cyclic-gmp and Carbon-Tetrachloride-Poisoning

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

Treatment of rats with two different doses of CCl4 (respectively 2.5 and 0.5 ml/kg body wt. intragastrically) is followed by a rapid increase in the cAMP content of the liver. With 0.5 ml of CCl4, the increase occurs as early as 30 min after poisoning, namely about 4-5 h before the onset of triglyceride accumulation in the liver. The maximum increase has been at 6 h after administration of the hepatotoxin. In both experimental conditions, normal values are recovered only after 36-48 h. cGMP level appears unmodified during the whole observation period. Therefore the ratio cGMP/CAMP decreases consistently. The ATP level decreases significantly between 2 and 12 h. The increase in liver triglycerides level after CCl4 can be also a consequence of an impairment of microtubule function, leading to a decreased release of lipoprotein micelles from hepatocytes into the blood stream.

Topics: Adenosine Triphosphate; Animals; Carbon Tetrachloride Poisoning; Cyclic AMP; Cyclic GMP; Dose-Response Relationship, Drug; Liver; Male; Rats; Triglycerides