ABSTRACT
This study was designed to evaluate the lactate production by isolated hepatocytes in rats with cirrhosis induced by means CCl4 + ethanol and the effect of colchicine in this experimental model of fibrosis. The effect of colchicine on lactate metabolism may be important in explaining the beneficial mechanism of this therapy on liver cirrhosis. Colchicine treatment produced a decrease in perivenular fibrosis and a descense in the degrees of this histological lesion. Colchicine treatment ameliorated the subsequent further development of cirrhosis. Lactate production in colchicine groups were higher than the carbon tetrachloride groups. By contrast, a priori, we observed a decrease in lactacidaemia and a lesser lactate utilization in colchicine groups comparison with CCl4 + ethanol groups. Our results suggest that colchicine improves the fibrosis by a mechanism independent of hepatic lactate metabolism.
Subject(s)
Carbon Tetrachloride Poisoning/pathology , Chemical and Drug Induced Liver Injury/pathology , Colchicine/pharmacology , Lactates/metabolism , Liver Cirrhosis, Alcoholic/pathology , Animals , Cells, Cultured , Lactic Acid , Liver Function Tests , Male , Rats , Rats, WistarABSTRACT
Lactic acidosis has been described in patients with liver disease. Hyperlactacidaemia results from an imbalance in lactate production versus lactate utilization. It is estimated that the liver utilizes approximately 30 percent of the total lactate produced in the body under basal conditions, primarily by gluconeogenesis. The gluconeogenesis from lactate 10 mM and lactacidaemia were determined in order to investigate the effects of CCl4+ethanol administration in liver injury and, the possible effect of colchicine in our experimental fibrosis model. The tests were determined after 15, 30 or 45 days of treatment. The results indicate that the gluconeogenesis was significantly inhibited in both CCl4+ethanol groups and CCl4+ethanol+colchicine groups. By contrast, the lactacidaemia levels were much higher in the CCl4+ethanol groups than the colchicine groups. Summarising, we have documented that hyperlactacidaemia is due to the inhibition of lactate utilization by the isolated hepatocytes in experimental cirrhosis, and that the improvement in lactacidaemia caused by colchicine is not primarily due to an increase in hepatic lactate utilization.
Subject(s)
Alcoholic Intoxication/metabolism , Carbon Tetrachloride Poisoning/metabolism , Colchicine/pharmacology , Lactates/metabolism , Liver/drug effects , Liver/metabolism , Animals , Carbon Tetrachloride/administration & dosage , Ethanol/administration & dosage , Gluconeogenesis/drug effects , In Vitro Techniques , Lactic Acid , Liver/cytology , Liver Cirrhosis, Experimental/metabolism , Male , Rats , Rats, WistarABSTRACT
An experimental rat liver cirrhosis, by means of carbon tetrachloride and ethanol during 8 weeks, was employed to assay the effect of Nifedipine (a calcium antagonist blocker), S-Adenosylmethionine (a precursor of glutathione); singly and in combination on rat liver cirrhosis. A slight decrease of cirrhosis (N.S.) was observed with the pharmacological therapy employed singly. The combination therapy (Nifedipine+S-Adenosylmethionine) significantly inhibited liver cirrhosis (p < 0.01).
Subject(s)
Liver Cirrhosis, Experimental/drug therapy , Nifedipine/therapeutic use , S-Adenosylmethionine/therapeutic use , Animals , Drug Therapy, Combination , Male , Nifedipine/administration & dosage , Rats , Rats, Wistar , S-Adenosylmethionine/administration & dosageABSTRACT
An experimental model of toxic liver injury in rats was employed to assay the effect of Nifedipine (a calcium antagonist blocker) and S-Adenosylmethionine (a precursor of glutathione). An important decrease in both perivenular fibrosis and cirrhosis was found. Furthermore, a significant decrease in lactic acid levels was found in the group of animals treated with pharmacologic therapy, although no correlation was seen between lactic acid levels and the different degrees of perivenular fibrosis. No significant variations in ALT and AST enzymes were observed between both groups, as opposed to a significant decrease in LDH enzyme in the Nifedipine+S-Adenosylmethionine group. The results indicate an improvement in the histologic picture of the liver in rats treated by means of pharmacological association, without any change in inflammatory infiltrate and with a slight decrease in necrosis, indicating an action mechanism via creeping fibrosis (instead of a hepatitis pathway).
Subject(s)
Liver Diseases, Alcoholic/drug therapy , Liver/drug effects , Nifedipine/pharmacology , S-Adenosylmethionine/pharmacology , Animals , Carbon Tetrachloride/toxicity , Ethanol/toxicity , Fatty Liver, Alcoholic/drug therapy , Fatty Liver, Alcoholic/pathology , Hepatitis, Alcoholic/drug therapy , Hepatitis, Alcoholic/pathology , Lactates/blood , Lactic Acid , Liver/pathology , Liver Cirrhosis, Alcoholic/drug therapy , Liver Cirrhosis, Alcoholic/pathology , Liver Diseases, Alcoholic/pathology , Male , Nifedipine/therapeutic use , Rats , Rats, Inbred Strains , S-Adenosylmethionine/therapeutic useABSTRACT
The cellular ultrastructure of isolated hepatocytes and hepatic tissue in ethanol and/or carbon tetrachloride treated rats at different times. The ultrastructural modifications induced by ethanol and carbon tetrachloride, isolated administrations, are similar: Many lipidic vacuoles, several graded-injury mitochondria and R. E. R. degeneration. These effects are also induced by ethanol and carbon tetrachloride association and furthermore nuclei indentations. Some mitochondrial autophagocytosis affecting to the less electrodense hepatocytes are noted.
