Investigation of the effect of cannabidiol on kidney damage caused by cisplatin use

Cisplatin (CIS) is a widely used chemotherapeutic agent in cancer treatment, but it causes severe nephrotoxicity, leading to significant kidney dysfunction. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, possesses tissue-protective properties by anti-inflammatory, antioxidant, and anti-apoptotic effects. This study aimed to elucidate the molecular protective effects of CBD in nephrotoxicity induced by high-dose CIS administration. In the study, 32 male Wistar Albino rats were randomly divided into 4 groups (n=8): Control, CIS (7.5 mg/kg, single intraperitoneal dose), CBD (5 mg/kg/day, intraperitoneal for 5 days), and CIS+CBD. On the 5th day, rats were sacrificed following abdominal incision, surgical exanguination was performed. Histopathological, immunohistochemical [tumor necrosis factor-alpha (TNF-alpha), caspase-3 (Cas-3), inducible nitric oxide synthase (iNOS)], biochemical [total oxidant status, total antioxidant status, oxidative stress index (OSI), urea, creatinine], and genetic [Sirtuin 1 (SIRT1), p53, Bcl2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2), Kelch-like ECH-associated protein 1 (Keap-1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1)] analyses were performed on the kidney tissues. In the CIS group, histopathological findings showed increased immunoexpression of TNF-alpha, Cas-3, and iNOS, as well as elevated OSI, urea, creatinine levels biochemically, and p53 and Bax mRNA expression genetically. Conversely, there was a decrease in SIRT1, Bcl2, Keap-1, Nrf2, and HO-1 mRNA expression. Treatment with CBD reversed all of these findings. Based on these results, CBD exhibited both direct and indirect anti-inflammatory, antioxidant, and anti-apoptotic effects through various mechanisms. These findings suggest that CBD could reduce CIS-induced nephrotoxicity and may be considered as a potential adjunct in chemotherapy regimens for cancer patients.