montelukast and Acute-Kidney-Injury

Renal toxicity is one of the most severe complications that can occur with cisplatin (CIS) administration in cancer patients. Montelukast (ML) renoprotective outcome contrary to CIS-drawn nephrotoxicity remains obscure. Therefore, adult male Sprague-Dawley rats were orally given ML (10 and 20 mg/kg/day) 5 days before and after single CIS (5 mg/kg; i.p.) treatment. ML returned blood urea nitrogen, as well as serum creatinine and gamma glutamyl transferase that were elevated by CIS to normal level. The improved kidney function tests corroborated the attenuation of CIS renal injury at the microscopical level. It also reduced serum/renal nitric oxide and renal hemeoxygenase-1. Meanwhile, ML hindered the raised levels of serum endothelin-1, serum and renal tumor necrosis factor-α, and monocyte chemoattractant protein-1. These effects were associated by deceased caspase-3 expression in kidney after ML treatment. In conclusion, ML guards against CIS-induced nephrotoxicity via anti-inflammatory and antiapoptotic properties.

Topics: Acetates; Acute Kidney Injury; Animals; Caspase 3; Cisplatin; Cyclopropanes; Drug Evaluation, Preclinical; Kidney; Leukotriene Antagonists; Male; Quinolines; Rats, Sprague-Dawley; Sulfides

Nephrotoxicity is a major complication of gentamicin (GEN). We aimed to evaluate the potential protective effect of montelukast (MK) against GEN-induced nephrotoxicity in rats. Thirty-two rats were randomly divided into four groups, each consisting of eight animals as follows: (1) the rats were control; (2) intraperitoneally injected with GEN 14 consecutive days (100 mg/kg/day); (3) treated with GEN plus distilled water via nasogastric gavage for 14 days; and (4) treated with GEN plus MK (10 mg/kg/day) for 14 days. After 15 days, rats were killed and their kidneys were taken and blood analysis was performed. Twenty-four hours urine collections were obtained in standard metabolic cages a day before the rats were killed. Tubular necrosis and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in the other part of kidneys. Statistical analyses were made by the chi-square test and analysis of variance. Serum urea and creatinine levels were significantly higher in rats treated with GEN alone, than the rats in control and GEN + MK groups.The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of MK to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and MK had significantly lower MDA and NO levels in kidney cortex tissue than those that was given GEN alone. In rats treated with GEN + MK, despite the presence of mild tubular degeneration and tubular necrosis are less severe, and glomeruli maintained a better morphology when compared with GEN group. We can say that MK prevents kidney damage with antioxidant effect, independently of NO.

Topics: Acetates; Acute Kidney Injury; Animals; Anti-Bacterial Agents; Cyclopropanes; Drug Evaluation, Preclinical; Gentamicins; Kidney; Leukotriene Antagonists; Male; Quinolines; Rats; Rats, Wistar; Receptors, Leukotriene; Sulfides; Urine

In this study, the therapeutic and protective effects of montelukast against cisplatin (CP)-induced acute renal damage were investigated.. Thirty-five female rats were divided into five groups as follows: (1) control, (2) montelukast (10 mg/kg daily for 10 days per-oral (p.o.), (3) CP (single dose 7 mg/kg intraperitoneally (i.p.)), (4) CP + montelukast (10 mg/kg daily for 10 days p.o., after 3 days of the injection of CP), (5) montelukast (10 mg/kg daily for 10 days p.o.) + CP (single dose 7 mg/kg i.p., after the last dose of montelukast). At the end of the experiment, malondialdehyde (MDA), a lipid peroxidation product, myeloperoxidase (MPO), and reduced glutathione (GSH) levels were determined in the renal tissue. Also, blood urea nitrogen (BUN) and creatinine (Cr) levels were assayed from the trunk blood samples.. CP treatment caused a significant elevation of MDA, MPO, BUN, and Cr levels when compared with the control group. Also, GSH levels were found to be reduced due to the CP treatment. Montelukast administration after CP injection ameliorated all of these parameters. Our histopathological findings (marked swelling of epithelial cells, tubular dilatation, tubular desquamation, and loss of brush border in the kidney) were consistent with the biochemical results.. Montelukast treatment after CP injection exerted therapeutic effects against CP-induced acute kidney damage.

Topics: Acetates; Acute Kidney Injury; Animals; Blood Urea Nitrogen; Cisplatin; Creatinine; Cyclopropanes; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Glutathione; Injections, Intraperitoneal; Kidney; Leukotriene Antagonists; Malondialdehyde; Oxidative Stress; Peroxidase; Quinolines; Rats; Rats, Wistar; Spectrophotometry; Sulfides; Treatment Outcome