Graduate Thesis Or Dissertation
 

The effect of hypothermia on biochemical and morphological aspects of carbon tetrachloride hepatotoxicity

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  • The temporal relationships among selected correlates of hepatocellular damage were investigated in cordotomized, hypothermic rats intoxicated with carbon tetrachloride (CC1₄). Rats were spinally transected between C6 and C7 and allowed to become hypothermic. CC1₄ (1.25 ml/kg ip) was administered as a 1:1 solution in corn oil. Plasma alanine aminotransferase (ALT) activity and bilirubin concentrations, hepatic malondialdehyde (MDA) formation, glucose-6-phosphatase (G6Pase) activity, and microsomal diene conjugations, as well as morphological changes were monitored over a 48-hour time course. Diene conjugation, ALT and morphologic changes were all delayed and attenuated in CC1₄ treated transected rats. The depression of hepatic G6Pase after CC1₄ treatment was of the same magnitude in both transected and non-transected rats and was delayed only slightly in the cordotomized animals. Elevation of plasma bilirubin was delayed in transected rats, but the magnitude of the response was greater than that seen in nontransected rats. Parallel increases in MDA occurred in both CC1₄ and corn oil treated transected rats over the 48-hour period. These results demonstrate that spinal cord transection has differential influences upon the developing hepatotoxic effects of CC1₄. Thus, the hypothermic rat may provide a model for a more detailed examination of the relationships among events associated with toxic hepatocellular degeneration.
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