Montelukast Protects Against Renal Damage Due to Cadmium Toxicity: In vivo and In vitro Experiments

Abstract

Background: The protective effects of Montelukast (Mont), as an anti-inflammatory drug, against cadmium-induced kidney cell damage have already been studied and identified. Since the significant part of cadmium nephrotoxicity is caused by oxidative stress, this in vivo and in vitro study was conducted to investigate the possible role of Montelukast antioxidant properties in the protection. Methods: In the in vivo section, 42 rats were treated in seven groups of six rats as follows: Control; Cadmium Chloride (CdCl2) control; Montelukast control; CdCl2 plus Montelukast treatment; CdCl2 with Montelukast pre-treatment; Vitamin E control; CdCl2 plus Vitamin E treatment. In the in vitro section, human embryonic kidney cells (HEK293) were treated with CdCl2; Montelukast; Combined CdCl2 and Montelukast; Vitamin E; Combined CdCl2 and Vitamin E. Results: Montelukast, in both treatment and pretreatment forms, reduced serum urea, creatinine, and potassium levels compared to CdCl2 group, in vivo. Similar to vitamin E, the pre-treatment with Montelukast was associated with a significant decrease in Nitric Oxide (NO) and Total Antioxidant Capacity (TAC) in serum and renal tissue, and a significant increase in Glutathione Peroxidase (GPX) activity in serum compared those in the CdCl2 group. In the in vitro section of the study, Montelukast significantly reduced Malondialdehyde (MDA) and NO while the TAC level, Superoxide Dismutase (SOD), and the GPX activity increased significantly. Conclusion: Overall, the antioxidant effects of Montelukast appear to play a prominent role in preventing the renal toxicity due to cadmium exposure.

The renoprotective potential of montelukast: a scoping review

“…We also examined several RCTs about the effect of montelukast in nephrotoxicity or acute kidney damages in rats induced by lipopolysaccharide (LPS) 24 , diclofenac 30 , amikacin 31 , Escherichia coli 41 , cyclosporine 28 , MTX 29 , cobalt-60 gamma radiation sources 42 , doxorubin 25 , and cadmium 43 , and all studies resulted in montelukast having therapeutic effects by its anti-inflammatory, anti-apoptic, and antioxidant effects. It has been shown in multiple studies that montelukast also has an effect on inhibiting neutrophil infiltration.…”