Investigation of the protectie effect of black mulberry (morus nigra L.) extract on cisplatin-induced nephrotoxicity in rats

Cisplatin is an antineoplastic / cytotoxic agent used in cancer treatment and may cause various side effects such as nephrotoxicity, hepatotoxicity, mucositis, abnormal changes in blood parameters and peripheral neuropathy. It is reported that these side effects appear due to the deterioration of the oxidant-antioxidant balance in the oxidant direction. The studing aiming to bring this axidant/antioxidant disequbilium in to ladance might impose cisplatin based cancer chemotherapy therefore, it the aim of this study is to investigate the protective effects of the extract obtained from Black Mulberry (Morus nigra) extracts, which has rich polyphenolic content, high antioxidant and anti-inflammatory activity, on cisplatin-induced rat model of nephrotixicity. Ethanol, methanol and aqueous extracts were prepared from black mulberry samples and their Iron (III) Ion Reducing Antioxidant Capacity (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), total antioxidant capacity (TAS), total phenolic content and 2.2''-azino-bis (3 ethylbenzothiazoline-6-sulfonic acid (ABTS) antioxidant activity anaysis were perform the most appropriate activity has shown on the methonolic extract group which was used in the next part of the study. In animal experiments, 5 different groups (control group, black mulberry group [KD], cisplatin group, Cis + 200 mg / kg KD group and Cis + 400 mg / kg) consisting of Wistar Albino female rats, each 3-4 months old (n = 7) KD group) left. Saline was administered to the control group for 12 days, black mulberry methanolic extract for 12 days (400 mg / kg / day) to the black mulberry group; Cisplatin (7.5 mg / kg) on the 5th day in the Cisplatin group, 7.5 mg / kg cisplatin on the 5th day and black mulberry methanol extract for 12 days (200 mg / kg / day and 400 mg) in the treatment groups. / kg / day) given orally. On the 12th day, all rats were sacrificed after blood was taken from all groups by intracardial route under anesthesia. In the blood; Blood urea nitrogen (BUN), creatinine (CREA), total antioxidant capacity - total oxidant capacity (TAS-TOS) were measured and oxidative stress index (OSI) levels were calculated. Superoxide Dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), Caspase-3 (Caspase-3), TAS, TOS levels were measured in the kidney tissue and the OSI index was calculated. In addition, histopathological evaluation of the kidney tissue was made. Methanolic extract was found to have the highest antioxidant activity among the black mulberry extracts and this extract was given to rats. After acute kidney injury induced by cisplatin in rats, BUN, creatine and TOS levels of the treatment groups were significantly decreased (p<0.05), while the TAS level was significantly increased compared to the cisplatin group. Significant decrease in MDA, caspase-3 and TNF-α levels in kidney tissue samples (p<0.05), and a significant increase in TAS, SOD and CAT levels compared to cisplatin group (p<0.05). Histopathological evaluation showed anatomic and physiologic significant impairments in the cisplatin group compared to the control group. Also Proximal and distal epithelial cell loss and debris accumulation were found to be decreased in the high and low dose black mulberry groups compared to the cisplatin group (p<0.05). In terms of biochemical and histological results, it was determined that high dose black mulberry was more effective against nephrotoxicity than low dose. As a result, it has been observed that black mulberry has a protective effect against cisplatin-induced kidney damage and oxidative stress.