Tolerance of aged Fischer 344 rats against chlordecone-amplified carbon tetrachloride toxicity.

摘要: Abstract We have investigated the effects of chlordecone 1 ( CD )+ CCl 4 combination in adult (3 months), middle aged (14 and old (24 months) male Fischer 344 (F344) rats. After a non-toxic dietary regimen (10 ppm) or normal powdered diet for 15 days, rats received single dose CCl4 (100 μl/kg, i.p., 1:4 corn oil) oil (500 μl/kg, i.p.) alone on day 16. Liver injury was assessed by plasma ALT, AST, histopathology during time course 0–96 h. tissue repair measured [ 3 H -CH3]-thymidine -T) incorporation into hepatic nuclear DNA proliferating cell antigen (PCNA) immunohistochemistry. Hepatomicrosomal CYP2E1 protein, enzyme activity, covalent binding 14 -derived radiolabel were fed Exposure to caused modest liver only 14- 24-month-old but neither progression nor mortality. The CD+CCl4 led 100% mortality 3-month-old 72 h, whereas none died. Both 3- 14-month-old exposed had identical up 36 h indicating that bioactivation-mediated same two age groups. Thereafter, escalated while it declined In initial at 6 h similar thereafter did not develop level other groups, recovering from 96 h as Neither hepatomicrosomal protein associated p-nitrophenol hydroxylase activity differed between groups regimens 2 h after administration . Compensatory -T, PCNA) prompt robust soon stark contrast, failed allowing unabated injury. These findings suggest stimulation early onset rescue F344 lethal effect combination.