Drug Design, Development and Therapy (Nov 2018)
Histopathological study of liver tissue due to methadone consumption and its effect on liver enzymes and inflammatory indices in rat
Abstract
Mansour Amraei,1,* Mahmoud Mohamadpour,2,* Mohammad Reza Hafezi Ahmadi,3 Monireh Azizi,4 Ahmad Daemi,5 Mohammad Omidi,5 Ehsan Shirzadpour2 1Department of Physiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran; 2Department of Biochemistry, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran; 3Department of Pathobiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran; 4Department of Anatomy, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran; 5Department of Biochemistry, Student Research Committee, Ilam University of Medical Sciences, Ilam, Iran *These authors contributed equally to this work Background: Methadone (MET)-based treatment is currently one of the best known approaches in the treatment of opioid dependence. It is claimed that MET use exerts adverse effects on the performance of some organs, especially liver. Thus, the present study aims to investigate MET effects on the hepatic tissue as well as its effect on the hepatic enzyme levels and inflammatory markers in rats.Materials and methods: Twenty-eight mature male Wistar rats underwent an 8-week treatment in four equal groups including the control group (an ordinary daily dietary regime) as well as the experimental groups 1, 2, and 3 (an ordinary daily dietary regime and gavage-fed on MET syrup for 5, 20, and 40 mg/kg body weight per day). Blood samples were collected from all rats in the beginning and end of the study to measure their hepatic enzyme levels and inflammatory markers. In the end, their livers were subjected to histological examinations.Results: The mean serum levels of hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) increased considerably across all the three groups that had received various dosages of MET (5, 20, and 40 mg/kg) in the end of the study as compared to the beginning of the study (P<0.001). It was also found that the inflammatory indicators (interleukin-6, tumor necrosis factor-alpha, and C-reactive protein) rose significantly in the groups that had received various dosages of MET in contrast to the control group (P<0.01, P<0.001, and P<0.001, respectively). The histopathological images of the liver cross-sections revealed dosage-dependent tissue changes in the groups that had received various dosages of MET.Conclusion: The present study tried to prove the adverse effects of MET in the development of liver damage. Since MET-based treatment is frequently prescribed by physicians for curing the addiction to narcotics, better strategies are required for its correct usage. Keywords: methadone, hepatic enzymes, inflammatory markers, lipid profile, rat
