Xanthine oxidase inhibition by medicinal plants mitigates tenofovir-induced nephrotoxicity: a comprehensive...

Tenofovir, a nucleotide reverse transcriptase inhibitor (NRTI), is a first-line therapy for HBV and HIV and is administered as tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF). However, long-term use of TDF is linked to renal and other organ toxicities, which is largely attributed to oxidative stress mediated by xanthine oxidase (XO), a key enzyme in purine metabolism. To address this, plants with documented nephroprotective and XO-inhibitory properties were investigated through computational, in vitro, and in vivo approaches.

Bioactive compounds from nine medicinal plants were subjected to computational screening for XO inhibition, leading to the selection of Allium cepa and Vitex negundo as promising candidates. Fifteen extracts from different plant parts were prepared and assessed in vitro for XO inhibitory activity. The methanolic extract of A. cepa bulb (AC) and the hydroalcoholic extract of V. negundo root (VN) demonstrated the highest potency. These extracts were further evaluated for their antioxidant potential and tested against TDF-induced renal and hepatic toxicities in a 35-day rat model.

Both AC and VN significantly mitigated TDF-induced elevations in serum biomarker levels, including creatinine, BUN, AST, ALT, GGT, bilirubin, and alkaline phosphatase, while enhancing albumin levels. They also restored the levels of oxidative stress markers such as MDA, GSH, catalase, and SOD. Histopathological examination confirmed substantial structural recovery of liver and kidney tissues.

Overall, this preclinical study demonstrates that A. cepa and V. negundo extracts effectively alleviate TDF-induced organ toxicities and oxidative damage, supporting their potential as adjunct therapies to enhance the safety of TDF treatment in HBV and HIV management.