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Cigarette smoking is harmful to the health of both smokers and nonsmokers. It is a major cause of death. This study aimed to investigate the structural changes in the zona fasciculata of albino rats caused by nicotine and the protective effect of grape seeds with or without the stoppage of nicotine administration. Thirty-five adult male rats were used and equally divided into five groups: negative and positive control groups (Groups I and II), nicotine-treated group (Group III), nicotine- and grape seed extract-treated group (Group IV), and nicotine withdrawal and grape seed extract-treated group (Group V). Adrenal glands were dissected and prepared for histological studies. The majority of zona fasciculata cells of Group III showed striking changes in terms of swelling of the cells with marked cytoplasmic vacuolation, many pyknotic nuclei, and increased immunoexpression to caspase 3 antibodies. By electron microscopy, a marked increase in lipid deposition with its appearance in the capillary between zona fasciculata cells was noticed. Heterochromatic nuclei and dilated smooth endoplasmic reticulum were noted. Degenerated mitochondria and some mitochondria that had cavitation with a progressive loss of their cristae were seen. The zona fasciculata cells of Group IV were partially improved, while in Group V, those cells showed complete improvement. We can conclude that nicotine causes severe histological changes in zona fasciculata cells. Grape seed extract can partially ameliorate these changes, and complete recovery is achieved with grape seed extract after the stoppage of nicotine administration.

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