Vitamin D3 May Ameliorate the Ketoconazole Induced Adrenal Injury: Histological and Immunohistochemical Studies on Albino Rats

Ketoconazole (KZ) is used widely for treating the superficial, systemic fungal activities and hyperandrogenemic states. Its uses are limited by its deleterious effect on histological structure and function of the adrenal cortex. This study investigates whether vitamin D3 supplement can ameliorate the morphological changes induced by KZ. Thirty four adult male albino rats were randomized into control group (Group I) which was subdivided into: control 1 (n=7) and control 2 (n=7): In control 1, rats were intraperitoneal (I.P) injected once with 1 ml of polyethylene glycol-400 for 15 consecutive days and control 2 rats were injected I.P with (1 μg/kg) of vitamin D3 for the same period. Group II (n=10): rats were I.P injected with KZ (10 mg/100 g of body weight) once daily for 15 days; Group III (n=10): rats were I.P concomitantly injected with KZ and vitamin D3 similar doses to animals in groups II and control 2 respectively. Blood samples were collected to determine plasma ACTH, corticosterone and aldosterone levels. The right adrenal specimens sections were stained with Haematoxylin & Eosin and Masson Trichrome for histological studies and treated with Bax, Ubiquitin and vitamin D receptors for immunohistochemical studies. KZ induced adrenal cortical morphological changes in forms of disturbed adrenocorticocyte cytological architecture, nuclear changes, and intracellular lipid accumulation. KZ also increased adrenal Bax and Ub but decreased the vitamin D receptors immunopositive staining expression, in addition to increased plasma ACTH as well as decreased corticosterone and aldosterone levels. These changes were ameliorated by supplementing with vitamin D3.