Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 169, Issue -, Pages 99-109Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2021.03.035
Keywords
Methotrexate; Dioscin; Hepatotoxicity and nephrotoxicity; miR-145-5p; Sirt5; Oxidative stress
Funding
- LiaoNing Revitalization Talents Program [XLYC1802121]
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Dioscin can alleviate MTX-induced hepatorenal damages by regulating oxidative stress mediated by miR-145-5p. This natural product may be considered as an effective drug for treating this disorder in the future.
Dioscin, one natural product, has various pharmacological actions. However, its effects on methotrexate (MTX)induced hepatorenal damages still remain unknown. In the present study, the data manifested that dioscin restored the viabilities of L-02 and NRK-52E cells, reduced ALT, AST, Cr, BUN levels, and ameliorated histopathological changes of liver and kidney. Besides, dioscin decreased ROS levels in cells, and adjusted SOD, MDA, GSH and GSH-Px levels in rats. Dioscin reduced the expression levels of miR-145-5p which directly targeted Sirt5, and then regulated the expression levels of SOD1, Nrf2, Gst, Keap1, HO-1, GCLC and NQO1. MiR-145-5p mimic in cells deteriorated ROS levels and decreased Sirt5 expression to accentuate oxidative stress by regulating the expression levels of SOD1, Nrf2, Keap1, which were all reversed by dioscin. Moreover, MTX-induced hepatorenal damage were worsened in mice by Sirt5 siRNA or miR-145-5p agomir, which were also alleviated by dioscin. Dioscin relieved MTX-induced hepatorenal damages through regulating miR-145-5p-medicated oxidative stress, which should be considered as one effective drug to treat the disorder in future.
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