Development of eosinophil peroxidase activity and concomitant alteration of the antioxidant defenses in the liver of mice infected with Schistosoma mansoni.
OBJECTIVE
The tropical parasite Schistosoma mansoni causes granulomatous inflammation following lodging of eggs in portal capillaries. In vitro studies indicated that the host reaction should involve reactive oxygen intermediates; however, it is not known what occurs in vivo at the site of the disease. Moreover, the ultimate pathophysiological effects of oxidative processes depend upon antioxidant factors, which are investigated in this study.


METHODS
We explored the changes in the major enzyme activities involved in liver redox metabolism during the course of infection and, for some of them, the mRNA expression. We also measured the reduced glutathione and lipid peroxide levels in the liver.


RESULTS
We found that the deposition of parasite eggs triggers the release of endogenous eosinophil peroxidase; enzyme activity developed in the immediate vicinity of the eggs and it increased dramatically with time. However, Cu,Zn-superoxide dismutase, catalase and glutathione peroxidase activities decreased drastically. In contrast, glutathione transferase was unaffected. There was no proportional decrease in mRNA levels for the H2O2 scavenging enzymes. Reduced glutathione concentrations also dropped as a result of infection. Lastly, a two-fold increase in the levels of hepatic products generated by lipid peroxidation was observed.


CONCLUSIONS
These results show that on the one hand oxidative processes occurred at the site of granulomatous inflammation and on the other hand the antioxidant capacity of the liver decreased, leading to the generation of lipid peroxides. The resulting imbalance between pro- and anti-oxidant processes may play a central role in the pathology associated with schistosomiasis.
Gharib
B
B
INSERM U399, Univ. Mediterranee, Marseille, France.
Abdallahi
O M
OM
Dessein
H
H
De Reggi
M
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D004804:Eosinophils / Q000201:enzymology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D010063:Ovum / Q000166:cytology; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012555:Schistosomiasis mansoni / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D000975:Antioxidants; D012333:RNA, Messenger; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione