The effect of chronic dilantin feeding on rat gingiva, adrenal cortex and liver : morphometric and histological study

Abstract

Diphenylhydantoin" (Dilantin51 DPH or.phenytoin) is the drug of .choice for the treatment of grand mal and psychomotor epilepsy. While its advan-.- tages in the modern therapy of epilepsy are well recognized, DPH has numerous side effects; one of these side effects is.gingival hyperplasia. Since. Kitnb~ll' s description in 1939 of. h:,-rperplastic. chaq.ges in the gingiva . . of epileptics_treated with. diphenylhydantoin51 many investigators have been ... concerned with this complication. The exact mechanism of action of DPH on the gingival tissues,is obscure due to the lack of an appropriate animal model .for the diseasee The present study demonstrates a method for the production of dilantin gingival hyperplasia in rats and its quantitation. Previous studies attempting to produce such dilantin side effect in the rat were not success-= ~ale albino rats divided into 5 groups, were housed 3/cage and fed powdered cariogenic diete Group A1 arid A2 were designated as controls for ( the 8 weeks and 14 weeks drug treated groups~ respective1yo Group B rats were fed a powdered, cariogenic diet containing 140 mg/kg DPH for 8 weekso Group· C rats were fed 140 mg/kg· DPH for 14 weeks and. group D were fed 140 mg/kg DPH for 8 weeks and 280 mg/kg DPH for:6 more weekso The animals were sacrificed by decapitationo The skulls were fixed 51 trimmed, cleaned and decalcified. The jaws were oriented in the same way" during embedding for all the control and experimental tissues so that coronal histological sections of the teeth and gingivae were consistently obtained. The sections were cut at 7 ~ and stained with H&E~ The stained coronal sections of the upper and lower jaws from both posterior and anterior regions were examined using Zeiss photomicroscope II equipped with a projection screen and an integration grid. The epithelium of the gingiva and the underlying connective tissue were the tissues studied. The image of the tissue section. was projected on the screen and the number of grid points superimposed on tne different areas of epithelium and underlying connective t·issue were counted at the same m?-gnification (80.X} for bothcontrol and experimental tissues. The data collected were the number of points oveJ;lying, the ~pi-... thelium and. connective tissueG In addition to the gingiva, the.adrenals, liver· and heart from each animal were excised at the t.ime of animai sacrir fice. . The weight of the· empty heart was recorded without further processing o The adrenals and livers were processed for histo.logical examinationo The results showed a significant increase in the absolute and relative weights of adrenals of Group D (fed higher dose of DPH). Histologically the~e was hypertrophy of cells in the Zonae Fisciculata and Reticularis in the DPH treated rats particularly those treated with the higher dose (Group D)e In the liver there was a significant increase in relative liver weights of rats from Group D when compared to control group. The histological sections showed hypertrophy of liver cells and increase in the cytoplasmic eosinophilia. The histological sections of gingiva from DPH treated rats showed an apparent ~increase in the thickness of the epithelium with elongation of the rete pegs and an increase in the thickness of ·collagen bundles, with aggregation of dense collagen fibers particularly in Group D •. The data·collected from point counting analysis was equivalent to either the relative gingival surface area or, assuming all sections have the. same thickness, the relative gingival volume. The upper poste.rior buccal,. lower posterior buccal, upper posterior palatal and lower posterior lingual gingiva fro1n Group D showed a significant increase in the total relative gin~ gival surface area and in the relative area of both epithelium and connective ti.ssue when compared to their respective control values. In conclusion these data showll for the first time, that.the rat gingiva responds to chronic treatment of dilantin similar to human gingiva,. even tho~gh the magnitude of the change is not ·large enough· to· make the hyperplasia clinically obviohs in the rat, as· seen in the.humano . . . . . . . Also,. DPH caused adrenal· hypertrophy, but the.role of this change: i.D. the · pathogenesis of gingival hyperplasia is not known and needs further investigation.