cyclic-gmp and Chemical-and-Drug-Induced-Liver-Injury

Changes of some immune-mediators in liver tissue homogenate and plasma of liver injury mice injected with CCl4 and its mechanism in the liver injury process induced by CCl4 were studied. Thirty healthy mice with half of female and male were chosen and divided randomly into two groups which were control group (group C) and CCl4-injecting group (group CCl4). The liver injury was induced by abdominal injection of CCl4 (0.07 ml/100 g body weight) on every other day over six weeks. The blood and liver were collected at the 2nd, 4th and 6th week, respectively, and liver homogenate cAMP, cGMP levels and MDA concentration as well as plasma IL-2 and TNF-alpha levels were determined. The results show that during the entire experimental period, cAMP level decreased or markedly decreased in group CCl4. After the 2nd week of CCl4-injecting, cGMP was lower or significantly lower in group CCl4 than in group C; cAMP/cGMP ratio tended to drop, and was low or significantly low to group C; and MDA content was significantly higher in group CCl4 than in group C. During the whole experimental period, a marked decrease of plasma IL-2 in group CCl4 was seen, and plasma TNF-alpha of group CCl4 was superior to that of group C. It is suggested that the violent changes of immune-mediators including cAMP, cGMP, TNF-alpha and IL-2 etc induced by CCl4 may play an important role in the induction of liver injury in mice.

Topics: Animals; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cyclic AMP; Cyclic GMP; Female; Interleukin-2; Liver; Male; Malondialdehyde; Mice; Random Allocation; Tumor Necrosis Factor-alpha

Rats having a non-necrotic damaged liver or a necrotic damaged liver produced by D-galactosamine administration were restrained in water for 0.5, 1, 2, 4, 6, 8 and 12 hours. Serial changes in intrahepatic energy metabolism were compared with those in normal liver. Energy charge, which represents the degree of equilibrium between the energy producing and consuming systems, and cyclic AMP, an intracellular messenger mediating the action of hormones, showed biphasic increases before and after 2 hr in the damaged livers. The lactate/pyruvate ratio, which reflects the cytosolic redox state, markedly increased at 0.5 hr in the damaged livers but returned to the pre-stress level after 1 hr in the non-necrotic damaged liver and after 4 hr in the necrotic damaged liver, showing a transient reduced state. The beta-hydroxybutyrate/acetoacetate ratio, which represents the mitochondrial redox state, decreased at 0.5 hr and returned to the pre-stress level at 1 hr in the non-necrotic damaged liver, exhibiting a transient oxidized state. However, in the necrotic damaged liver, the value decreased at 0.5 hr remained low thereafter, demonstrating a persistent oxidized state. These findings show that, in severely damaged liver, stress has more marked effects on hepatic energy metabolism.

Topics: Acetyl Coenzyme A; Animals; Chemical and Drug Induced Liver Injury; Cyclic AMP; Cyclic GMP; Energy Metabolism; Galactosamine; Ketone Bodies; Lactates; Lactic Acid; Liver Diseases; Male; Pyruvates; Pyruvic Acid; Rats; Rats, Inbred Strains; Stress, Physiological