene in diabetic groups was significantly lower than in the healthy control group. The results of Shahavand et al also showed that the induction of diabetes decreased the expression of VEGF-β gene in the heart tissue of diabetic rats (18), which was consistent with the results of the present study. VEGF-β has been reported to be involved in lipid and glucose metabolism (10). Also, in mice in which VEGF-β was knocked out and fed with high fat, in addition to obesity and dyslipidemia, their liver suffered from steatosis and increased insulin resistance (19). Research has shown that VEGF-β can reduce lipid accumulation and restore insulin sensitivity in NAFLD (10); Therefore, the decrease of VEGF-β caused by diabetes is related to the liver complications of diabetes such as hepatic steatosis and hepatic insulin resistance. It can be said that by inducing diabetes and increasing hyperglycemia caused by diabetes, the level of VEGF-β decreases; which can be related to liver complications caused by diabetes such as non-alcoholic fatty liver and apoptosis of hepatocytes. However, Ye et al.'s study reported that plasma VEGF-β levels were significantly higher in subjects with NAFLD compared to subjects without NAFLD, and analysis of covariance confirmed this result (20). The reason for the difference in the results may be due to the difference in the research samples, the difference in the studied tissue, research units or the type of disease. Because in our research, the research samples included diabetic rats treated with streptozotocin, which were different from the research samples of Ye et al. In examining the effect of aerobic exercise on hepatic VEGF-β gene expression, the results of the present study showed that intermittent exercise increased VEGF-β gene expression compared to the control diabetes group. Shahavand et al also reported that six weeks of continuous aerobic exercise increased cardiac VEGF-β gene expression in diabetic rats (18), which is consistent with the results of the present study. Kivelä et al also reported in their research that an exercise training increased the expression of VEGF-β in healthy mice (21). VEGF-β and mitochondrial gene expression are regulated in concert, and endogenous VEGF-β levels are highest in tissues with high metabolic activity, such as heart, skeletal muscle, and brown fat (25). It has been reported that the lack of VEGF-β leads to a decrease in the expression of fatty acid (FA) transfer proteins (Fatp3 and Fatp4) in endothelial cells, which is associated with a decrease in lipid droplets in the heart and skeletal muscle fibers (26) and improved sensitivity to Insulin has been implicated in diabetic models (27). Considering that the liver is also a metabolically active tissue, and on the other hand, it has been reported that regular exercise can increase the body's overall metabolism and, as a result, the liver's activity to finance long-term activities (28); Therefore, the increase of VEGF-β can be attributed to the improvement of mitochondrial activity in the liver in adaptation to regular exercise. Other results of the current research also showed that the use of atorvastatin increased the expression of the hepatic VEGF-β gene compared to the control diabetes group. Atorvastatin, an HMG-CoA reductase inhibitor, is widely used in the treatment of dyslipidemia (29). In a human study, atorvastatin 10 mg daily has been reported to be safe and effective in reducing the risk of first cardiovascular events, including stroke, in patients with type 2 diabetes without elevated LDL cholesterol (31). It can be said that part of these anti-diabetic effects of atorvastatin is related to the effects of this drug on improving fat metabolism in the liver.In the investigation of the interactive effect of interval training and atorvastatin consumption, the results of this research showed that in the interactive group, although a significant increase in the expression of the hepatic VEGF-β gene was observed compared to the control diabetes group, these changes were not compared to the diabetes + exercise and diabetes + groups. Atorvastatin was not significant; it seems that the combined use of exercise and atorvastatin does not have a greater advantage on hepatic VEGF-β gene expression than either method alone.

The reduced organ function following delayed nerve repair highlights the need for pharmacological interventions. In this regard, many chemical agents have been administered after nerve injury; however, their functional outcomes are not satisfying yet. The present study aimed to evaluate the effects of the administration of citicoline and atorvastatin on the regenerative capacity of the distal end of the transected sciatic nerve throughout a delayed nerve repair period.

The sciatic nerve of male rats (250-300 g) was transected, and the animals were intraperitoneally administrated citicoline (200 mg/kg, n=5), atorvastatin (5 mg/kg, n=5), citicoline + atorvastatin, and vehicles (control groups 1 and 2, n=5) for one month. In the sham group (n=5), the sciatic nerve was only exposed. After one month, the transected nerve was repaired. Fourteen weeks after surgical repair, morphometric and electron microscopic evaluations were performed on the nerve.

In the present study, improvement in the structural (fiber diameter, axon diameter, and myelin thickness, etc.) and ultrastructural (degree of myelin destruction) indices of the distal segment of the nerve was observed in the citicoline and atorvastatin groups compared to the control groups (P< 0.01). In addition, the nerve structural and ultrastructural indices in the citicoline + atorvastatin group were better than each citicoline and atorvastatin group.

The results of this study showed that the administration of citicoline and atorvastatin leads to maintaining the regeneration capacity of the distal part of the nerve in the condition of delayed nerve repair

One of the possible mechanisms for resistance to insulin and type 2 diabetes is dysfunction and impaired mitochondrial biogenesis. Mitochondrial density and function are associated with cardiovascular disease, sarcopenia, insulin resistance and type 2 diabetes, the aging process, and aerobic capacity. Today, a complete understanding of mitochondrial biogenesis is associated with an understanding of various cellular pathological conditions. Mitochondria play a role in increasing mitochondrial function. Quality, mitochondria represent an improvement in mitochondrial biogenesis. In tissues with high oxidative capacity, such as skeletal muscle, activated by gamma receptor joint proliferator, an alpha activated by peroxisome proliferator (AMPK) is considered to be the most important regulator of biogenesis and mitochondrial function. (cytochrome C and AMPK) is a transcription and replication agent for mitochondrial DNA and plays an important role in mitochondrial biogenesis processes. A study by Madrasa (2018) showed that decreased expression of this group of genes is associated with decreased capacity, whole body aerobics in patients with type 2 diabetes and decreased expression of PGC-1α and nuclear genes encoding mitochondria in individuals. Insulin resistance can mean that these people have low levels of aerobic exercise. Exercise can play an important role in accelerating mitochondrial biogenesis, possibly leading to a reduction in mitochondrial dysfunction that occurs during the aging process, metabolic diseases such as type 2 diabetes, and conditions of muscle inactivity resisting fatigue and increasing the quality of life. The method of training is in the form the although metabolic control is available in type2 diabetes effect of aerobic exercise and the chemical drug atrostatin on the expression of genes affecting the mitochondrial biogenesis of cardio myositis in samples with type 2 diabetes has not been studied and because of its importance in controlling mitochondrial function following diabetes. Type 2 is impaired, it is necessary to study it, so the aim of the present study was to investigate the protective effect of continuous and intermittent exercise with atrostatin on some markers of mitochondrial biogenesis signaling myositis (cytochrome C and AMPK) in diabetic elderly rats.

 Thirty-five male rats (20 weeks old) weighing between 300 and 350 g were randomly divided into 7 groups. Diabetes was induced in 6 groups. To make diabetic mice, streptozotocin (STZ) was injected intraperitoneally at a dose of 50 mg per kg body weight (26). Atorvastatin was taken orally after a meal at a dose of 2 mg per kg body weight .The first week of continuous training program at a speed of 15 meters per minute for five minutes, the rats started running on the treadmill. Then, every week, increasing the speed by 1 to 2 meters per minute for 1 to 2 minutes increases the running time. The number of continuous training sessions was five times a week. The interval training program consisted of 25-25 minutes of treadmill running on a treadmill at a speed of 15 meters per minute for the first week, with one meter per minute added each week to 22 meters per minute in the eighth week. The duration of the first session was 25 minutes, with one minute added to each session, reaching 64 minutes in the eighth week.48 hours after the last training session with 10 to 12 hours of night fasting, intraperitoneal injection of a combination of ketamine and xylazine was performed in anesthetized mice and tissue samples were taken. Their heart tissue was isolated and stored at -80 ° C and then transferred to a laboratory for genetic testing. To investigate the significant changes in each of the research changes between different groups, one-way analysis of variance was used and if a statistically significant difference was observed to determine the location of ANOVA, Tukey post hoc test was used. Significance level P <0.05 was considered for all calculations.

In the present study, the effect of continuous and intermittent exercise combined with atorvastatin administration (cytochrome C and AMPK)  gene expression in cardiac myocytes of elderly diabetic rats was investigated. The first finding of the present study showed that the expression of (cytochrome C and AMPK) gene in cardiac myocytes of rats with type 2 diabetes was significantly reduced compared to the healthy control group, while after 8 weeks of intervention, the mean (cytochrome C and AMPK) to Significantly decreased compared to the healthy control group, while after 8 weeks of intervention, the mean (cytochrome C and AMPK) increased in the exercise and atorvastatin groups, but in the combined intervention group, this increase was significantly greater. It seems that taking atorvastatin with 8 weeks of continuous and intermittent physical activity has been able to make changes beyond taking atorvastatin alone or continuous and intermittent exercise. In this regard, Baghdam et al. (2019) by examining the effect of 8 weeks of aerobic exercise on the expression of PGC-lα gene in heart tissue in diabetic rats, concluded that aerobic exercise significantly increases the concentration of PGC-lα in heart tissue ( 29). However, in contrast to the findings of Chavanel et al. (2017) showed that exercise has no significant effect on the level of PGC-1α mRNA or other mitochondrial biogenesis regulators such as (cytochrome C and AMPK) (30). One of the most important reasons for inconsistency in Chavanel research with the results of the present study may be the age, sex and race of the subjects as well as the type of training protocol. (cytochrome C and AMPK) is one of the most important transcriptional coordinator coagulators that positively regulates the expression of genes associated with metabolic and mitochondrial adaptations, thus influencing cardiac substrate selection, mitochondrial function, ATP production capacity, and species production. Reacts to oxygen (ROS). Physical activity is one of the factors that trigger these messaging pathways. In other words, mitochondrial biogenesis in the cell is induced by environmental stimuli such as physical activity.Another result of the present study was the decrease in (cytochrome C and AMPK)  gene expression in cardiac myocytes of elderly diabetic rats compared to the healthy control group, while after 8 weeks of intervention, a significant increase in (cytochrome C and AMPK)  gene expression was observed in atorvastatin and combination groups compared to the patient group. This increase was greater in the combination of diabetic + atorvastatin + periodic exercise. It seems that when the volume of training is the same, the intensity of training can be an effective factor in the expression of (cytochrome C and AMPK); Therefore, this study showed that with a constant volume of periodic training is more effective than continuous training in the expression of (cytochrome C and AMPK) gene. The present study showed that intermittent and continuous exercise with atorvastatin increased (cytochrome C and AMPK)  in the heart cells of elderly diabetic rats, which decreased due to diabetes and aging. Consistent with the results of the present study, Popo et al. Examined the effect of two months of aerobic exercise on skeletal muscle TFAM in human diabetic specimens and reported a significant increase. Therefore, the effect of the training period is enhanced at higher intensities. Exercise frequency is also one of the effective factors in increasing mitochondrial biogenesis. Chavanel et al. (2017) have shown that exercise has no significant effect on the level of mRNAPGC-1α or other mitochondrial biogenesis regulators including TFAM and cytochrome C and AMPK. One of the most important reasons for inconsistency in Chavanel research with the results of the present study may be in the condition of the subject and the type of muscle fiber as well as the type of training protocol. TFAM is a high-mobility transcription factor group responsible for replication and transcription of mitochondrial DNA. Impairment of the (cytochrome C and AMPK)  target specifically in cardiac tissue leads to a significant reduction in electron transport capacity, spontaneous cardiomyopathy, and heart failure. In contrast, increased TFAM expression in cardiac tissue protects against heart failure due to myocardial infarction.

Another finding of the present study was the positive and significant effect of atorvastatin on the expression of (cytochrome C and AMPK) genes in mice with type 2 diabetes. Studies show that atorvastatin improves mitochondrial function and prevents apoptosis in myocardial hypertrophy. In the present study, Chen et al. (2018) inhibited the decrease in the expression of (cytochrome C and AMPK) in mice with myocardial insufficiency by treatment with atorvastatin . According to the results obtained in the present study, the effects of atorvastatin may be fundamentally different in different patients and with different races, and also its effects may vary depending on the dose or duration of use and the type of statin used. However, the effect of co-administration of atorvastatin and exercise with (cytochrome C and AMPK) on cardiac tissue has not been investigated. Reduces oxidative stress and inflammation in a variety of metabolic syndrome diseases such as diabetes and therefore improves these diseases by inhibiting mitochondrial damage.The combined use of both has more effective therapeutic effects on type 2 diabetes. The results of this study on improving heart function have been confirmed by previous studies.

Cardiovascular diseases are the main cause of death worldwide. High cholesterol level is a risk factor for coronary artery disease. Cholesterol production is regulated by the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Statins, as the inhibitors of HMG-CoA reductase, are often used as cholesterol-lowering drugs to prevent cardiovascular diseases. This study aims to synthesize novel derivatives of atorvastatin and investigate their effect on liver and kidney serum parameters, function, and histology.

Atorvastatin derivatives named S1, S2, and S3 were synthesized by acylation of the benzene ring of atorvastatin. The effect of compound S3 on serum parameters related to liver and kidney function was evaluated in rabbits with a high-fat diet-induced hypercholesterolemia. SPSS software, version 20 was used to analyze the data using statistical tests.

The compound S3 increased high-density lipoprotein cholesterol and reduced total cholesterol, low-density lipoprotein, and triglyceride compared to the standard drug atorvastatin during 30 days of treatment (P<0.05). The liver enzymes were used to evaluate the toxicity of compound S3. In addition, the S3 compound significantly reduced the amount of urea, creatinine, and uric acid compared to the hyperlipidemic group. Histological study results showed that the compound S3 reduces tissue damage in hypercholesterolemic rabbits.

The S3 compound of atorvastatin can be considered as a cholesterol-lowering agent. This indicates that phenyl rings with higher electron density attached to propargyl show better inhibitory effects against ?? The S3 can be an effective drug for preventing atherosclerosis. However, more research is needed to clarify its exact mechanism.

Statins, which are primarily used for controlling blood cholesterol levels, have a well-known role in inhibiting the inflammatory process and reducing mortality rate of infectious diseases. This study aims to evaluate the effect of atorvastatin along with standard treatment protocol in hospitalized adults with COVID-19.

This randomized controlled clinical trial was conducted on adults hospitalized due to COVID-19 infection at Shahid Beheshti Hospital in Qom, Iran from April to September 2020.  They were randomly divided into groups of treatment (n=37, receiving atorvastatin 40 mg daily for 30 days plus standard treatment protocol) and control (n=37, receiving standard treatment protocol alone). The data were analyzed in SPSS v.22 software using chi-square, paired t-test, and ANOVA. P<0.05 was statistically significant.

The CRP level in the atorvastatin-treated group decreased significantly such that there was a significant difference between the two groups after 30 days (P=0.01). There was no significant difference in Spo2 level on the discharge day. The length of hospitalization in the atorvastatin-treated group was significantly reduced compared to the control group (P<0.05).

The use of atorvastatin as an adjunctive treatment method, can significantly reduce the length of hospitalization and CRP level after 30 days in hospitalized patients.