Alpha-Ketoglutarate Attenuates Endotoxin/D-Galactosamine-Induced Acuteliver Injury in Mice
LÜ Xiaohui, ZHANG Yuxin, LI Sijia, GONG Duoyun, ZHANG Li, TANG Li*
The paper aimed to explore the effect of alpha-ketoglutarate on the occurrence and development of acute liver injury induced by LPS (lipopolysaccharide) and D-Gal (D-galactosamine) and the underlying mechanism. Experimental groups: Control, AKG group, LPS/D-Gal group, LPS/D-Gal+AKG group. In male BALB/c mice, acute liver injury was induced by intraperitoneal injection of LPS/D-Gal. Alpha-ketoglutarate was injected intraperitoneally 0.5 h prior LPS/D-Gal. The mice were sacrificed at 6 h after LPS/D-Gal challenging, and plasma samples were collected for measuring the level of plasma transaminase by colorimetry to evaluate the liver injury. The pathological changes of liver tissue were observed by HE staining. The activities of caspase-3, caspase-8 and caspase-9 were detected by colorimetry. The apoptotic cell was estimated by TUNEL assay, and the level of cleaved caspase-3 was detected by Western blot to imply hepatocyte apoptosis. The results showed that alpha-ketoglutaratetreated LPS/D-Gal-exposed mice had significantly down-regulated incidence of histologic lesions, lower plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase). Treatment with alpha-ketoglutarate also reduced cleaved caspase-3 and caspase-3, caspase-8, caspase-9 activities and reduced the count of TUNEL-positive hepatocytes. Alpha-ketoglutarate can attenuate the pathological changes of acute liver injury induced by LPS/D-Gal and exert the protective effect of anti-apoptosis.
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