INFLUENCE OF MELATONIN AND ITS AGONIST ON HISTOPATHOLOGICAL CHANGES OF THYROID, SPLEEN AND ADRENAL GLANDS IN FUNCTIONAL AND STRUCTURAL PINEALECTOMIZED RATS

Abstract

The pineal gland, through its secretion of melatonin, plays a central role in regulating circadian rhythms, oxidative balance, and immune-endocrine homeostasis. Disruption of pineal activity by continuous light exposure or surgical pinealectomy has been shown to induce oxidative stress, tissue degeneration, and immune dysregulation in peripheral organs. The present study investigated the histopathological and immunohistochemical changes in the thyroid gland, adrenal glands, and spleen of adult male albino rats following pinealectomy and continuous light exposure, and further evaluated the protective effects of melatonin and its receptor agonist, ramelteon. Seventy rats were divided into control, pinealectomy, continuous light, melatonin-treated, and ramelteon-treated groups and maintained under standard laboratory conditions for a 10-week experimental period. Histological examination revealed that both continuous light and pinealectomy induced profound architectural alterations, including follicular disorganization and colloid depletion in the thyroid, cortical vacuolation and chromaffin cell damage in the adrenal glands, and necrosis, congestion, and hemorrhage in the spleen. These changes were accompanied by marked increases in CD163-positive macrophage expression, indicating enhanced inflammatory and immune responses. Treatment with melatonin partially preserved tissue integrity by maintaining follicular and cortical structures and reducing immune cell infiltration. Notably, ramelteon demonstrated comparable, and in some cases stronger, protective effects, restoring near-normal histological features in adrenal and splenic tissues and suppressing CD163 immunoreactivity to lower levels. Together, these findings highlight the essential role of pineal-derived melatonin in maintaining circadian rhythm–dependent endocrine and immune functions. Moreover, they emphasize the therapeutic potential of melatonin receptor agonists such as ramelteon as clinical alternatives in conditions associated with circadian disruption, oxidative injury, and immune imbalance.