Astaxanthin alleviates fipronil-induced neuronal damages in male rats through modulating oxidative stress, apoptosis, and inflammatory markers

Abstract

Abstract Fipronil (FPN) is an effective pesticide for veterinary and agricultural use; however, it can induce neurotoxic effects on non-target organisms after accidental exposure. Astaxanthin (AST) is a dark red carotenoid with antioxidant, anti-inflammatory, neuroprotective, and antiapoptotic effects. This study investigated the ameliorative impact of AST against FPN-induced brain damage in rats. Thirty-two adult Wistar rats were allocated into four groups (n = 8): Control, AST (20 mg/kg bwt/day), fipronil (FPN) (20 mg/kg bwt/day), and AST + FPN group. Acetylcholine (ACh), dopamine, malondialdehyde (MDA), and proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and inflammatory cytokine cyclooxygenase-2 (COX2) levels were enhanced in the FPN-administered group relative to the control group. In addition, a substantial reduction of acetylcholine esterase (AchE), gamma-aminobutyric acid (GABA), serotonin, reduced glutathione (GSH) levels, catalase (CAT), and total superoxide dismutase (T-SOD) enzyme activities were determined. FPN induced histopathological alterations in the cerebral and cerebellar tissues. Likewise, the histomorphometric image analysis of H and E-stained tissue sections was constant with FPN-induced neurotoxicity. Immunohistochemically, an intense positive immunohistochemical staining of apoptotic marker caspase-3 and astrocytes activation marker glial fibrillary acidic protein (GFAP) in the examined tissues was noticed. Inversely, the simultaneous administration of AST partially attenuated FPN impacts, ameliorating the severity of FPN-induced neuronal damage. These results were also established with the molecular docking findings. It could be suggested that AST has antioxidant, anti-inflammatory, and anti-apoptotic capabilities against FPN-induced neuronal damage via suppression of oxidative stress and pro-inflammatory cytokines, preservation of the neurotransmitters, and the cerebral and cerebellar histoarchitectures.