Liver cell enlargement in rats given hydroxymethyl pyrroles analogous to pyrrolizidine alkaloid metabolites, followed later by the hepatotoxin dimethylnitrosamine.
Male rats aged 4-5 weeks were given single doses of pyrrolic alcohols having alkylating properties similar to those of pyrrolizidine alkaloid metabolites, followed several days later by one of the hepatotoxins dimethylnitrosamine (DMN), thioacetamide (TA) or carbon tetrachloride. After 24-32 days the livers of animals given the pyrroles 1-methyl-2,3-bishydroxymethylpyrrole (II) or 1-phenyl-5-methyl-2,3-bishydroxymethylpyrrole (V) and then DMN, contained enlarged parenchymal cells (megalocytes) similar to those seen in chronic pyrrolizidine alkaloid poisoning. At this time such abnormal cells were not found in rats given any of the other pyrroles followed by DMN, or compound II and then TA or CCl4.
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002452:Cell Count; D004128:Dimethylnitrosamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D008099:Liver / Q000166:cytology*; D008297:Male; D008938:Mitosis / Q000187:drug effects; D011758:Pyrroles / Q000633:toxicity*; D051381:Rats; D013853:Thioacetamide / Q000633:toxicity; D013997:Time Factors
D011758:Pyrroles; D013853:Thioacetamide; D002251:Carbon Tetrachloride; D004128:Dimethylnitrosamine