Liver damage in rats by allylisopropylacetamide (AIA), an inducer of delta-aminolevulinic acid synthetase (ALAS).
Twentyfour hours after the intraperitoneal injection of a single dose of allylisopropylacetamide (AIA) in amounts of 100 mg/kg or more to 30-day old male Wistar rats, the livers of most of the animals showed an irregular yellow coloration and a fragile consistency. No macroscopic changes were detected following AIA doses of 25 or 50 mg/kg. Bromsulphthalein retention was not significantly increased after the administration of 25 mg/kg AIA, but distinctly enhanced after 400 mg/kg. Succinate-dehydrogenase-activity in liver homogenate was not altered after 25 mg/kg, but significantly decreased after 400 mg/kg. Ethylmorphine-N-demethylation activity was enhanced after small doses without increase of cytochrome P-450 (cyt. P-450) concentration and decreased after higher doses, accompanied by a remarkable cyt. P-450 loss. GPT activity in serum and liver was not altered after both 25 and 400 mg/kg AIA. GOT activity was slightly but significantly enhanced both in serum and liver after the high dose of 400 mg/kg. Thus in addition to the well-known cyt. P-450 destruction other signs of hepatotoxicity could be demonstrated.
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis*; D000081:Acetamides / Q000633:toxicity*; D000502:Allylisopropylacetamide / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000081:Acetamides; D000502:Allylisopropylacetamide; D003577:Cytochrome P-450 Enzyme System; D000624:5-Aminolevulinate Synthetase