Myricetin attenuates atrazine-induced dysregulation of the hypothalamic-pituitary-adrenal axis of rats via anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms

The hypothalamic-pituitary-adrenal (HPA) axis is an important part of the stress response system that produces a biological reaction to stressful stimuli and can be activated by stressors such as atrazine. Atrazine (ATZ) is a common triazine herbicide used in the management of weeds in corn and sugarcane, and its persistence in the environment through runoff and leaching leads to frequent contamination of soil and water, with subsequent adverse health implications. Myricetin (MYR) is a biologically active compound with various pharmacological potentials against noxious agents. This study evaluated the effects of MYR on the HPA axis of male Wistar rats sub-chronically exposed to atrazine (ATZ), gavaged with either atrazine (50 mg/kg), myricetin (20 mg/kg), or a combination of both for 45 consecutive days. Exposure to ATZ increased serum levels of adrenocorticotropin-releasing hormone (ACTH) and corticosterone, and significantly decreased the activities of hypothalamic and adrenal antioxidant enzymes (catalase, glutathione S-transferase, glutathione peroxidase, reduced glutathione), and hypothalamic acetylcholinesterase (AChE). More so, ATZ-challenged rats showed increased levels of reactive oxygen species and lipid peroxidation, Nitric oxide, tumor necrosis factor-α, interleukin-1β, and caspase-3 in both tissues. Conversely, treatment with myricetin significantly restored the serum levels of ACTH and corticosterone, enhanced the antioxidant enzyme activities, reduced the oxidative-inflammatory and apoptotic markers in both tissues, and increased the hypothalamic AChE activity of the treated animals. Myricetin also reversed the histological abnormalities that atrazine elicited in the treated animals. Overall, MYR, through its antioxidant, anti-inflammatory, and anti-apoptotic properties, attenuated the ATZ-induced disruption of the HPA axis of rats.