Hesperidin mitigates Doxorubicin-induced hepatic toxicity in rats, targeting JAK-STAT signaling pathway

Abstract

Even though doxorubicin (DOX) is an excellent cancer chemotherapy, its adverse impacts, including hepatotoxicity, restrict its clinical usefulness. The study's goal was to assess hesperidin's (HSP) hepatoprotective impact in rats exposed to DOX as well as any potential underlying mechanisms. Thirty male albino rats were split into three: DOX, DOX+HSP, and control (10/group). Serum liver enzymes, triglycerides (TG) and cholesterol, hepatic MDA, superoxide dismutase (SOD), serum TNF-α, IL-6, IL-10, liver-expressed JAK2, STAT3 genes, and organ index were assessed. There were additional evaluations of NF-kB and caspase-3 immunoreactions in the liver. The results revealed that hepatic SOD, IL-10, and liver index values all substantially declined in response to DOX-induced damage. But compared to the control group, there was a dramatic rise in the JAK2 and STAT3 genes, as well as hepatic MDA, TNF-α, and IL-6. There was also an increase in blood liver enzymes, serum cholesterol, and TG. In the liver, caspase-3 and NF-kB immunoreactions were also up-regulated. HSP dramatically improved DOX-induced changes in the liver. It can be concluded that, in addition to down-regulating the JAK2/STAT3 signaling cascade, HSP also employed antioxidant, anti-inflammatory, and anti-apoptotic mechanisms to mitigate the hepatotoxicity induced by DOX.