Abstract

Aim:The current study was designed to evaluate the potential hepatoprotective and immunomodulatory effects of copper-nicotinate complex (CNC) against methionine- and choline-deficient diet (MCDD)-induced fatty liver in rats.Materials and Methods:Forty male Wistar rats were randomly allocated into one of four equal-sized groups (G1-G4). The G1 group was fed a balanced diet and kept under normal conditions; the G2 group received CNC orally at a dose of 0.043 mg/kg body weight, 3 times/week for 4 weeks, and a balanced diet; the G3 group was fed an MCDD for 4 weeks; and the G4 group was fed an MCDD and administered CNC at the same dose and route as G2. Blood samples were collected for the determination of serum enzyme activity. After 4 weeks of treatment, liver specimens were collected for the evaluation of the oxidative/antioxidative markers, cytokine gene expression, and histopathological examination.Results:CNC improved MCDD-induced liver dysfunctions by recovering serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities to their normal levels. The glutathione (GSH) level and superoxide dismutase (SOD) activity significantly decreased, while lipid peroxidation (as reflected by malondialdehyde [MDA]) markedly increased in the liver tissue of the MCDD group. After cotreatment with MCDD and CNC, the GSH level and SOD activity markedly increased and the MDA level significantly decreased to return to normal levels. After cotreatment with MCDD and CNC, significant downregulation of the mRNA expression of hepatic interleukin (IL)-1β, IL-4, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1 genes was found. Moreover, CNC reduced fatty liver complications by reducing the number of hepatic vacuolations, degenerative changes in the hepatocytes, and hemorrhage.Conclusion:CNC has the potential to limit tissue injury and possibly prevent the progression to severe liver disease caused by an MCDD.

Highlights

  • Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder across the world

  • After cotreatment with methionine- and choline-deficient diet (MCDD) and coppernicotinate complex (CNC), the GSH level and superoxide dismutase (SOD) activity markedly increased and the MDA level significantly decreased to return to normal levels

  • On the other hand, when compared to both the control (G1) and CNC alone (G2) groups, the group fed with MCDD and cotreated with CNC (G4) showed recovery of ALT, AST, and gamma-glutamyl transferase (GGT) levels to normal values (Table-4)

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Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder across the world. It has a prevalence of approximately 20% in the general population and up to 95% in people with obesity. This liver disease includes mild-to-severe steatosis, steatohepatitis, hepatocellular injury, progressive chronic inflammation, and fibrosis [1]. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

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