A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6.
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.
Centro de Investigación Científica y de Educación Superior de Ensenada, Departamento de Innovación Biomédica, Baja California, México.
Marco A
MA
De León-Nava
Centro de Investigación Científica y de Educación Superior de Ensenada, Departamento de Innovación Biomédica, Baja California, México.
Carolina
C
Álvarez-Delgado
Centro de Investigación Científica y de Educación Superior de Ensenada, Departamento de Innovación Biomédica, Baja California, México.
Luis
L
Donis-Maturano
Universidad Nacional Autónoma de México, Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Hospital General de México Dr Eduardo Liceaga, Laboratorio de Hígado, Páncreas y Motilidad, Ciudad de México, México.
Joselin
J
Hernández-Ruiz
Universidad Nacional Autónoma de México, Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Hospital General de México Dr Eduardo Liceaga, Laboratorio de Hígado, Páncreas y Motilidad, Ciudad de México, México.
Aaron N
AN
Manjarrez-Reyna
Universidad Nacional Autónoma de México, Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Hospital General de México Dr Eduardo Liceaga, Laboratorio de Hígado, Páncreas y Motilidad, Ciudad de México, México.
Edgar
E
Cruz-Avilés
Universidad Nacional Autónoma de México, Facultad de Estudios Superiores-Iztacala, Unidad de Biomedicina, Carrera de Médico Cirujano, Los Reyes Iztacala, México.
Sonia
S
Leon-Cabrera
Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Departamento de Inmunología, Ciudad de México, México.
Jorge
J
Morales-Montor
Instituto Nacional de Cardiología Ignacio Chávez, Departamento de Biología Molecular, Ciudad de México, México.
José M
JM
Fragoso
Universidad Nacional Autónoma de México, Facultad de Medicina, Unidad de Investigación en Medicina Experimental, Hospital General de México Dr Eduardo Liceaga, Laboratorio de Hígado, Páncreas y Motilidad, Ciudad de México, México.
Galileo
G
Escobedo
D000082:Acetaminophen / Q000008:administration & dosage; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000818:Animals; D015415:Biomarkers / Q000097:blood; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D022781:Hepatocytes / Q000469:parasitology / Q000473:pathology; D015848:Interleukin-5 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000401:mortality / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013622:Taeniasis / Q000469:parasitology* / Q000473:pathology
D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D015848:Interleukin-5; D015850:Interleukin-6; D000082:Acetaminophen; D019392:Cytochrome P-450 CYP2E1; D000410:Alanine Transaminase