Cyclosporin A protects Balb/c mice from liver damage induced by superan tigen SEB and D-GalN.
AIM:To investigate the pathogenic effect of SEB and D-GalN on liver and the protection of cyclosporin A, the relationship between hepatic apoptosis and necrosis and the possible mechanism of acute hepatic necrosis.METHODS:After staphylococcal enterotoxin B (SEB) mixed with D-galactosamine (D-GalN) were injected intraperitoneally into Balb/c mice and those previously treated with cyclosporin A, blood samples were collected and livers were isolated at 2, 6, 12, 24h. Patterns of hepatocellular death were studied morphologically and biochemically, circulating cytokines (TNF-alpha, IFN-gamma) and mice mortality within 24h was assessed.RESULTS: The SEB could induce the typical apoptotic changes of hepatocytes, the D-GalN could induce hepatocytes apoptosis and degeneration at the same time, and the mice having received the SEB+D-GalN injections developed apoptosis at 2 and 6h, but after 12h hepatocytes were characterized by severe injury, whereas all the examinations in the cyclosporin A treated mice were normal.CONCLUSION:Hepatic cell apoptosis might be related to necrosis, and massive hepatocyte apoptosis is likely the initiating step of acute hepatic necrosis in mice. The effects induced by SEB and D-GalN on hepatocytes might be mediated by T cells, and could be prevented by cyclosporin A.
Yin
Tong
T
Tong
Shan-Qing
SQ
Xie
Yu-Cai
YC
Lu
De-Yuan
DY