Boldine provides protective effect against nephrotoxicity induced by cisplatin in Wistar rats: Role of oxidative stress, inflammation and caspase-3

[摘要] Side effects of cisplatin, especially dose-dependent nephrotoxicity, are major factors limiting its use in cancer.Boldine ((S)-2, 9-dihydroxy-1, 10-dimethoxy-aporphine) is a natural alkaloid known for its strong antioxidant activitypresent in leaves/bark of boldo tree (Peumus boldus Molina), a native tree in Chile. Here, we aimed to investigate thenephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal injury. Thirty Wistaralbino rats divided into 5 groups (Control, Cis, Bold.40, Cis + Bold.20, Cis + Bold.40 groups) were used. Rats receivedboldine (20 or 40 mg/kg/day), or vehicle (saline) intraperitoneal for 14 days and a single dose cisplatin (7 mg/kg, ip)was applied on the 10th day to induce nephrotoxicity. Rats and kidney tissue were weighed to determine kidneyindex. Blood urea nitrojen (BUN) and creatinine levels, the amount of thiobarbituric acid reactive substances (TBARS,an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities andtumor necrosis factor alpha (TNF-α) levels were measured and histopathologic examination was performed. Induciblenitric oxide synthase (iNOS) and caspase-3 expressions were detected immunohistochemically. Nephrotoxicityinduced by cisplatin was apparent by elevated levels of BUN, creatinine, kidney index, TBARS and TNF-α, anddecreased body weight, SOD and GPx enzyme levels. Pretreatment with boldine protected the renal function at bothboldine doses by fixing the renal damage markers, oxidative stress, caspase-3 and iNOS expression. Histopathologicalfindings supported biochemical findings. Taken together these findings indicate that boldine has promising protectiveeffect against cisplatin nephrotoxicity by improving oxidative stress, inflammation, histopathological alterations andby alleviating caspase 3 expression.

[学科分类] 仪器

[关键词] Boldine;Caspase-3;Cisplatin nephrotoxicity;Inflammation;Oxidative stress