THE AMELIORATING EFFECTS OF BILBERRY ON METHOTREXATE-INDUCED INTESTINAL INJURY

Abstract

Objective: Methotrexate (MTX) is a folic acid analogue chemotherapeutic used in the treatment of some malignant tumors and autoimmune diseases. In addition to its antitumoral properties, it can also exhibit toxic effects on the kidney and intestines. Bilberry (BB) fruit is a potent natural antioxidant rich in anthocyanidins. The purpose of this study was to investigate the potential ameliorating effects of BB against MTX-induced intestinal damage using biochemical and histological methods. Material and Methods: Twenty-one adult female Sprague Dawley rats were divided into three equal groups. No procedure was performed on the control group (ControlG), while the MTX group (MTXG) and MTX+BB extract group (MTX+BBG) received a single intraperitoneal dose of 30 mg/kg MTX on the first day of the experiment. MTX+BBG also received 200 mg/kg BB extract by oral gavage once daily for five days starting on the first day of the experiment. Half the intestinal tissues removed from the duodenal region at the experiment were used for biochemical evaluation, and the other half for histological examination. Results: Malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), and 8-oxo-2′-deoxyguanosine (8- OHdG) values were all higher in MTXG intestinal tissues than in ControlG. MDA, TOS, OSI, and 8-OHdG values were lower in MTX+BBG than in MTXG. In addition, caspase-3 levels in MTXG were higher than those in both ControlG and MTX+BBG, while total antioxidant status (TAS) values were lower. In terms of histology, villous hemorrhage, inflammatory cell infiltration, fusion, and degeneration in the villus epithelium were present in MTXG intestinal tissue, and the total damage score was also high. Improvement in all these parameters was present in MTX+BBG. Conclusion: Orally administered BB extract can improve MTX-induced intestinal damage through its antioxidant and anti-inflammatory effects.