Sulfobromophthalein disposition in rainbow trout (Salmo gairdneri) as influenced by carbon tetrachloride intoxication Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/qb98mh557

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  • Clinical methods to diagnose specific organ dysfunction have not been evaluated in fishes. To determine if an accepted clinical test of mammalian liver function could be applied to fishes, the hepatic disposition of the organic anion sulfobromophthalein (BSP) was studied in rainbow trout (Salmo gairdneri) treated with a model hepatotoxicant. Carbon tetrachioride (CCl₄) was used to model liver damage in the trout because t is widely used in this capacity in mammalian studies. The initial objective was to evaluate the importance of the liver of the trout in the elimination of BSP. As in mammals, hepatic BSP accumulation in the rainbow trout appeared to be the most important factor contributing to plasma clearance of the dye while biliary excretion was the rate limiting step in the overall transfer of BSP from plasma to bile. Differences between trout and other species with respect to rates of plasma clearance, hepatic accumulation, and biliary excretion of BSP could be explained when anatomical and physiological differences were considered. The next objective was to determine the value of CCl₄ as a potential hepatotoxic agent in rainbow trout. Plasma haif-lifes of BSP increased in proportion to the dose of CCl₄ administered and histological examination of liver sections indicated that morphological damage, including necrosis of hepatocytes surrounding central veins, also occurred following intoxication. In addition, hemoglobinemia was observed in fish as early as 12 h after treatment. To determine if high concentrations of hemoglobin hd influenced the rate of BSP clearance, plasma clearance studies were conducted In two groups of fish following prolonged infusion of either hemoglobin or bilirubin. Results of these studies indicated that plasma BSP clearance was not affected by high plasma levels of either compound and it was therefore concluded that the CCl₄ induced plasma retention of BSP in the trout could not be explained by the intravascular hernolysis which attended the intoxication. The final objective was to attempt to establish how CCl₄ intoxication was acting to induce plasma BSP retention. To determine if CCl₄ treatment had impaired hepatic processes associated with biliary BSP excretion, bile flow, bile BSP concentration and percent of metabolized BSP appearing in the bile were determined in treated and control animals during prolonged, graded infusion of the dye. Results these studies indicated that, unlike mammals, components of the hepatic excretory process were not impaired 24 h after CCl₄ treatment. Additional studies indicated that the rate of hepatic BSP accumulation following injection of a single dose of the dye was reduced in treated animals and suggested that processes of hepatic uptake and storage may have been impaired. These studies indicate that the organic anion sulfobrompphthalein is a useful compound with which to study liver function in trout. Furthermore, a test of liver dysfunction based on the rate of plasma BSP clearance may prove to be a useful method by which to diagnose liver damage in this fish.
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