Effects of Curcumin on Autophagy and Nrf2 signaling pathway in a Rat Model of High fructose diet induced Steatohepatitis

Document Type : Original Article

Authors

1 Medical Biochemistry department, Faculty of Medicine, Tanta University, Egypt.

2 Clinical Pharmacology department, Faculty of Medicine, Menoufia University, Egypt.

3 Histopathology department, Faculty of Medicine, Tanta University, Egypt.

Abstract

Increased fructose consumption predisposes to nonalcoholic steatohepatitis (NASH).There no effective treatment to be used as the second line when lifestyle modification is insufficient .So, the aim of this study was to evaluate the effect of Curcumin on some biochemical markers in fructose induced NASH . Sixty male albino rats were divided randomly and equally into three groups. Group I (control group). Group II (NASH group), received 70% fructose for 5 weeks .Group III (curcumin treated NASH group), fed as group II followed by daily administration of curcumin at a dose of 50 mg/kg orally for 6 weeks. Blood samples were collected to measure lipid profile, and liver enzymes activities . Liver tissues samples were collected for estimation of mRNA expression levels of nuclear factor E2-related factor-2 (Nrf2) using quantitative real-time PCR ,levels of Beclin 1, AMPK, IL6 and Nrf2 DNA-binding activity by ELISA method, and oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD) ,GSH spectrophotometrically. NASH was confirmed by histopathology as well as increased activity of liver enzymes and marked dyslipidemia .Curcumin ameliorated biochemical disturbance in NASH by upregulating autophagy process through increasing Beclin 1, increasing AMPK and hampered IL6 levels in the liver . It also restored redox balance as evident by suppressing MDA formation and preservation of intracellular antioxidants status via increasing GSH, activating SOD and Nrf2 signaling pathway. Results suggested that curcumin has an effective role in counteracting both abnormalities in autophagy process and redox balance, supporting the potential utility of this natural product in effective treatment of NASH.

Keywords

Main Subjects