Montelukast attenuates side effects of cisplatin including testicular, spermatological, and hormonal damage in male rats

Abstract

In the current study, the protective effect of montelukast (ML) on cisplatin induced reproductive toxicity in rats was investigated. Twenty-eight rats were equally divided into four groups; first group was kept as control. In the second group, ML was orally administered at the dose of 10 mg/kg/day for 10 days. In the third group, CP was intraperitoneally administered at the dose of 7 mg/kg a single injection, and in fourth group, CP and ML were given together at the same doses. Although CP induced oxidative stress via significant increase in the formation of TBARS, it caused a significant decline in the levels of GSH, CAT, GPx, and SOD in rats. In contrast, ML prevents these effects of CP through cause an increase in GSH, CAT, GPx, and SOD levels and a decrease in formation of TBARS. In addition, sperm motility and serum testosterone levels significantly decrease and histopathological damage increases with CP treatment. However, the effects of CP on sperm motility, serum testosterone level, oxidative and histopathological changes are eliminated by ML treatment. In conclusion, the current study demonstrated that the reproductive toxicity caused by CP may be prevented by ML treatment. Thus, it was judged that co-administration of ML with CP may be useful to attenuate the negative effects of CP on male reproductive system.

Beneficial Effects of Montelukast against Cisplatin-Induced Acute Renal Damage in Rats

“…Also more recently, we reported that the reproductive toxicity caused by CP may be prevented by montelukast treatment. 17 All of the investigations mentioned above encouraged us to plan this experimental design for the first time. In this context, in order to determine the beneficial effects of montelukast that is protective or therapeutic against CP toxicity, montelukast must be given both after and before CP injections.…”

“…17,[26][27][28] One of its most frequent and serious side effects is nephrotoxicity, which is described as acute tubular necrosis (ATN). Although the mechanisms of CP-induced nephrotoxicity are not fully understood, one mechanism of this toxicity is believed to involve ROS generation and inflammatory machine in the pathophysiology of CP-induced ATN after even a single dose of the drug.…”

“…Consistent with these important findings, we have previously reported that a selective reversible CysLT1 receptor antagonist, montelukast (MK-0476), has significant antioxidant properties against CP-induced testicular damage. 17 The protective effects of montelukast have also been previously addressed in other models of cell damage induced by several drugs. 18 The beneficial effects of montelukast in various experimental models of inflammation have also been reported.…”

“…plus single-dose CP injection after the last dose of montelukast (montelukast + CP). The applied montelukast duration (10 days) was chosen on the basis of previous montelukast-related studies 17,22 to compare both the obtained findings. Behind the therapeutic effect of montelukast, the aim of this study was to investigate the possible protective effects of montelukast; therefore, montelukast was administered before CP treatment.…”

The beneficial effects of Montelukast against 2,3,7,8-tetrachlorodibenzo- p -dioxin toxicity in female reproductive system in rats

“…Several studies also showed that ML has a significant antioxidative effect on inhibition of lipid peroxidation in some tissues such as testis and liver 9,10 . Cuciureanu et al 11 demonstrated a partial hepatoprotective effect of montelukast against carbon tetrachloride induced hepatopathy on rats.…”