RESUMO
We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.
Assuntos
Animais , Feminino , Acetaminofen , Analgésicos não Narcóticos , Falência Hepática Aguda , Teníase/parasitologia , Acetaminofen/administração & dosagem , Alanina Transaminase/sangue , Analgésicos não Narcóticos/administração & dosagem , Biomarcadores/sangue , Citocromo P-450 CYP2E1/biossíntese , Citocromo P-450 CYP2E1/sangue , Modelos Animais de Doenças , Hepatócitos/parasitologia , Hepatócitos/patologia , Interleucina-5/sangue , Interleucina-6/sangue , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/parasitologia , Falência Hepática Aguda/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Teníase/patologiaRESUMO
Fulminant liver failure due to visceral leishmaniais is very rare, and has been described only in children. We report an immunocompetent adult man who developed acute liver failure due to leishmaniais and dramatically recovered with amphotericin-B therapy.