Beta-caryophyllene ameliorates environmental toxicants-induced experimental nephrotoxicity through regulation of redox system and inflammation

Abstract

Kidneys play important roles in the detoxification and excretion of toxic metabolites making them vulnerable to xenobiotic toxicity. We investigated the possible nephrotoxicity induced in mice by environmental toxicants diethyl nitrosamine (DEN) and carbon tetrachloride (CCl4) and their mitigation by supplementation of natural bicyclic sesquiterpene β-caryophyllene (BCP). DEN (1 mg/kg) and CCl4 (0.2 mL/kg) were given to mice and then the treatment group received BCP (30 mg/kg). After 18 weeks, DEN/CCl4-induced mice showed renal injury evidenced by significant increase in circulating kidney function markers as well as histopathological alterations. Concurrent supplementation of BCP significantly ameliorated kidney function markers and prevented renal tissue damage. BCP treatment suppressed lipid peroxidation and nitric oxide levels and enhanced the antioxidant defence mechanism in the kidneys. BCP successfully amended renal histopathological changes and improved kidney serum markers and electrolytes associated with kidney function in association with alleviation of the deteriorated renal oxidative state and antioxidant defence system. BCP modulated the expression of key inflammation markers (inducible nitric oxide synthase and cyclooxygenase-2) and apoptotic markers [caspase-3 and poly (ADP-ribose) polymerase] in the DEN/CCl4-exposed kidneys. The study concludes that exposure to environmental toxicants DEN/CCl4 caused extensive nephrotoxicity that was notably mitigated by BCP suggesting its effectiveness as an alternative therapy in renal dysfunctions.