Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis and protect the liver until now. We intended to discover the empagliflozin’s (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity and reducing HIF-1α. Rats were treated orally with EMPA (3 or 6 mg/kg) with TAA (100 mg/kg, IP) thrice weekly for 6 weeks. EMPA in both doses retracted the serum GGT, ALT, AST, ammonia, triglycerides, total cholesterol, and increased serum albumin. At the same time, EMPA (3 or 6 mg/kg) replenished the hepatic content of GSH, ATP, AMP, AMPK, or SIRT-1 and mitigated the hepatic content of MDA, TNF-α, IL-6, NF-κB, or HIF-1α in a dose-dependent manner. Likewise, hepatic photomicrograph stained with hematoxylin and eosin or Masson trichrome stain of EMPA (3 or 6 mg/kg) revealed marked regression of the hepatotoxic effect of TAA with minimal injury. Similarly, in rats given EMPA (3 or 6 mg/kg), the immunohistochemically of hepatic photomicrograph revealed minimal stain of either α-SMA or caspase-3 compared to the TAA group. Therefore, we concluded that EMPA possessed an antifibrotic effect by targeting AMPK/SIRT-1 activity and inhibiting HIF-1α. The present study provided new insight into a novel treatment of liver fibrosis.

ZnO/KCl nanocomposite was prepared by solgel to appreciate the role of synthesized ZnO-NPs to curb obesity in a high-fat diet rat model. KCl played an important role in decreasing the particle size (30 nm) and also in facilitating the suspension formation of ZnO-NPs. XRD and HRTEM were carried out to estimate the particle size while SEM was used to investigate the morphology of the nanoparticles. XPS measurements were used to examine the chemical compositions of the nanocomposite. XRD declared that ZnO has a hexagonal wurtzite structure. The Rietveld refinement has also been executed (chi 2 = 1.0 and R-factor was 0.05). The treatment of obese rats with ZnO-NPs enhanced the adiponectin level, hepatic carnitine (Car) and reduced hepatic glutathione (GSH) with lowering the liver enzymes and pathological changes. The treatment coused a decrease in body weight gain, Body mass index (BMI), leptin level, cholesterol, triglycerides, glucose, immunohistochemistry for nuclear factor kappa (NFκB), the insulin resistance index (HOMA-IR) and a reduction in hepatic malondialdehyde (MDA), nitric oxide (NO), and 8-Hydroxy-2'-deoxyguanosine (8OHdG). The results indicated a positive correlation between BMI and oxidative stress parameters. In conclusion, ZnO-NPs manifested valuable anti-obesity effects via lowering body weight gain, oxidative stress, BMI, lipids, and insulin resistance.