Toxicological study of pyridoxal isonicotinoyl hydrazone: acute and subchronic toxicity.
Pyridoxal isonicotinoyl hydrazone (PIH) is a highly effective iron chelator. Acute toxicity testing was performed in mice and rats of both sexes, with 10 mice or rats/sex/group. The LD50 values of PIH in both species were 5 and 1 g/kg given orally and intraperitoneally, respectively. Microscopic examination of tissues from the highest oral dose (6 g/kg) animals that survived 7 days revealed fatty degeneration in the liver. Subchronic toxicity was tested in rats of both sexes, with 8 males and 8 females/group. PIH doses of 100, 400 and 800 mg/kg were given orally for 90 consecutive days. Water was given to the control group. Hematocrit and blood chemistries were analysed at weeks 3, 6, 10 and 13. There were no changes in hematocrit and BUN. PIH at doses of 800 mg/kg caused a significant increase in serum alkaline phosphatase and transaminase levels at week 13. Microscopic examination showed hepatic degeneration in a dose-related fashion. Vascular congestion of the kidney and spleen was also found. No histopathological changes were detected in sections from the stomach and intestine.
Sookvanichsilp
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N
Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Nakornchai
S
S
Weerapradist
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W
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002614:Chelating Agents / Q000633:toxicity*; D005260:Female; D006400:Hematocrit; D007274:Injections, Intraperitoneal; D007538:Isoniazid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D011730:Pyridoxal / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats
D002614:Chelating Agents; D011730:Pyridoxal; C021079:pyridoxal isonicotinoyl hydrazone; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D007538:Isoniazid