Evaluation by different mechanisms of the protective effects of vitamin B12 on methotrexate nephrotoxicity

Ozturk E., KARABULUT D., AKİN A. T., KAYMAK E., Kuloglu N., YAKAN B.

JOURNAL OF MOLECULAR HISTOLOGY, vol.53, no.1, pp.133-143, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 53 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1007/s10735-021-10027-9
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.133-143
  • Keywords: Biochemistry, Histopathology, Immunohistochemia, MTX, Rat, RHEUMATOID-ARTHRITIS, EXPRESSION, APOPTOSIS, INJURY, RATS
  • Erciyes University Affiliated: Yes


Methotrexate is used for cure of many cancer types. It has many side effects. For this reason, obtaining a nephroprotective agent is obligatory. In the study, our aim is to determine probable effects of Vitamin B12 on MTX caused kidney damages in rats. Rats were randomly divided into 4 groups, including 8 animals in each group. Control group, VitB12 group (3 mu g-kg-ip B12 throughout 15 days), MTX group (at the 8th day of experiment, a single dose of 20 mg-kg-ip MTX), Vit B12 + MTX group (3 mu g-kg-ip B12 throughout 15 days and at the 8th day of experiment, a single dose of 20 mg-kg-ip MTX) Animals were anesthetized and kidney tissues were removed to evaluate biochemically, immunohistochemically and histopathologycally. There were histopathological deteriorations, rises of apoptotic cells, expressions of heat shock proteins, endoplasmic reticulum stress and inflammation markers in the MTX group. In the MTX group, Superoxide Dismutase (SOD), Total Antioxidant Status (TAS) and Catalase (CAT) levels decreased, but Total Oxidant Status TOS, Malondialdehyde (MDA) and interleukin-6 (IL6) levels increased. In addition, there was amelioration in kidney tissue in Vit B12 + MTX group compared to the MTX group. We suggest that Vit B12 can be used to reduce the toxic effects of MTX.