Alpha-lipoic acid prevents doxorubicin-induced acute hepatorenal toxicity in rats by reducing oxidative and inflammatory stress to suppress autophagy

Doxorubicin (DOX) is a commonly used medicine in cancer therapy. This drug accumulation in healthy tissues causes harmful clinical outcomes. Strategies that reduce oxidative damage, including alpha-lipoic acid (ALA) treatment, have been proposed to diminish toxic effects on healthy cells by raising the therapeutical effect of DOX on cancer cells. In this study, the preventive effects of ALA, against DOX-induced hepatorenal harm in rats were researched biochemically, molecularly, histopathological, and immunohistochemical. The experiment was designed for 10 days and 4 groups of 8 rats were created. ALA was administered orally to rats at a dosage of 200 mg/kg for 10 days and DOX was administered intraperitoneally at an only dosage of 30 mg/kg on day 8. To define oxidative stress, SOD, GSH, MPO, MDA, GPx, and CAT levels were evaluated. Hepatorenal harm was detected both histopathologically and by serum creatinine, ALT, ALP, AST, and urea analyses To detect the effect of inflammation, NF-κB, IL-1β, TNF-α levels, were defined in the liver, and AQP-2 and NPHS1 levels in the kidney. In addition, APG5L, Beclin 1, and LC3B expressions were determined immunohistochemically. It was determined that DOX-induced oxidative harm reduced and hepatorenal function markers improved in ALA-applied groups. It was also determined that ALA pretreatment had a regulative effect on NF-κB, AQP-2, TNF-α, NPHS1, and IL-1β levels and prevented the rise in DOX-induced LC3B, Beclin 1, and APG5L expression. Histopathological analysis showed that it prevented hepatorenal harm. As a result, ALA demonstrated its protective potential against DOX-induced hepatorenal toxicity.