Possible protective effects of two different doses of cyanocobalamin against methotrexate nephrotoxicity in rats

Authors

  • Noor Mohammed Alduboni Pharmacy Section, Alkarkh Health Directorate Baghdad, MOH, Baghdad, Iraq
  • Nada N Al-Shawi

DOI:

https://doi.org/10.31351/vol31iss2pp212-217

Abstract

Abstract

   Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rats through the involvement of Nrf2/keap1 molecular mechanism in this respect. Rats utilized in this study were randomized into 4 groups (ten rats per each group); Group 1- (Control) rats intraperitoneally injected with 0.5ml normal saline once daily for 7 consecutive days. Group 2- Rats intraperitoneally injected with 0.5ml normal saline once daily for 7 consecutive days; and at day 2, a single intraperitoneal dose of methotrexate (20mg/kg) is to be injected. Group 3- Rats intraperitoneally injected with a 0.5mg/kg cyanocobalamin once daily for 7 consecutive days, and at day 2, a single intraperitoneal dose of methotrexate (20mg/kg). Group 4- Rats intraperitoneally injected with a 2mg/kg cyanocobalamin once daily for 7 consecutive days, and at day 2, a single intraperitoneal dose of methotrexate (20mg/kg). Co-administration of cyanocobalamin at doses cyanocobalamin 0.5mg/kg and 2mg/kg with methotrexate showed significant  reduction  (P<0.05) in malondialdehyde, significant elevation (P<0.05)  in reduced glutathione level, significant upregulation in  renal Nrf2 expression and significant down regulation in renal keap1 expression each compared to corresponding levels in methotrexate-only treated group. In conclusion this study demonstrated that co-administration of cyanocobalamin at two different doses with MTX resulted in attenuation of its nephrotoxicity by the utilization of selected parameters.

Keywords: Nephrotoxicity, methotrexate, cyanocobalamin, malondialdehyde, glutathione, Nrf2, Keap1.

How to Cite

1.
Alduboni NM, N Al-Shawi N. Possible protective effects of two different doses of cyanocobalamin against methotrexate nephrotoxicity in rats. Iraqi Journal of Pharmaceutical Sciences [Internet]. 2022 Dec. 24 [cited 2024 Dec. 29];31(2):212-7. Available from: https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/1632

Publication Dates

References

Gabriel, T. Montezuma, S. Renato D. Foresto. Drug-Induced nephrotoxicity. Rev. Assoc. Med. Bras. 2020; 66(1):s82-s90. doi: 10.1590/1806-9282.66.S1.82.

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Published

2022-12-24