Probing the Nephroprotective Potential of Chrysin against Methotrexate-Induced Tubulointerstitial Nephritis and Oxidative Damage

Abstract

In a bid to treat cancer, there may be a possibility of adverse consequences for tissues such as the kidneys. Methotrexate is an effective drug of choice used in high dosages as a first-line treatment in the management of cancer. Nevertheless, it can induce tubulointerstitial nephritis (TIN), which may finally result in renal failure. Therefore, there is need to identify substances that can alleviate and protect the kidneys from such TIN, and, by extension, provide a safe environment to be co-administered with methotrexate. The study aimed to probe the nephroprotective efficacy of chrysin on the kidneys against methotrexate-induced TIN. A total of 25 adult female Wistar rats with an average weight of 200 g were randomly segregated into five (A-E, n = 5). Group A was allowed feed and water only, serving as the normal control. Group B received 20 mg/kg bw of methotrexate only. Group C received chrysin (100 mg/kg bw). In groups D and E, methotrexate administration was followed by chrysin treatment in low (50 mg/kg bw) and high (100 mg/kg bw) dosages, respectively. The results obtained from the study demonstrated significant attenuation of serum urea, creatinine, and electrolyte disturbances, attenuation of oxidative stress (superoxide dismutase, glutathione peroxidase, and catalase), and lipid peroxidation via malondialdehyde optimization while preserving the histoarchitecture of the kidneys of rats treated with chrysin in high dosage. The extrapolation from this study proposes the nephroprotective effect of high-dose chrysin against methotrexate-induced tubulointerstitial nephritis by suppressing oxidative stress and inflammation in the renal parenchyma.