Ketotifen attenuates paraquat-induced nephrotoxicity in mice via suppression of oxidative stress and inflammation

Abstract

Paraquat (PQ) is a toxic herbicide to humans and animals that causes kidney damage. Ketotifen (KTF) is a first-generation antihistamine and a potent mast cell stabilizer with antioxidant and anti-inflammatory properties. This study aimed to evaluate the protective effect of KTF against PQ-induced nephrotoxicity in mice by suppressing inflammation, oxidative stress, and inducible nitric oxide synthase (iNOS). Thirty-five male NMRI mice were randomly divided into 5 groups (n = 7) as follows: control group receiving normal saline as vehicle (10 mL/kg/day, IP), KTF, PQ, PQ + KTF 2, and PQ + KTF 4 groups. PQ was administered as a single dose (30 mg/kg, IP) on day 4. The mice received KTF at the doses of 2 and 4 mg/kg/day, IP, for seven days. On the eighth day of the study, the mice were anesthetized, and their kidneys were removed. Then, oxidative stress and inflammation factors and iNOS protein expression were evaluated, and histological examinations were performed. KTF resulted in a significant decrease in blood urea nitrogen, creatinine, thiobarbituric acid-reactive substances, tumor necrosis factor alpha, and iNOS protein expression, and a significant increase in albumin, total thiol, and the activity of antioxidant enzymes including catalase, superoxide dismutase, and glutathione peroxidase in PQ-induced nephrotoxicity compared with the PQ group, which were confirmed by histopathological findings. The results of this study showed that KTF could improve PQ-induced renal injury in mice by reducing oxidative stress, inflammation, and iNOS protein expression.