Effects of treatment with enalapril on hepatotoxicity induced by acetaminophen in mice

Abstract

There is a current need for new therapeutic options for acetaminophen (APAP)-induced hepatotoxicity. Herein, we assessed the effects of prophylactic and therapeutic treatment with the angiotensin-converting enzyme (ACE) inhibitor, enalapril, on APAP-caused hepatotoxicity. Male and female C57BL/6 J mice were used, and hepatotoxicity was induced by a single application of APAP (400 mg/kg, i.p.). Macroscopic and histological liver alterations, serum alanine transaminase (ALT) and aspartate transaminase (AST) activity, liver catalase activity (CAT), reduced glutathione concentrations (GSH), hepatic measurement of neutrophil migration (myeloperoxidase, MPO activity), and caspase-3 liver expression were evaluated. The prophylactic and the therapeutic treatments with enalapril were able to markedly reduce the macroscopic and histological liver alterations as well as the caspase-3 immunopositivity. Both schedules of treatment were also effective in reducing GSH concentrations as well as neutrophil migration. Conversely, only the pre-treatment (but not the post-administration) with enalapril significantly reversed APAP-induced CAT decrease. Furthermore, the pre- or the post-treatment with enalapril largely reduced ALT and AST serum activity in APAP-intoxicated mice. The hepatoprotective effects of enalapril were comparable to those obtained with the clinically used compound N-acetylcysteine (NAC) when given in a therapeutic regimen. Data obtained with the prophylactic protocol of treatment might indicate that individuals under treatment with ACE inhibitors are less susceptible to the toxic effects of APAP. Additionally, the therapeutic approach allows us to suggest that enalapril might represent an innovative tool for treating APAP intoxication.

High-fat diet effect on periapical lesions and hepatic enzymatic antioxidant in rats

“…Liver samples were homogenized in saline and centrifuged at 3500g for 10 min for analysis of endogenous antioxidant status. CAT activity and GSH levels were determined according to the methodology described previously [29].…”

Protective Effect of Gemfibrozil on Hepatotoxicity Induced by Acetaminophen in Mice: the Importance of Oxidative Stress Suppression

“…Many of these studies have shown that pretreatment or simultaneous treatment with diverse agents can provide protection against APAP hepatotoxicity. 19 , 20 Antioxidant agents have therapeutic potential in drug-induced toxicity. 21 NAC is used as present treatment for APAP toxicity, by replacing cellular GSH to prevent of cell damage by NAPQI.…”

Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury

“…For instance, paracetamol poisoning was shown to increase ALT and AST activities in rabbits (43). Another study on the effects of ACE inhibitor enalapril on paracetamol-induced liver damage has found significantly reduced ALT and AST activities in mice treated with enalapril (44). The present study investigated the effects of another ACE inhibitor, omapatrilat, on ALT and AST activities.…”