ABSTRACT
In vitro studies have suggested that sporidesmin hepatotoxicity may be related to thiol oxidation and generation of cytotoxic oxygen species. After a single i.p. injection of 2.8 mg/kg bw sporidesmin in guinea-pigs, hepatic and plasma zinc, hepatic metallothionein, cytochromes P-450 and b5, total glutathione and proteins (total, microsomal and cytosolic) were monitored for 21 days. The only variations observed were significant increases in liver concentrations of zinc (cytosolic and total), metallothionein, and cytochromes, which peaked on day 8 after the sporidesmin challenge (+45, 55, 50, 376 and 413%, respectively) and, except for cytochrome b5, went back to control levels before the 21st day. These results suggest that cytochromes P-450 and b5 may be involved in sporidesmin cellular damage.
Subject(s)
Cytochrome P-450 Enzyme System/analysis , Cytochromes b5/analysis , Liver/chemistry , Metallothionein/analysis , Sporidesmins/pharmacology , Zinc/analysis , Animals , Guinea Pigs , Injections, Intraperitoneal , Male , Sporidesmins/administration & dosageABSTRACT
Sporidesmin, a hepatotoxin from Pithomyces chartarum, is responsible for facial eczema in ruminants. In an attempt to clarify the biochemical processes supporting sporidesmin toxicity and response of the liver, haematology, plasma biochemistry and liver enzyme changes were monitored for 21 days in a model for facial eczema resulting from a single intraperitoneal injection of 2.8 mg/kg BW sporidesmin to guinea pigs. Most plasma disturbances were observed 8 days after administration and accounted for starvation, liver cytolysis, and cholestasis or liver enzyme induction. Alterations of hepatic enzyme activities were intense with a maximum increase on days 2 for alkaline phosphatases (ALP) and 8 for gamma-glutamyltransferase (GGT), and a maximum decrease on day 21 for aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT). Comparison of liver and plasma enzyme changes indicates that GGT was the most reliable and significant plasma indicator of sporidesmin-associated liver alterations. Moreover, this study points out the validity of the one-dose intoxicated guinea-pig model for research on sporidesmin biochemical toxicity and pathobiology of facial eczema.
