L-Carnitine ameliorates immunological-induced hepatitis in rats

Immunological mediated hepatitis can be initiated by bacterial product; Lipopolysaccharide [LPS]. The later is increased during severe infection, bacterial overgrowth or translocation. LPS stimulates Kupffer cells. Activation of the kupffer cells contributes to the onset of liver injuries by producing and releasing cytotoxic agents, inflammatory cytokines and reactive oxygen species. In the present study, L-carnitine, a natural antioxidant and immunoprotective agent, is used to protect against LPS-induced hepatitis. Liver content of glutathione [GSH], malondialdehyde [MDA], nitric oxide [NO] and the DNA adduct S-hydroxydeoxyguanosine [8-HDG] are estimated. Serum activity of liver enzymes ALT, AST, and Gamma-GT, in addition to IL2 level are also estimated. Moreover, liver histopathological changes are determined. Results revealed that LPS [5mg/kg once i.p] significantly increased 8-HDG, MDA, NO and depleted GSH in the liver of the treated rats. It also, increased serum 1L2 and activity of all the estimated liver enzyme markers indicating massive hepatic cellular damage as also shown as a necrotic damage in liver histological sections. LCR administered [500 mg/kg] 3h before LPS protected against LPS-induced lethality by 100%. LCR also prevented the increase in liver content of 8-HDG, MDA and NO. It rescued the depleted GSH and prevented the necrotic damage in the liver tissue as shown by normalization of ALT, AST and Gamma-GT as well as IL2 and a remarkable improvement in liver histology. These data suggest that LCR could be used as an adjuvant therapy in severely infected and septic patients to counteract LPS-induced liver hepatitis

Alpha-lipoic acid counteracts the promoted oxidative DNA damage in the liver of septic rats

Viral, parasitic infections and chemical carcinogens are among the etiological factors of liver cancer. It seems important to study the initiating and promoting agents to evaluate the etiology and prevention of such life threatening disease. Intestine-derived bacterial product, lipopolysaccharide [LPS], is mainly detoxified by the liver. It has shown to induce a state of oxidative stress in the liver but its capability to induce oxidative DNA damage is not fully investigated. Increased oxidative DNA damage and rate of cell proliferation may initiate or even promote cancer. In the present work, the capability of LPS to induce 8-hydroxydeoxyguanosine [8-HDG], a specific DNA adduct for oxidative DNA damage, in rat livers is tested. Furthermore, a possible protective effect of alpha lipoic acid [ALA] is also assessed. Investigated parameters are liver contents of glutathione [GSH], lipid peroxides [MDA], nitric oxide [NO] and 8-HDG in the liver-extracted DNA. Serum activities of ALT, AST, and GGT as liver-function markers as well as serum IL2 are assessed. Moreover, liver histology is examined. LPS was given in doses of 1,3,5,7 and 9 mg/kg once i.p while, the rat mortality was examined 24hrs later. ALA was given in doses of 50,100 and 200 mg/kg once i.p 3h before LPS. LD50 of LPS is found to be 5 mg/kg. LPS increased the level of 8-HDG, MDA and NO in the liver. It also induced an acute liver necrosis and inflammatory cell infiltration as shown in liver-histopathology and in the significant increase in the activities of ALT, AST and GGT. LPS increased the serum level of IL2 as well. The dose 200 mg/kg of ALA revealed a 100% protection against LPS-induced lethality. It also, prevented the LPS-induced increase in 8-HDG in liver-extracted DNA, the liver contents of MDA and NO. ALA also rescued the LPS-induced GSH depletion. It corrected the liver function as shown by the prevention of the increases in the activity of ALT, AST and GGT with a remarkable improvement in liver histology. Moreover, it prevented the increase in serum level of IL2. These data illustrate that LPS can induce oxidative DNA damage which can be prevented by ALA suggesting a potential role for ALA as an adjuvant therapy in a plethora of liver disorders