[Oral administration of diphenylhydantoin sodium (DFH-Na or phenytoin) predictably affects the liver and kidney of Sprague Dawley rats].
Phenytoin and its vehicle were orally administered to adult Sprague-Dawley rats during 7, 14 and 30 days at doses of 300 and 450 mg/kg/24 hr., respectively. We found: 1) Increased liver DNA concentration in subgroups of animals treated with 450 mg at 7 (P < 0.02) and 15 days (P < 0.001) Phenytoin serum levels were 19 ug/ml. 2) Increased protein concentration with 300 mg at 7 (P < 0.01) and 15 days (P < 0.001), respectively. 3) Cloudy swelling, vacuolar degeneration, liver sinusoids disappearance and lymphocytic cells infiltrate in subgroups of rats receiving vehicle throughout 6, 14 and 15 days correspondingly. The former lesion was found in all subgroups, except that 450 mg treated animals liver more severely affected. 4) Increased DNA concentration in kidney of subgroups receiving 450 mg/kg throughout 7 (P < 0.05), 15 (P < 0.001) and 30 days (P < 0.001), correspondingly. 5) Increased protein concentration in rats receiving 450 mg during 15 days (P < 0.001) and severely decreased at 30 days period. 6) Cloudy swelling was found in all treated animals subgroups. Seven cellular and tissue lesions were caused by vehicle at 15 and 30 days periods. 450 mg of phenytoin predominantly caused tissue condensation and vacuolar degeneration in kidney cortex. 7) propylene glycol do affect liver and kidney at doses below TD-50. Phenytoin stimulate kidney and liver cell proliferation. Caution should be observed when using parenteral phenytoin.
Garzón de la Mora
P
P
División de Bioquímica-Farmacológica, Unidad de Inv. Biomédicas de Occidente C.M.O. IMSS, Guadalajara, Jalisco, México.
García-Estrada
J
J
Navarro-Ruíz
A
A
Román-Maldonado
S
S
Bastidas-Ramírez
B E
BE
González-Hita
M
M
Navarro-Ruiz
I
I
D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000633:toxicity; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D011409:Propylene Glycols; D010672:Phenytoin; D019946:Propylene Glycol; D004247:DNA
La administración oral de difenilhidantoinato sódico (DFH-Na ó Fenitoina) afecta previsiblemente hígado y riñón de ratas Sprague-Dawley.