|Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
A mitochondria-rich fracion isolated from the livers of ICR and C3H female mice 8 to 10 weeks after Schistosoma mansoni infection showed to be uncoupling state of the succcinateーsupported respiration. A moderate to strong mitochondrial Mg^<++>-dependent ATPase activity at neutral pH was demonstrated cytochmecally in the parenchymal liver cells of S. mansoni-infected mice. Moreover, the enzymatic activities of malate dehydrogenase, NADH dehydrogenase, cytochrome oxidase and glutamate dehydrogenase also decreased significantly in the mitochondria-rich fraction from the livers of infected mice. Furthermore, an ultrastructural observation of the liver of infected mice clearly demonstrated some morphological changes of hepatic mitochondria, i. e., swelling, disappearance of cristae and deciline of electron density of matrix.
The uncoupling state of the respiration and the ultrastructural changes of the hepatic mitochondria were also demonstrated in the uninfected, normal mice treated with in
traperitoneal injection of the dialysate of 15,000g x 30 min supernatant of crude extracts of egg-granulomas. However, there was no appreciable change in the respiration of hepatic mitochondria in the mice treated with culture fluid or crude extract of S. mansoni adult worms. The active substance was partially purified from crude extract of egg-granulomas by ammonium sulfate fractionation, Sephadex G-200 gel filtration and DEAEーsephadex A-25 column chromatography. Intraperitoneal injection of the partially purified substance into unifected, normal mice resulted in the decline of the activities of several enzymes in hepatic metochondria and in the ultrastructural changes in the mitochondria of parencymal liver cells. The same biochemical changes were also observed in the primary cultured hepatocytes treated with the partially purified substance.
These findings suggest that the egg-granulomas produce some substance(s) which may be responsible for reduction of the activities of respiration and several enzymes localized in the mitochondria of the parenchymal liver cells in S. mansoni-infected mice. Less