Histopathological study of liver tissue due to methadone consumption and its effect on liver enzymes and inflammatory indices in rat

Abstract

BackgroundMethadone (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 methodsTwenty-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.ResultsThe 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.ConclusionThe 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.

Hepatotoxic Effects Due to the Combined Consumption of Opioid Drugs and Alcohol

“…By activating cytochrome P-450-dependent monooxygenases, opioids deplete the system of cytochromes and activate free-radical processes. In turn, the peroxidation of cell membrane lipids as a result of the action of free radicals leads to damage to the membrane of hepatocytes, which, in turn, can cause the loss of intracellular cytosolic components with the subsequent increase in the activity of plasmatic transaminases and a decrease in the pool of hepatocellular glutathione [3][4][5]. It has also been established that δ-opioid receptors, which are known to make a significant contribution to cellular development and are abundant in liver tissue, influence the initiation and progression of liver diseases in drug users [8].…”

“…Histopathologic examination of hepatocytes obtained from chronic opioid-treated rat models showed sinusoidal dilatation, perivenular ballooning degeneration, perivenular necrosis, haemorrhage, and focal microvascular steatosis. Animal studies demonstrate that long-term administration of opioids initiates the occurrence of dystrophic-inflammatory processes in the liver tissue, which are significantly intensified against the background of alcohol consumption and are manifested in the form of dilation or narrowing of sinusoids, hemostasis with the formation of blood clots and haemorrhages, hypertrophy, and eventually dystrophy of hepatocytes, in which hydropic dystrophy, lymphohistiocytic infiltration, focal necrosis and an increase in the number of altered apoptotic cells predominate [5].…”

“…The most widespread combination was «street methadone» and alcohol. Mechanisms of hepatotoxic effects of synthetic opioids (heroin, methadone) and alcohol were previously studied in experiments on human cultured hepatocytes and rats [4,5]. However, the peculiarities of the development of hepatotoxicity in the case of combined human consumption of modern synthetic drugs and alcohol have not been sufficiently studied.…”