Abstract
Aim: To determine the potential hepatoprotective effect of Agmatine (AGM) on NAFLD-induced by Type 2 diabetes mellitus (T2DM) in rats.
 Study design: Forty male Wistar rats weighing from (200 -250 g) were distributed at random into five groups (8 rats per group): group 1 as control; group 2 as untreated-T2DM; groups 3 & 4 as T2DM cotreated with AGM (40 & 80 mg/kg/d), while group 5 T2DM cotreated with Silymarin (100 mg/kg/d).
 Place and duration of study: Department of Pharmacology, Faculty of Medicine, king Abdul-Aziz University; between October 2020 and January 2021.
 Methodology: A rat model of T2DM with NAFLD complication was established by feeding rats with 10% fructose in drinking water and intraperitoneally injecting them with a single low dose of streptozotocin (STZ) (45mg/kg). The fasting blood glucose was detected, serum levels of hepatic biomarkers were all assessed. Moreover, histopathological examination was performed by hematoxylin and eosin (H&E) staining.
 Results: STZ induced T2DM in rats causes a significant (p<0.05, n=8) rise in serum levels of FBG, ALT, AST, TB, TC, TG, and LDL in comparison with the corresponding control group. Co-treatment with AGM (40 & 80 mg/kg) and silymarin significantly alleviated hyperglycemia and amended hepatic biomarkers that was reflected on improved histopathological changes.
 Conclusion: The current data suggest that oral AGM co-treatment could have a hepatoprotective effect against T2DM associated with NAFLD in rats. Further investigations are recommended to elucidate molecular mechanisms accountable for the useful effects of AGM on hepatocytes.
Highlights
The liver is one of the primary organs that control the metabolic homeostasis
Co-treatment with AGM (40 & 80 mg/kg) and silymarin significantly alleviated hyperglycemia and amended hepatic biomarkers that was reflected on improved histopathological changes
The current data suggest that oral AGM co-treatment could have a hepatoprotective effect against Type 2 diabetes mellitus (T2DM) associated with NAFLD in rats
Summary
The liver is one of the primary organs that control the metabolic homeostasis. Metabolic diseases such as IR, T2DM, dyslipidemia, and NAFLD are linked through molecular-biochemical, and complex immune mechanism [1]. Both NAFLD and diabetes are chronic diseases that usually delineate nonalarming changes that can lead to disorder and many other metabolic complications [2]. They are all independently mortality and morbidity risk enhancers, and overall global financial consumer disorders [3]. There is a strong association between NAFLD and T2DM risk [4].
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