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

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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.

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Acknowledgments

M.R.B.B is a post-graduate student in Cellular and Molecular Biology (PUCRS), supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior). L.F.L is an undergraduate Pharmacy student holding a fellowship from the Institution (BPA Program—PUCRS).

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Authors and Affiliations

  1. Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, RS, Brazil

    Mariel R. B. Betto

  2. Institute of Toxicology and Pharmacology, PUCRS, Avenida Ipiranga, 6681, Partenon, 90619-900, Porto Alegre, RS, Brazil

    Lais F. Lazarotto, Carlos E. Leite & Maria M. Campos

  3. School of Pharmacy, PUCRS, Porto Alegre, RS, Brazil

    Lais F. Lazarotto

  4. Department of Veterinary Pathology, UFRGS, Porto Alegre, RS, Brazil

    Tatiane T. N. Watanabe & David Driemeier

  5. School of Dentistry, PUCRS, Porto Alegre, RS, Brazil

    Maria M. Campos

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  1. Mariel R. B. Betto
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Correspondence to Maria M. Campos.

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Betto, M.R.B., Lazarotto, L.F., Watanabe, T.T.N. et al. Effects of treatment with enalapril on hepatotoxicity induced by acetaminophen in mice. Naunyn-Schmiedeberg's Arch Pharmacol 385, 933–943 (2012). https://doi.org/10.1007/s00210-012-0774-7

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  • DOI: https://doi.org/10.1007/s00210-012-0774-7

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