Melamine-induced adrenal structural and functional alterations and the contribution of morin to the adrenal repair in Wistar rats.

Melamine is a prevalent environmental toxicant associated with well-established toxicity on several organs. The adrenal gland is a highly dynamic organ that makes it susceptible to chemicals' toxicity. The current work investigated the adrenal histo-biochemical alterations caused by melamine exposure in rats and explored whether morin has protective potential against such adrenal toxicity. The experiment utilized 32 adult male Wistar rats randomly divided into control, morin, melamine, and melamine/morin groups. Adrenal toxicity was induced by melamine (126 mg/kg/d). Morin was used in a dose of 50 mg/kg/d. All treatments were given via oral gavage for 4 weeks. The adrenal oxidative stress markers, serum corticosterone (CORT), adrenocorticotrophic hormone (ACTH), and the mRNA expression of the steroidogenic genes; StAR (Steroidogenic acute regulatory protein), P450scc (Cholesterol side-chain cleavage enzyme), and11β-HSD1 (11β-Hydroxysteroid dehydrogenase type 1) were evaluated. Also, histological and immunohistochemical examinations of the paraffin-processed adrenal sections were performed. Melamine decreased adrenal tissue superoxide dismutase (SOD) and catalase (CAT) activities, increased adrenal malondialdehyde (MDA) levels, decreased serum CORT and increased ACTH levels, and suppressed the adrenal cortical expression of genes involved in steroidogenesis. Moreover, the inducible nitric oxide synthase (iNOS) and cysteine-aspartic acid protease-3 (caspase-3) expression were upregulated as indicated by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Besides, melamine caused remarkable adrenal histopathological changes. However, morin administration greatly repaired the adrenal injury and restored the adrenal function. Morin maintained the adrenal histoarchitecture and protected against melamine-provoked adrenal toxicity by downregulating the inflammation and the adrenal apoptotic processes and relieving the oxidative stress burden.