فهرست مطالب ahmad reza dehpour

Statins affect the bone metabolism. Considering the role of nitric oxide (NO) in many physiological processes, this study assessed the effects of atorvastatin (ATOR) and NO on the mandible and skull bone density (BD) in ovariectomized rats. This study evaluated 48 female Sprague-Dawley rats in 6 groups (n=8). Groups 1 and 2 underwent sham surgery. Group 1 (sham) did not receive any medication, but group 2 (sham/ATOR) received atorvastatin. Groups 3 to 6 underwent ovariectomy. Group 3 (OVX) did not receive any medication, group 4 (OVX/ATOR) received atorvastatin, group 5 (OVX/L-NAME) received L-NG-nitro arginine methyl ester (L-NAME), and group 6 (OVX/ATOR/L-NAME) received both atorvastatin and L-NAME. Atorvastatin (40 mg/kg) was gavaged and L-NAME (3 mg/kg) was administered intraperitoneally for 4 weeks. All rats underwent lateral cephalometry before and after the interventions, and BD was measured at 2 points in the mandible and skull before and after the intervention by a digital densitometer. Data were analyzed by t-test, ANOVA, and Sidak test (alpha=0.05). The change in BD was 26.5±10.17 in the mandible and 22.17±9.45 in the skull in OVX group. These values were 25.63±5.55 and 28±8.59 in OVX/ATR, 1.5±7.78 and -1.88±4.39 in OVX/L-NAME, and 6.63±7.37 and 4.33±6.35 in OVX/ATOR/L-NAME, respectively. OVX/ATOR showed no significant difference (P=1), but OVX/L-NAME (P<0.001) and OVX/ATOR/L-NAME (P<0.001) groups showed significant differences with OVX group. The present findings indicated that atorvastatin had no significant effect on BD, but administration of L-NAME prevented osteoporosis in ovariectomized rats.

Cirrhosis is the consequence of chronic liver injury Considering the crucial role of oxidative stress in the progression of liver cirrhosis, we aimed to investigate the ameliorative effect of NTX against oxidative stress in carbon tetrachloride (CCl4)-induced cirrhotic rats. Eighty-four male Wistar rats were randomly assigned into 4 groups (21 rats /group I) receiving CCl4; (II) NTX+CCl4; (III) mineral oil (M) (as the control); (IV) NTX+M. The animals in each group were sacrificed in 3 different time-points 2 weeks, 6 weeks (early cirrhosis) and 8 weeks (advanced cirrhosis). Liver function tests, NO metabolites, GSH level, as well as the activity of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxides (GPX), and hexokinase (HK) were assessed. NTX was able to ameliorate liver injury, revealed by attenuation of ALT activity, which was significantly enhanced due to cirrhosis induction, as well as pathological evaluation. HK was also increased significantly after treatment with CCl₄ while NTX moderated this increase. Although CCl4 treatment did not have a significant effect on GSH levels, NTX was able to considerably increase GSH in blood. The activity of CAT and SOD as well as NO levels were all augmented by NTX in CCl4-treated rats. Naltrexone demonstrates antioxidative effects in liver cirrhosis and may confer a protective effect against hepatic cirrhosis through modulation of oxidative stress.

In liver cirrhosis, there is low T3 syndrome associated with a decrease in total triiodothyronine (T3) and free T3 concentrations and cirrhotic cardiomyopathy (CCM) with chronotropic incompetence. Thus, we aimed to investigate the effects of eliminating T3 and thyroxine (T4) deficiencies on cardiac chronotropic dysfunction. Bile duct ligation (BDL) was used to induce cirrhosis in male Wistar rats. The chronotropic responses were studied through the Power Lab system in sham/saline, sham/T3T4, BDL/saline, and BDL/T3T4 groups. The serum T3 and T4, and T3 resin uptake (T3RU) levels were assessed. The atrial T3 receptor expression was investigated through a real-time polymerase chain reaction (Real-time PCR). The chronotropic responses were decreased in the BDL/saline group and raised in the BDL/T3T4 group. The serum T3 levels decreased in the BDL/saline group compared to sham group, but increased in the BDL/T3T4 group compared to the BDL/saline group. The serum T4 level increased in the BDL/saline and decreased in the BDL/T3T4 group. The serum T3RU level decreased in the BDL/saline and increased in the BDL/T3T4 group. The T3 receptor expression in atria increased in the BDL/saline group, nonetheless, it did not change in the BDL/T3T4 group compared to the sham/saline and the BDL/saline groups. T3T4 treatment did not increase the chronotropic response in the control group but the treatment improved the chronotropic hyporesponsiveness, and serum T4 and T3 RU abnormalities in cirrhosis, however, it is not related to the atrial T3 receptor expression.

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) and its cause is unknown. Several environmental and genetic factors may have roles in the pathogenesis of MS. The synthesis of solid lipid nanoparticles (SLNs) for ivermectin (IVM) loading was performed to increase its efficiency and bioavailability and evaluate its ability in improving the behavioral and histopathological changes induced by cuprizone (CPZ) in the male C57BL/6 mice.    Four groups of 7 adult C57BL/6 mice including control (normal diet), CPZ, IVM, and nano-IVM groups were chosen. After synthesis of nano-ivermectin, demyelination was induced by adding 0.2% CPZ to animal feed for 6 weeks. IVM and nano-IVM (1 mg/kg/day, IP) were given for the final 14 days of the study. At last, behavioral tests, histochemical assays, and immunohistochemistry of TRPA1, NF-kB p65, and GFAP were done. The time of immobility of mice in the IVM and nano-IVM groups was reduced compared to the CPZ group. Histopathological examination revealed demyelination in the CPZ group, which was ameliorated by IVM and nano-IVM administration. In IVM and nano-IVM groups corpus callosum levels of TRPA1, NF-kB p65, and GFAP were decreased compared to the CPZ group. In the IVM and nano-IVM groups, the levels of MBP were significantly higher than in the CPZ group.  The results evidenced that IVM and nano-IVM administration is capable of reducing demyelination in mice.

Cirrhotic patients have hyperdynamic circulation and at-rest tachycardia, and agents that activate the sympathetic pathway, such as physical practice and pharmacologic stimulations, compared with the normal population, cannot cause enough increase in heartbeat, a condition known as cirrhotic cardiomyopathy. Concerning the presentation of 5-HT2 & 5-HT3 receptors in rat hearts, we used Ketanserin as a 5-HT2 receptor inhibitor & Tropisetron as a 5-HT3 receptor inhibitor to evaluate chronic therapeutic effects of 5-HT2 & 5-HT3 antagonists on the cardiac chronotropic response of cirrhotic rats to adrenergics. Cirrhosis was induced by surgical ligation of the bile duct in Male Wistar rats, and another group remained sham. A week after bile duct ligation or sham surgery, the subjects were given an intraperitoneal injection of either saline or Tropisetron (2 mg/kg). In other BDL & Sharm groups, the subjects were given an intraperitoneal injection of either saline or Ketanserin (6 mg/kg) every other 3 days in the last 3 weeks. Four weeks after bile duct ligation or sham surgery, the atria were isolated and chronotropic responsiveness to Isoproterenol was assessed using a standard organ bath. Our data showed that chronic treatment with Tropisetron (5-HT3 antagonist) in cirrhotic rats could decrease the cardiac chronotropic response. Chronic treatment with Tropisetron can cause a significant decrease in cardiac chronotropic response to Isoproterenol in healthy and cirrhotic rats, even lower than that in cirrhotic rats (without any special treatment). Chronic treatment with Ketanserin cannot change their impaired chronotropic response to Isoproterenol.

Renin-angiotensin system (RAS) components such as angiotensin II, angiotensin receptors (AT1R and AT2R), and angiotensin-converting enzyme (ACE) are expressed in different cell types of the skin. Through AT1R, angiotensin II increases proinflammatory cytokines contributing to fibrosis, angiogenesis, proliferation, and migration of immune cells to the skin. In contrast, AT2R suppresses the effects mentioned above. Many studies show that angiotensin receptor blockers (ARBs) and angiotensin-converting enzymes (ACEi) reduce the proinflammatory cytokines and fibrogenic factors including transforming growth factor β (TGF-β), Connective tissue growth factor (CTGF), and IL-6. This review article provides a detailed research study on the implications of ARBs in wound healing, hypertrophic scar, and keloids. We further discuss the therapeutic potentials of ARBs in autoimmune and autoinflammatory skin diseases and cancer, given their anti-fibrotic and anti-inflammatory effects.

Among the many types of central nervous system (CNS) disorders, seizures and epilepsy severely affect the quality of life and routine daily activity of the sufferers. We aimed to review research studies that investigated the effect of statins on the prevention and treatment of seizures and epilepsy. Both animal models and human studies were included in this review. This article starts with a brief introduction about seizure, its prevalence, treatment, and various animal models of seizures and epilepsy. Next, we discuss statin’s mechanism of action, side effects, and effects on neurological disorders with a specific focus on seizures. Finally, the effects of different types of statins on seizures are compared. The present review gives a better understanding of the therapeutic effects of statins on neurological disorders in animal models and human studies. This permits researchers to set up study designs to resolve current ambiguities and contradictions on the beneficial effects of statins on neurological disorders.

Accidental or intentional poisoning with Aluminum phosphide (AlP) is associated with severe complications such as metabolic acidosis, cardiac failure, and death. Previous animal experiments demonstrated that fresh-packed RBC is protective in an experimental model of AlP poisoning. The aim of this study was to assess the effect of fresh-packed RBC on survival in patients admitted to a referral hospital due to AlP poisoning in a randomized clinical trial. Eighty-two patients were admitted to Clinical Toxicology Unit at Baharloo Hospital due to acute AlP poisoning after approval by the Iranian Registry of Clinical Trials (registration reference: IRCT20180428039443N1). All patients received standard treatment, and forty-one of them received fresh-packed RBC. There was no significant difference between groups in the underlying characteristics, including vital signs and laboratory investigations. But interestingly, the mortality rate was meaningfully decreased (difference: 31.7%, 95% CI: 0.10-0.52) in patients receiving fresh-packed RBC (10 deaths/31 survived; 24.4% mortality) in comparison to standard treatment patients (23 deaths/18 survived; 56.1% mortality). Furthermore, fresh-packed RBC substantially improved the GCS, systolic/diastolic blood pressure, ST changes, and pH 12- and- 24 hours after admission. This study showed that fresh-packed RBC infusion alongside standard supportive treatment leads to a decrease in mortality rate; also, it provided evidence for a protective role of fresh-packed RBC in the management of patients with acute AlP poisoning.

Macrophages and glial activation contribute to the pathophysiology of spinal cord injury (SCI). Some preclinical studies have shown the anti-inflammatory effects of aripiprazole (ARP). In the current study, we evaluated the anti-inflammatory effects of ARP in a rat SCI model. Forty male Wistar rats underwent either T9 vertebra laminectomy or were used as a sham-operated group without laminectomy. There were four major groups in this study: a sham-operated, three treatments (normal saline [vehicle] control versus ARP 10 and 20 mg/kg/day for three days after surgery, first dose 30 minutes post-surgery) SCI groups. We evaluated locomotor scaling and neuropathic pain behavioral tests over 28 days. On Day 28, tissue samples were investigated for neuroinflammatory and histopathology changes through flow cytometry and ELISA. ARP (10 and 20 mg/kg/day, 3 days) treatment significantly reduced locomotors disability (P<0.01) and mechanical (P<0.01) and thermal allodynia (P<0.001) scores. Additionally, Levels of tumor necrosis factor (TNF)-α level and interleukin (IL)-10 were significantly altered in ARP-treated spinal cord tissues 28 days after SCI (P<0.01). Moreover, spinal cord tissue expression of M1 and M2 macrophages, as well as M1/M2 ratio, were reduced in ARP-treated SCI animals, concurrent with decreased M1 and increased M2 and M1/M2 in dorsal root ganglion (P<0.001). Our study indicates that ARP has therapeutic effects on SCI via the reduction of neuroinflammation and SCI sensory and locomotor abnormalities.

Multiple Sclerosis (MS) is an inflammatory disorder wherein the myelin of nerve cells in the central nervous system is damaged. In the current study, we assessed the effect of Dapsone (DAP) on the improvement of behavioral dysfunction and preservation of myelin in the cuprizone (CPZ) induced demyelination model via targeting Nrf2 and IKB.  MS was induced in C57BL/6 mice through diet supplementation of CPZ (0.2%) for 6 weeks, and DAP (12.5 mg/kg/day; IP) was administered for the last 2 weeks of treatment. Pole test and rotarod performance test, LFB and H&E staining, and Immunohistochemistry (IHC) staining of p-Nrf2 and p-IKB were performed. Furthermore, superoxide dismutase (SOD) and nitrite were measured. DAP treatment prevented body loss induced by CPZ (P<0.001). Pole test showed that CPZ increased latency time to fall (P<0.0001) but the latency to reach the floor in the DAP-CPZ group was significantly shorter (P<0.0001). Rotarod performance test showed the effect of CPZ in reducing fall time in the CPZ group (P<0.0014); however, DAP significantly increased fall time (P=0.0012). In LFB staining, DAP reduced demyelination induced by CPZ. CPZ significantly decreased p-Nrf2 and elevated p-IKB levels compared with the control group (P<0.0001), but in DAP-treated groups markedly modified these changes (P<0.0001). CPZ increased the brain nitrite levels and reduced SOD activity, but in DAP-treated considerably reversed CPZ-induced changes.  These data support the suggestion that the beneficial properties of DAP on the CPZ-induced demyelination are mediated by targeting Nrf2 and NF-kB pathways.

Epilepsy is one of the most common neurological disorders. Though there are several effective drugs for treating epilepsy, most drugs are associated with side effects and drug interactions. Stachys lavandulifolia used in Iranian traditional medicine has proven anti-anxiety and sedative properties. The current study aimed to evaluate the anticonvulsant effect of hydroalcoholic extract of S. lavandulifoliaon the Pentylenetetrazole (PTZ)-induced seizure in male mice and the role of benzodiazepine and opioid receptors. 

This study was conducted on 100 male mice, randomly categorized into 10 groups: Normal Saline (NS), two diazepam groups (0.025 and 0.1 mg/kg), three S. lavandulifolia extract groups (50, 100, and 200 mg/kg), diazepam 0.025 mg/kg+S. lavandulifolia extract 50 mg/kg, and three groups that pretreated with NS, flumazenil, or naloxone, 5 min before injection of 200 mg/kg S. lavandulifolia extract. After 30 min, PTZ (80 mg/kg) was injected into animals, and seizure indices were evaluated. 

The S. lavandulifoliaextract attenuated the PTZ-induced seizures in a dose-dependent manner, and pretreatment with flumazenil reversed this effect. However, pretreatment with naloxone could not reverse this effect because seizure indices in the naloxone pretreated group were lower than that in the normal saline group. The combination of an ineffective dose of diazepam and S. lavandulifoliaextract decreased PTZ-induced seizures. 

The results of our study showed the anticonvulsant properties of hydroalcoholic extract of S. lavandulifolia. These effects might be due to the impact of the components of this extract on the central benzodiazepine system.

Accumulating evidence suggests the potential use of chloroquine, an anti-malaria medication, as a neuroprotective agent. Moreover, several studies have reported that the endogenous opioids and nitric oxide (NO) may mediate the chloroquine’s effects. In the present study, effects of chloroquine on hyoscine-induced memory impairment were assessed. Furthermore, the possible involvements of opioids and NO were evaluated. Chloroquine was administered intraperitonially (i.p.) at doses of 0.1, 0.5, 1, 3, 10, and 20 mg/kg to hyoscine-treated (1mg/kg, i.p.) mice, and the spatial and fear memories were evaluated using Y-maze and passive-avoidance tasks, respectively. Also, to provide further evidence about chloroquine’s mechanism of action, the opioid receptors and the NO production were blocked using two nonselective antagonist’s naltrexone and L-NAME, respectively. Chloroquine at doses of  0.5, 10 and 20 mg/kg furtherly damaged the impaired memory of hyoscine-treated mice and at doses of 10 and 20 mg/kg impaired the memory of saline-treated mice in the passive-avoidance task. Additionally, chloroquine at doses of 0.5 and 1 mg/kg improved the spatial memory in hyoscine-treated mice in Y-maze test. In addition, naltrexone (3 mg/kg) reversed the neuroprotective effect of chloroquine (1 mg/kg) in hyoscine-treated mice in Y-maze task. It could be concluded that chloroquine at low doses may improve cognitive performances by involving the opioid receptors; as a result, blocking the opioid receptors may reverse chloroquine’s neuroprotective effect. Notably, chloroquine at high doses did not improve the memory and in combination with hyoscine, it caused even more damage to the long-term memory.

Exogenous electrical stimulation of the skin may mimic its endogenous bioelectric currents. In this study, a combination of direct current (DC) and magnetic field (MF) was investigated in an excision wound model in rats.

A circular wound was created on the posterior of the neck, and an electrode was fixed in the wound center. Rats were divided into sham, DC (600 µA), MF (~0.8 T), and magnet-direct current (MDC) groups. The study was conducted in 14 days with 20-min treatment daily.

The DC and MDC groups had higher healing percentages (P < 0.01) with mean differences of -13.42 and -15.63, respectively. Direct current on days 2, 5, and 6, and MDC on days 8, 9, 10, 11, 12, and 13 showed higher wound closing. In the DC-treated group, angiogenesis was improved on day 7. In MDC-treated rats, angiogenesis and fibroplasia were improved on day 13. The MF and MDC groups had lower granulation thicknesses on day 7. Granulation thickness increased on day 13 in the MF and MDC groups, while it decreased in the DC group. Direct current treatment improved healing in the first half of the study period, whereas MDC enhanced it in the second half, overtaking DC. From day 7, the magnet group's healing started to overtake the control group slightly in the last four days.

To accelerate wound healing, we suggest applying DC in the first days of wounding and MDC in the following days.

Salvia reuterana, commonly known as Maryam Goli Esfahani, is a member of the Labiateae family. In Iranian folk medicine, aerial parts of S. reuterana have been used as sedative and anxiety. Evaluation of various extracts of the plant for their analgesic activity revealed that treatment of mice with n-hexane extract (500 mg/kg, i.p.) significantly increased the latency time as compared to the control group. Fractionation of the hexane extract of S. reuterana led to the isolation of sclareol as the main compound (0.19% w/w). Column chromatography was used to isolation of compounds from S. reuterana and spectroscopic method including NMR was used to identification of the isolated compound. Evaluation the analgesic effect of sclareol using hot plate, tail flick and formalin tests in mice confirmed the potent analgesic effect of sclareol as an effective compound of S. reuterana. These results showed that the n-hexane extract of aerial parts of S. reuterana and its main constituent sclareol showed significant analgesic activity in different rodent nociceptive behavioral tests.

Status epilepticus is a severe neurological disorder that can be life-threatening. Thalidomide and its analogs have shown promising results to confront pentylenetetrazole-induced seizures. This study aimed to evaluate the potential effects of three synthesized thalidomide derivatives on lithiumpilocarpine-induced status epilepticus.

To induce status epilepticus, rats received lithium chloride (127 mg/kg, i.p.) and pilocarpine HCl (60 mg/kg, i.p.) 20 h after lithium chloride injection. Thirty min before pilocarpine HCl administration, rats received hyoscine N-butyl bromide (1 mg/kg, i.p.) and concurrently one of the test compounds (5B, 5C, and 5D), diazepam, thalidomide, or vehicle (4% DMSO) to evaluate their anti-epileptic effects. Epileptic seizures scores were assessed through the Racine scale. Twenty-four h after injection of pilocarpine, brain samples were extracted for further histopathological evaluation.

Results revealed that among tested compounds (5B, 5C, and 5D), only compound 5C (1 mg/kg) exhibited excellent anti-epileptic activity comparable to diazepam (10 mg/kg). Compound 5D (100 mg/kg) only demonstrated comparable anti-epileptic activity to thalidomide (1 mg/kg). Compound 5B did not have any anti-epileptic activity even at the dose of 100 mg/kg. The histopathological survey showed that compound 5C has more neuroprotective effects than diazepam and thalidomide in the cortex of the brain. In the cornu ammonis 1 region, thalidomide had higher protective properties and in the cornu ammonis 3 and dentate gyrus areas, diazepam had higher efficacy to prevent necrosis.

Compound 5C is a good candidate for further studies regarding its potency, compared to thalidomide and diazepam.

The clinical use of doxorubicin as a potent chemotherapeutic agent is limited due to its dose-dependent cardiotoxicity. Oxidative stress and inflammatory pathways have a pivotal role in doxorubicin-induced cardiotoxicity. Sumatriptan, a 5-hydroxytryptamine (5-HT)1B/1D agonist that is mainly used to relieve migraine pain, has suggested exerting protective effects in numerous pathological conditions through antiinflammatory properties. The aim of the present study was to investigate the effects of sumatriptan on doxorubicin-induced cardiotoxicity and the contribution of anti-inflammation and antioxidative responses. Cardiotoxicity was induced by the administration of doxorubicin three times a week (2.5 mg/kg i.p) for two consecutive weeks on male rats. The animals were divided into four groups, including Control, Sumatriptan (0.1 mg/kg) received group, doxorubicin received group, and Doxorubicin+Sumatriptan (0.1 mg/kg) received group. Sumatriptan was administered 30 min before every injection of doxorubicin. On the last day of the second week, the body weight, mortality rate, electrocardiogram (ECG) and histopathological changes, cardiac inotropic study, and biochemical factors were evaluated. The loss of body weight, mortality rate, ECG parameters, reduction of papillary muscle contractility force as well as histopathological scores following administration of doxorubicin indicated severe cardiac damage. However, treatment with sumatriptan inhibited the functional and structural impairment induced by doxorubicin. In addition, sumatriptan could significantly reduce cardiac tissue levels of malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α), which were increased in the doxorubicin-treated rats. This study illustrated the protective effects of sumatriptan on decreasing doxorubicin-induced cardiac toxicity and mortality rate in part through inhibition of inflammatory and oxidative stress pathways.

Atorvastatin exerts neuroprotective effects on the treatment of central nervous system disorders. Morphine analgesic tolerance and dependence remain as major concerns in medicine. Nitric oxide (NO) pathway mediates the development of opioid analgesic tolerance and dependence, as well as atorvastatin neuroprotection.

The present study aimed to assess the possible involvement of the NO/cGMP pathway in the process of the effects of atorvastatin on morphine physical dependence.

Dependence was induced by repetitive injection of morphine sulfate. Naloxone was injected at the dose of 4 mg/kg on the last day of the experiment to assess withdrawal signs. Animals received atorvastatin (1, 5, 10, and 20 mg/kg, orally). Nitric oxide synthase (NOS) inhibitors and ODQ were injected before protective dose of atorvastatin. The gene expression of NOS isoforms was evaluated by real-time PCR. Thereafter, the hippocampal levels of cGMP and nitrite were measured.

Treatment with atorvastatin 10 mg/kg significantly attenuated naloxone-induced withdrawal behaviours. The administration of L-NAME, aminoguanidine, and ODQ before atorvastatin enhanced its effects. The treatment with atorvastatin significantly decreased the nitrite and cGMP levels as well as NOS gene expression in the hippocampus of dependent animals.

It can be concluded that atorvastatin, possibly, through inducible NOS, could alleviate morphine dependence and withdrawal signs.

The aim of this study was to evaluate the anti-inflammatory effect of B. persicum essential oil on colonic inflammation and the role of suppression of NF-κB pathway in rat colitis induced by acetic acid solution. Induction of acute colitis was done by intra-luminal instillation of 2 ml of acetic acid (4%) diluted in normal saline. Two hours after colitis induction, 0.2% tween 80 in normal saline, prednisolone (4 mg/kg) or B. persicum essential oil (100, 200, and 400 mg/kg) were administered to the rats orally and continued for 5 consecutive days. The severity of macroscopic and microscopic damages was assessed. Myeloperoxidase and TNF-α activity was evaluated by biochemical analysis and ELISA respectively and protein expression of p-NF-κB was assessed by immunohistochemistry (IHC). Prednisolone and B. persicum essential oil (100, 200, and 400 mg/kg) decreased macroscopic and microscopic injuries compared to the acetic acid group. On the other hand, prednisolone and B. persicum essential oil (200 and 400 mg/kg) decreased the activity of MPO and TNF-α in the colon tissue of rats compared with the acetic acid group. Furthermore, they suppressed the expression of p-NF-κB protein induced by acetic acid administration. It is suggested that the anti-inflammatory effect of B. persicum essential oil on acetic acid-induced colitis in rats may be due to the suppression of NF-κB pathway.

Several factors contribute to the development of gastric erosions, including corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, and stress. These factors can cause or worsen gastrointestinal ulcers by activating inflammatory pathways or by altering gastric mucosal blood flow. Dapsone is an antimicrobial compound with anti-inflammatory properties. The aim of this study was to evaluate the protective effects of dapsone against gastric erosions-induced by alcohol, stress, or indomethacin. Gastric damage was induced in male rats in different three experimental models:  ethanol (5 ml/kg, p.o.)-, water-immersion stress-, and indomethacin (30 mg/kg, p.o.)- induced ulcer. Rats in each of these three experimental models were divided into 5 groups: Normal group, 2. Control group (gastric damage + vehicle), 3. Gastric damage+ dapsone 1 mg/kg, 4. Gastric damage+ dapsone 3 mg/kg, 5. Gastric damage+ dapsone 10 mg/kg. In this study, the J- score ulcer index and histopathological assessment were performed. In addition, inflammatory cytokines levels, NF-κB expression and MPO activity were determined. Dapsone reduced the tissue injuries and erosion area in all three experimental groups compared to the control group. In addition, serum levels of inflammatory cytokines, TNF-alpha and IL-1β were reduced in the dapsone treatment groups. The expression of NF-κB and tissue concentration of myeloperoxidase (a marker of neutrophil activation) was also reduced in rats given dapsone. To conclude, dapsone exhibits significant protective effects against the development of experimental gastric erosions in rats and these effects seem to be related to its anti-inflammatory and antioxidant properties.

Although pain is one of the most common symptoms of diseases, it is often mismanaged due to limited access to painkillers and ineffectiveness, unacceptable side effects, or the possibility of abuse. However, an alternative approach to existing analgesics is to indirectly increase endogenous pain relief pathways by neprilysin (an enkephalinase) inhibitors. This enzyme breaks down and inactivates enkephalin, dynorphin, endorphins, and their derivatives.

In this project, a new series of racecadotril-tetrazole-amino acid derivatives 15a-l was synthesized and characterized on the basis of IR, 1H and 13C NMR, mass spectrometry, and elemental analysis. The antinociceptive activity of synthesized compounds was assessed by a hot plate, tail-flick, and formalin assays in mice. Docking was used to identify the possible interactions between neprilysin and synthesized compounds.

Most of the synthesized compounds showed moderate to good analgesic effects in hot plat and tail-flick test in comparison to morphine and racecadotril. Compounds 15l and 15j were the most potent compounds. The synergistic analgesic effect of compounds 15l and 15j with morphine and the antagonistic effect of naloxone on the activity of these compounds confirm that the analgesic effect of compounds 15l and 15j could be mediated through the opioidergic system. The negative and high binding energy of docking simulation of the most potent compounds in the catalytic site of neprilysin was also in good agreement with the inhibitory activity of test compounds.

Racecadotril-tetrazole-amino acid derivatives, as potential antinociceptive agents, demonstrated moderate to good antinociceptive activities comparable with morphine and higher than racecadotril.

Drug-induced cholestasis is the main type of liver disorder accompanied by high morbidity and mortality. Evidence for the role of hepatobiliary pumps in the cholestasis patho-mechanism is constantly increasing. Recognition of the interactions of chemical agents with these transporters at the initial phases of drug discovery can help develop new drug candidates with low cholestasis potential. This review delivers an outline of the role of these transport proteins in bile creation. It addresses the pathophysiological mechanism for drug-induced cholestasis. In-vitro models, including cell-based and membrane-based approaches and In-vivo models such as genetic knockout animals, are considered. The benefits and restrictions of each model are discussed in this review. Current understandings into the cellular and molecular process that control the activity of hepatobiliary pumps have directed to a better understanding of the pathophysiology of drug-induced cholestasis. A combination of in-vitro monitoring for transport interaction, in-silico predicting systems, and consideration of and metabolic and physicochemical properties must cause more effective monitoring of possible liver problems.

The most important side effect after non-surgery cancer treatment (NSCT) is oral mucositis (OM) which degrades the quality of life. Using photobiomodulation (PBM), formerly known as low-level laser therapy (LLLT), in the prevention of NSCT-induced OM was widely studied. Hence, this review evaluates the efficacy of optical treatment parameters behind the working process of PBM in preventing NSCT-induced OM in preclinical studies.

Using the PubMed, Scopus and Embase databases, the present study systematically reviewed existing preclinical studies for optical treatment parameters of PBM in preventing NSCT-induced OM in experimental models without restriction on the year of publication.

In total, 51 articles were recognized during the search of the literature, and only 16 research papers were included in this review, taking into consideration the inclusion as well as exclusion benchmarks. The reviewed studies showed that a consensus has yet to be reached on the optimal PBM treatment parameters in preventing NSCT-induced OM. However, a wavelength of 660 nm, a power density of 40 mW as well as fluence which ranged between 2 and 6 J/cm2 were mostly utilized in the included studies. Furthermore, the severity of NSCT-induced OM was reduced following PBM application with no reported severe side effects.

The efficacy of PBM with the associated optical parameters is a promising strategy in preventing NSCT-induced OM. However, the optimal parameters of PBM need to be investigated.

Epileptic seizure is phenomenon of abnormal synchronous neuronal discharge of a set of neurons in brain as a result of neuronal excitation. Evidence shows the nitric oxide (NO) involvement in neuronal excitability. Moreover, the role of NO-mediated cyclic guanosine monophosphate (cGMP) activation in seizure pathogenesis is well-established. Sumatriptan is a selective agonist of 5-Hydroxytryptamine1B/D auto-receptor, has been reassessed for its neuroprotection. This study was aimed to explore the anticonvulsant effect of sumatriptan through possible involvement of NO-cGMP pathway in mice. For this purpose, the protective effect of sumatriptan on PTZ-induced clonic seizure threshold (CST) was measured using NO-cGMP pathway inhibitors including N(G)-nitro-L-arginine (L-NNA, 1, 5, and 10 mg/kg), 7-nitroindazole (7-NI, 30, 45, and 60 mg/kg), aminoguanidine (AG, 30, 50, and 100 mg/kg), methylene blue (MB, 0.1, 0.5, and 1 mg/kg) and sildenafil (5, 10, and 20 mg/kg). The involvement of nitrergic system was further confirmed by measurement of nitrite levels by Griess reaction. The gene expression of neuronal nitric oxide synthase (nNOS) and subunits of soluble guanylyl cyclase (sGC) was studied using qRT-PCR analysis. Acute administration of sumatriptan (1.2 and 0.3 mg/kg) in combination with subeffective doses of NOS, sGC, and phosphodiesterase 5 inhibitors significantly reversed the PTZ-induced CST (P≤0.001). The nitrite level in prefrontal cortex was significantly attenuated by sumatriptan (P≤0.01). Furthermore, sumatriptan downregulated the PTZ-induced mRNA expression of nNOS, and α1, α2, and β1 genes in cerebral cortex of mice (P≤0.0001). In conclusion, the anticonvulsant activity of sumatriptan at least, in part, is mediated through inhibiting NO-cGMP pathway.