Four-week oral toxicity study of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in uremic rats.
A short-term oral toxicity study of 1,2-dimethyl-3-hydroxypyrid-4-one (L1), a promising oral chelating agent for the treatment of iron and aluminum overload, was carried out in uremic rats. L1 was administered to male uremic rats by gastric intubation at 0, 20, 40, 80 or 160 mg/kg/d for 4 w. Body weight and food and fluid intake were monitored daily. Complete hematologic examinations, serum biochemical parameter determinations and histological examinations were carried out. Although body weight gain was significantly reduced at 80 and 160 mg/kg/d, there were no effects of L1 on food and fluid consumption. There were no significant differences between controls and L1-treated groups in most of the hematological and biochemical parameters analyzed. No significant dose-dependent changes in relative organ weights were noted. The non-observed-adverse-effect level (NOAEL) for L1 in uremic rats was 40 mg/kg/d. According to the results of this study, uremia did not increase the toxic effects of L1.
Laboratory of Toxicology and Biochemistry, School of Medicine, Rovira i Virgili University, Reus, Spain.
M
M
Gomez
J L
JL
Domingo
D
D
del Castillo
J M
JM
Llobet
J
J
Corbella
D000284:Administration, Oral; D000535:Aluminum / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D000077543:Deferiprone; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011728:Pyridones / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects; D013737:Testis / Q000187:drug effects; D014511:Uremia / Q000188:drug therapy* / Q000503:physiopathology
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D000535:Aluminum; D007501:Iron