Co-Administration of Morphine and Naloxone: Histopathological and Biochemical Changes in the Rat Liver

Abstract

Background: Co-administration of opioid agonists and antagonists at low doses has been reported to significantly enhance and/or prolong the analgesic effects and reduce or prevent tolerance to or dependence on opioids. Objectives: The current study aimed at evaluating the naloxone effect on morphine-induced histopathological and hematologic changes in rats. Materials and Mehods: Thirty mature male Wistar rats were categorized into three groups (n = 10) in a random manner, including the control group receiving normal saline, the morphine-sole group receiving morphine (5 mg/kg/day), and morphine + naloxone group receiving morphine and naloxone (5 and 0.4 mg/kg/day, respectively). After 50 days, the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), triglyceride (TG), aspartate aminotransferase (AST), cholesterol, and high-density lipoprotein (HDL) were measured in the serum. Moreover, the levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPx) were measured to assess the serum antioxidant capacity. Histopathological changes were investigated via hematoxylin and eosin, Masson’s trichrome, and periodic acid-Schiff staining. Inter-group comparisons were made by GraphPad Prism software using one-way ANOVA and Tukey’s test. Results: The animals in the morphine + naloxone group showed higher AST, ALP, ALT, and CAT levels in comparison with the control and morphine-sole groups (P < 0.05). Our findings revealed no changes in the cholesterol, TG, SOD, and GPx levels among the groups (P > 0.05). However, the morphine-sole group exhibited higher serum levels of HDL compared with the controls (P < 0.05). The morphine-sole group showed fibrosis, local necrosis, immune cell infiltration, and diminished intra-cytoplasmic carbohydrate storage. Conclusions: The findings suggest that apart from unchanged serum markers, morphine can potentially induce hepatotoxicity, and at the same time, naloxone is able to ameliorate morphine-induced histopathological damages.