The protective role of l-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats

Heba-Tallah Abd Elrahim Abd Elkader, Marium Marzoq Hussein, Nema A . Mohammed, Heba M . Abdou
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Abstract

Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential. l-Carnitine (LC) is regarded as the “gatekeeper” in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity.

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左旋肉碱对噻虫嗪诱导的雄性大鼠大脑氧化应激、神经递质紊乱、星形胶质细胞增生和细胞凋亡的保护作用
除虫菊酯、有机磷、新烟碱等合成有机杀虫剂有可能破坏生态系统,而且通常对人类有毒。噻虫嗪(TMX)是一种新烟碱类杀虫剂,是一种广泛使用的具有潜在神经毒性的杀虫剂。左旋肉碱是一种内源性化学物质,除了在能量代谢中发挥作用外,还以其潜在的生物活性而闻名。本研究调查了 LC 对雄性 Wistar 大鼠 TMX 引起的神经毒性的保护作用。动物被分为四组,每天分别接受 LC(300 毫克/千克)、TMX(100 毫克/千克)或上述两种剂量的治疗,为期 28 天。我们的研究结果表明,TMX 处理的大鼠血清脂质和电解质发生明显变化,大脑抗氧化剂和神经递质(乙酰胆碱、多巴胺和血清素水平)下降,硫代巴比妥酸活性物质和促炎细胞因子水平升高,乙酰胆碱酯酶和单胺氧化酶的大脑活性也升高。TMX 还增加了 Caspase-3 和神经胶质纤维酸性蛋白的表达。相比之下,使用 LC 进行预处理可抑制氧化应激和促炎细胞因子,并调节神经递质水平,从而减轻 TMX 引起的脑损伤。它还能改善凋亡和星形胶质细胞标志物的表达。由此可以得出结论,LC 对 TMX 神经毒性具有抗氧化、抗炎、抗星形胶质细胞增生和抗凋亡的潜力。
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