Nano cerium oxide and cerium/zinc nanocomposites characterization and therapeutic role in combating obesity via controlling oxidative stress and insulin resistance in rat model.

BACKGROUND: CeO2NPs and ZnONPs can curb the increase of cholesterol and triglycerides observed in rats with non-alcoholic fatty liver disease. It was suggested that CeO2 NPs could potentially have an insulin-sensitizing effect, specifically on adipose tissue and skeletal muscle. It was reported that ZnONPs combat the increase of insulin resistance observed in obese rats and could be beneficial value in NAFLD. In our previous work, ZnO-NPs manifested valuable anti-obesity effects via lowering body weight gain, oxidative stress, BMI, lipids, and insulin resistance. METHODS: In the present study, cerium oxide nanoparticles (A-1) and cerium/zinc nanocomposites (A-2 and A-3) were synthesized by solgel to investigate their role on oxidative stress, adipocyte hormones, and insulin resistance in an obese rat model. X-ray diffraction, HRTEM, SEM, and XPS were carried out to confirm the crystal structure, the particle size, the morphology of the nanoparticles and the oxidation states. RESULTS: The Rietveld refinement has also been executed on A-1 (chi2 = 1.00; average Bragg = 2.92%; R-factor = 2.45%) and on A-2 (Rw = 9.87%, Rex= 9.68%, χ2 = 1.04, GoF = 1.02). The XPS spectra indicated the presence of Ce in + 4 and + 3 oxidation states and Zn as ZnO and ZnO.OH. Cerium oxide and ZnO crystal sizes lie in the range 40.53-45.01 and 40.53-45.01 nm, respectively. The results indicated that treating obese rats with any of the tested nano compounds (5 mg or 10 mg/Kg) lowered plasma cholesterol, triglycerides, LDL, insulin resistance, glucose, and BMI significantly relative to obese group values. On the other hand, HDL increased significantly in obese rats after treatment with either A-2 or A-3 compared to obese rats. The current investigation showed antioxidant activities for A-1, A-2, and A3 as evidenced by the significant increase in GSH level and a significant decrease in MDA. CONCLUSION: It was found that A-1, A-2, and A-3 have an efficient therapeutic role in treating of obesity-related hyperlipidemia, oxidative stress and insulin resistance. The results of A-2 and A-3 were more pronounced than those of A-1. The use of Zn/Ce nanocomposite (that have positive characteristics) in combating obesity and its complications could be become a new trend in therapeutic application for a management of obesity.

Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis.

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.