Effects of Glucagon-like Peptide-1 Analogues and Dipeptidyl Peptidase-IV Inhibitors on Hepatic Oxidative Stress and Non-Alcoholic Steatohepatitis in Male Albino Rats

  • Osama Mahmoud Mehanna Department of Physiology, Faculty of Medicine, Taif University, KSA. and Department of Physiology, Damietta Faculty of Medicine, Al-Azhar University, EGYPT.
  • Ahmad Abd Elhakam El Askary Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, KSA and Department of Medical Biochemistry, Damietta Faculty of Medicine, Al-Azhar University, EGYPT.
  • Basem Hasan El Esawy Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, KSA and Department of Pathology, Mansoura University, EGYPT.
  • Tarek Mohamed Ali Department of Medical Physiology, College of Medicine, Taif University, KSA and Department of Medical Physiology, Faculty of Medicine, Beni-Suef University, EGYPT.
  • Osama Mohamed Abo-Salem Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, EGYPT.
Keywords: GLP-1 analogues, DPP-IV Inhibitors, Hepatic Oxidative Stress, NASH, Liver function

Abstract

Background and Aim: Due to their importance in glucose metabolism and lipid accumulation, in addition to their prolonged action, overall safety and efficacy; glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-IV inhibitors (DPP-IV inhibitors) are becoming one of the cornerstones for treatment of obesity, T2DM and NASH. This study aimed to distinguish between the effect of both Liraglutide (a long-acting GLP-1 analog) and Sitagliptin (a DPP-IV inhibitor) on nutritional steatohepatitis in adult male rats. Methods: A total of 40 male Sprague-Dawley rats were divided into four groups; the normal control group and the steatohepatitis placebo group; steatohepatitis liraglutide- treated and steatohepatitis sitagliptin-treated groups. Liver weight and functions, lipid profile, glycemic status, hepatic oxidant-antioxidant parameters and histopathological analysis were assessed in comparison with the control rats. Results: Treatment of steatohepatitis in rats with either liraglutide or sitagliptin significantly reduced the levels of blood sugar, insulin, HOMA-IR, hepatic MDA and nitric oxide (NO). Moreover, they significantly increased the antioxidant enzyme activities, improved the histopathological changes compared to the control rats, with slightly superior effects for Liraglutide. Conclusion: Treatment with either GLP-1 RAs or DPP-IV inhibitors improved the hepatocyte viability. Treatment improved the hepatic fatty deposition, attenuated the progression of hepatic fibrosis and reduced the hepatic oxidative stress in male steatohepatitis rats, with slightly superior effects for GLP-1 RAs.

Microscopic examination from the liver tissue of control group showing normal hepatic structure
Published
2020-05-05
How to Cite
Mehanna, O. M., El Askary, A. A. E., El Esawy, B. H., Mohamed Ali, T., & Abo-Salem, O. M. (2020). Effects of Glucagon-like Peptide-1 Analogues and Dipeptidyl Peptidase-IV Inhibitors on Hepatic Oxidative Stress and Non-Alcoholic Steatohepatitis in Male Albino Rats. International Journal of Clinical and Experimental Physiology, 7(1), 27-32. https://doi.org/10.5530/ijcep.2020.7.1.7