Antioxidant and anti-inflammatory effects of mild hypothermia in the attenuation of liver injury due to azoxymethane toxicity in the mouse.
Previous studies have demonstrated protective effects of mild hypothermia following acetaminophen (APAP)-induced acute liver failure (ALF). However, effects of this treatment in ALF due to other toxins have not yet been fully investigated. In the present study, the effects of mild hypothermia in relation to liver pathology, hepatic and cerebral glutathione, plasma ammonia concentrations, progression of encephalopathy, cerebral edema, and plasma proinflammatory cytokines were assessed in mice with ALF resulting from azoxymethane (AOM) hepatotoxicity, a well characterized model of toxic liver injury. Male C57BL/6 mice were treated with AOM (100 microg/g; i.p.) or saline and sacrificed at coma stages of encephalopathy in parallel with AOM mice maintained mildly hypothermic (35 degrees C). AOM treatment led to hepatic damage, significant increase in plasma transaminase activity, decreased hepatic glutathione levels, and brain GSH/GSSG ratios as well as selective increases in expression of plasma proinflammatory cytokines. Mild hypothermia resulted in reduced hepatic damage, improvement in neurological function, normalization of glutathione levels, and selective attenuation in expression of circulating proinflammatory cytokines. These findings demonstrate that the beneficial effects of mild hypothermia in experimental AOM-induced ALF involve both antioxidant and anti-inflammatory mechanisms.
Bémeur
Chantal
C
Neuroscience Research Unit, St-Luc Hospital (CHUM), University of Montreal, 1058 St-Denis Street, Montreal, Quebec, Canada, H2X 3J4.
Desjardins
Paul
P
Butterworth
Roger F
RF
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001397:Azoxymethane / Q000633:toxicity; D001929:Brain Edema / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D002273:Carcinogens / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016166:Free Radical Scavengers / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007036:Hypothermia, Induced / Q000379:methods*; D017114:Liver Failure, Acute / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology*; D000637:Transaminases / Q000378:metabolism; D016896:Treatment Outcome
D000975:Antioxidants; D002273:Carcinogens; D016207:Cytokines; D016166:Free Radical Scavengers; D000637:Transaminases; D005978:Glutathione; D001397:Azoxymethane