[Oral administration of diphenylhydantoin sodium (DFH-Na or phenytoin) predictably affects the liver and kidney of Sprague Dawley rats]. / La administración oral de difenilhidantoinato sódico (DFH-Na ó Fenitoina) afecta previsiblemente hígado y riñón de ratas Sprague-Dawley.

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.

[Modified procedure for screening anticonvulsants. Re-evaluation of sodium diphenylhydantoin and phenobarbital]. / Procedimiento modificado para tamizaje anticonvulsionante. Reevalucación del difenilhidantoinato sódico y el fenobarbital.

A modified antiepileptic screening procedure to test anticonvulsant drugs is shown. Diphenylhydantoin sodium salt (DFH-Na) and phenobarbital (Phb) were tested throughout 8 h, at hourly intervals after a single oral drug intake in rats. Another group was tested at steady stage of DFH-Na during 7 days period. A single dose of DFH-Na was orally administrated to male and female rats (30 mg/kg) and after testing throughout 8 h: 0, 5, 28, 38, 52, 70 and 75% and 10, 18, 50, 35, 62, 50 and 70% protection against MES, was found. Only 20% protection was found in females to METsc test on the 6th and 7th h. However, 80, 60, 60 and 20% males were found protected against METsc test from the 4th to the 8th hour. Maximum blood serum levels were 2 micrograms/ml. Phenobarbital at doses 12 mg/kg in males and females as well showed: 30, 64, 66, 74, 84, 90, 40, 34% and 14, 36, 53, 41, 55, 70, 82 and 82% protection against MES, respectively. On the other hand, 60, 60, 46, 47, 94, 100, 80 and 20% and 80, 80, 46, 70, 60, 40, 80 and 20% of males and females were protected against METsc test, respectively. An average of 8 micrograms/ml and 12 micrograms/ml of Phb serum levels were found since the 1 to the 8th and 5th hours, correspondingly. A 28% protection of both male and female rats to MES test was found following 7 days of treatment with DFH-Na (30 mg/kg) treatment. Also an average of 10% female and males were found protected against METsc test.

Progesterone fate in rabbit cornea.

Excised cornea from adult New Zealand rabbits were incubated with progesterone-4-14C in Eagle's media for 96 hr. Samples were inactivated at intervals of 24 hr incubation periods. The following metabolites of progesterone were isolated: 20 alpha-Hydroxy-4-pregnen-3-one, 20-hydroxy-4-pregnen-3-one, 5 alpha-pregnane-3,20-dione; 5 beta-pregnane-3,20-dione and 6 beta-hydroxy-4-pregnen-3,20-dione. 20 alpha-Hydroxy-pregnen-3-one was the predominant metabolite of progesterone-4-14C. A linear increase was observed throughout 96 hr. The opposite was found for 5 alpha and 5 beta pregnane-3,20-dione. Compounds remaining at the origin of the paper chromatograms contained 6 beta-hydroxy-4-pregnen-3,20-dione and other still unidentified metabolites of progesterone-4-14C. Presence of 20 alpha and 20 beta-reductase; 5 alpha and 5 beta-reductase and 6 beta-hydroxylase enzyme systems are involved in corneal progesterone metabolism. No fungal neither bacterial enzymatic biotransformation occurred in the culture media.

Iron binding to nutrients containing fiber and phenytoin.

Ascorbate and citrate extracted more iron than EDTA from pig foodstuffs (P less than 0.001). Glucose-saline solution (GSS) and ascorbate were less capable than citrate of extracting iron from maize tortilla (P less than 0.001). GSS extracted 16-32% of the whole iron contained in the studied foodstuffs; 30, 40 and 42% of the remaining iron in maize bran, wheat bran and pig feed was released with 0.1 M HCl. 40% of the remaining iron in pig's feed was released with 5% pepsin-0.1 M HCl while the iron of cereals required an additional extraction with 1% ascorbate. 5% pepsin-0.1 M HCl solutions released more iron as the protein content in the foodstuffs increased (P less than 0.001). Iron-extracted maize fibers (Ftw/Fe) bound significantly more iron than Ftc/Fe, FDA and FDN correspondingly (P less than 0.001). Phenytoin bound significantly more iron than total maize fibers both, with and without previous iron extraction (P less than 0.001). Also, phenytoin combined with maize-fiber bound less iron than phenytoin alone in G.S.A.

Valproic acid and phenytoin effects on serum proteins and immunoglobulins of epileptic patients.

An evaluation of serum protein and immunoglobulins with regard to valproic acid (VPA) and phenytoin (phen) serum levels was performed in 28 epileptic patients. Serum antiepileptic levels were measured in fasting conditions. All patients were classified into the following groups: A (VPA below 50 micrograms/ml), B (VPA 50-89 micrograms/ml), C (VPA above 89 micrograms/ml), D (VPA 50-89 micrograms/ml and phen below 10 micrograms/ml). Patients of group C showed higher serum protein values than groups A (P less than 0.02), B and D (P less than 0.001). The alpha 2 and beta-globulin fractions were higher in group C than the remaining groups (P less than 0.05). Immunoglobulin A, G and M remained unaltered in all patients.

Response of rats to seizure stimulus modified by feeding.

Wistar (W) and Sprague-Dawley (S.D.) rats responded differently to electroshock and metrazole test when fed with two diets (A and B). Latency periods of B for male (m) and female (f) were: W.m. greater than W.f. (P less than 0.001); W.m. greater than S.D.m. (P less than 0.05); S.D.f. greater than W.m. (P less than 0.001); S.D.m. B greater than S.D.m. A (P less than 0.001); W.m. B greater than W and S.D.m. A (P less than 0.001). Preconvulsive period for B were: W.f. and m. greater than S.D.f. and m. (P less than 0.001); W.m. greater than S.D.m. (P less than 0.001); W.m. greater than S.D.f. (P less than 0.001); S.D.m. greater than S.D.f. (P less than 0.001) and W.m. greater than W.f. (P less than 0.001). Effects of A were negligible. Phenytoin and phenobarbital protected against electroshock.