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BACKGROUND AND OBJECTIVE: Gentamicin is one of the aminoglycoside antibiotics that commonly causes nephrotoxicity. Antioxidants are effective in reducing gentamicin-induced nephrotoxicity. In this study, we investigated the possible effect of L-Glutamine on the reduction of renal tissue damages and renal function recovery in gentamicininduced nephrotoxicity in rats. METHODS: In this experimental study, 32 rats were divided into four groups of eight: Sham group, Gentamicin group (100 mg/kg i.p for 12 days), L-Glutamine group (30 mg/kg by gavage for 12 days), Gentamicin+L-Glutamine group. Then through anesthesia, the blood sample was collected via cardiac and its serum was used to measure the BUN and creatinine levels. The kidney of the rat was used to measure malondialdehyde (MDA), glutathione peroxidase (GPX), catalase (CAT), glutathione (GSH) and determine histopathological parameters. FINDINGS: Receiving gentamicin causes significant elevation in BUN, Creatinine, MDA of the kidney, tubular necrosis, eosinophilic cast, and leukocyte infiltration compared to sham group (p<0.05). CAT, GPX, and GSH in gentamicin group caused significant decrease compared to the sham group (p<0.05). Glutamine has significantly decreased the MDA level, and leukocyte infiltration compared to gentamicin group (p<0.05). Glutamine caused significant increase in GPX (CAT in group 4) compared to gentamicin group (p<0.05) and in group 3, BUN, tubular necrosis, eosinophilic caused significant decreases compared to gentamicin group (p<0.05). CONCLUSION: Receiving L-Glutamine, 30 mg/kg orally for 12 days has an effective role in the reduction of kidney injuries induced by gentamicin. [ABSTRACT FROM AUTHOR]

Objective: The leukotrienes are inflammatory mediators. In the present study, the analgesic role of local montelukast, a cysteinyl leukotriene receptor antagonist, and the possible involvement of L-arginine/NO/cGMP/K ATP channel pathway and PPARγ receptors was assessed in the formalin test in rats., Methods and Results: The local administration of montelukast into the hind paw produced dose-related analgesia during both phases of the formalin test. Furthermore, pre-treatment with L-NAME, methylene blue, and glibenclamide prevented montelukast (10 μg/paw)-induced antinociception in both early and late phases of the test. Moreover, the local L-arginine and diazoxide before the sub-effective dose of montelukast (3 μg/paw) produced an analgesic effect. Also, local GW-9662 blocked antinociception induced by montelukast plus pioglitazone (10 μg/paw)., Conclusion: In conclusion, montelukast produced peripheral analgesia through PPARγ receptors and activation of the L-arginine/NO/cGMP/K ATP channel pathway, with potential for a new topical analgesic drug.

Introduction: Methotrexate (MTX), used in the treatment of cancerous patients, causes toxicity in the different organs of the body. This study of rosmarinic acid (RA) is as an antioxidant on nephrotoxicity and hepatotoxicity induced by MTX., Methods: Rats (n = 32) were divided into four groups: sham; MTX; 100 mg\kg RA + MTX; 200 mg/kg RA + MTX. The amount of MTX was 20 mg/kg. 24 hours after injection of the last dose of MTX, the blood samples and kidneys and liver of rats were studied. The aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, serum creatinine were assessed. Tissue antioxidant enzymes and malondialdehyde (MDA) levels were measured. The liver and kidney tissues were histopathologically examined., Results: MTX significantly increased the urea, creatinine, ALT, AST, ALP levels, and renal MDA and significantly decreased renal catalase (CAT), hepatic glutathione (GSH), and hepatic CAT activity. MTX induced necrosis, leukocyte infiltration, eosinophilic casts, glomerular damage in kidney tissue and necrosis, degeneration and cellular vacuolization in liver tissues. RA at 100 mg/kg caused a significant decrease in ALT and AST and at two doses significantly decreased urea, renal MDA, and liver MDA. RA at 200 mg/kg significantly increased the renal CAT and liver GSH. RA in two doses significantly decreased necrosis and Leukocyte infiltration. RA caused a significant decrease in degeneration and cellular vacuolization in liver tissues., Conclusions: RA with its antioxidant and anti-inflammatory characteristics decreased the MTX induced nephrotoxicity and hepatotoxicity., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Nephrology.)

Carbamazepine, an anticonvulsant drug, has shown antidepressant effects in clinical and experimental models. Nitric oxide (NO) is a neurotransmitter in the central nervous system and has been involved in a variety of diseases including depression. In the present study, the involvement of NO/cyclic GMP/KATP channels pathway in the antidepressant action of carbamazepine was investigated in mice. The antidepressant-like activity was assessed in the forced swim test (FST) behavioral paradigm. Carbamazepine reduced (40 mg/kg, intraperitoneal) immobility period. The antidepressant-like effect of carbamazepine (40 mg/kg, intraperitoneal) was prevented by pretreatment with L-arginine [substrate for NO synthase (NOS), 750 mg/kg, intraperitoneal], sildenafil (a PDE-5 inhibitor, 5 mg/kg, intraperitoneal) and diazoxide (K+ channels opener, 10 mg/kg). Pretreatment of mice with L-NAME (a non-selective NOS inhibitor, 10 mg/kg, intraperitoneal), methylene blue (direct inhibitor of both NOS and soluble guanylate cyclase, 10 mg/kg, intraperitoneal) and glibenclamide (an ATP-sensitive K+ channel blocker, 1 mg/kg, intraperitoneal) produced potentiation of the action of a sub-effective dose of carbamazepine (30 mg/kg, intraperitoneal). Also, carbamazepine (30 mg/kg) potentiated the antidepressant-like effect of fluoxetine through NO modulation. The various modulators used in the study did not produce any changes in locomotor activity per se. The results demonstrated that the antidepressant-like effect of carbamazepine in the FST involved an interaction with the NO/cGMP/KATP channels pathway., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, have been shown to be effective in reducing depression in animal models. The present study aimed to investigate the potential antidepressant-like activity of simvastatin and the possible involvement of opioid systems in the mouse forced swimming test (FST). After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of depressive behavior in mice. Simvastatin (20, 30, and 40 mg/kg, i.p.) or morphine (0.01, 0.1, 1 and 10 mg/kg, i.p.) were administrated 30 min before the OFT or FST. Results showed that simvastatin produced antidepressant effect in a dose-dependent manner. The effect of simvastatin (30 mg/kg) was prevented by the pre-treatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). In addition, a sub-effective dose of simvastatin (20 mg/kg) produced a synergistic antidepressant-like effect in the FST with a sub-effective dose of morphine (0.1 mg/kg) that it was reversed by naloxone. Moreover, in contrast to morphine, treatment with simvastatin for six days induced neither tolerance to the antidepressant-like effect nor withdrawal signs. In conclusion, these findings demonstrated that simvastatin elicited antidepressant-like action possibly through the stimulation of opioidergic pathways, without inducing tolerance and withdrawal signs., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Simvastatin, one of the lipophilic statins, has been shown to be effective in reducing depression in rodents. The present study aimed to investigate the potential antidepressant-like activity of simvastatin and the possible involvement of NO-cGMP-K ATP channels pathway and PPARγ using forced swimming test (FST) in mice. In addition, the interaction between simvastatin and fluoxetine as a reference drug was examined. After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of depressive behavior in mice. Simvastatin at doses (20, 30, and 40 mg/kg, i.p.) was administrated 30 min before the OFT or FST. To evaluate the involvement of NO-cGMP-K ATP channels pathway, mice were pre-treated intraperitoneally with l-arginine (a nitric oxide precursor, 750 mg/kg), L-NAME (a NOS inhibitor, 10 mg/kg), methylene blue (guanylyl cyclase inhibitor, 20 mg/kg), sildenafil (a PDE-5 inhibitor, 5 mg/kg), glibenclamide (ATP-sensitive K + channel blocker, 1 mg/kg), and diazoxide (K + channels opener, 10 mg/kg). Moreover, to clarify the probable involvement of PPARγ receptors, pioglitazone, a PPARγ agonist (5 mg/kg, i.p.), and GW9662, a PPARγ antagonist (2 mg/kg, i.p.), were pre-treated with simvastatin. Immobility time was significantly decreased after simvastatin injection. Administration of L-NAME, methylene blue, glibenclamide and pioglitazone in combination with the sub-effective dose of simvastatin (20 mg/kg, i.p.) reduced the immobility time in the FST compared to drugs alone, while co-administration of effective doses of simvastatin (30 mg/kg, i.p.) with l-arginine, sildenafil, diazoxide, and GW9662 prevented the antidepressant-like effect of simvastatin. In addition, simvastatin (20 mg/kg) potentiated the antidepressant-like effect of fluoxetine through the NO pathway. None of the drugs produced any significant alterations in locomotor activity using OFT. These results demonstrated that NO-cGMP-K ATP channels pathway and PPARγ receptors may be involved in the antidepressant-like effect of simvastatin., (Copyright © 2019 Elsevier Inc. All rights reserved.)