多氯联苯(PCB)是潜在的有害环境毒物,可导致具有抑郁特征的认知功能下降。PCB诱导的行为缺陷与神经化学功能障碍有关,免疫变化,和氧化应激。这项研究调查了D-核糖-L-半胱氨酸(DRLC)的神经保护作用,谷胱甘肽的神经保护性前体元素对PCB诱导的神经行为障碍。在最初15天的PCB(2mg/kg)暴露于大鼠之后,DRLC(50mg/kg)再口服15天,从第16天到第30天。评估动物的行为效应,如运动的变化,认知,和抑郁症。氧化/硝能应激标记;抗氧化调节蛋白对氧磷酶-1(PON-1),血红素加氧酶-1(HO-1),核因子红系2相关因子2(Nfr2),NADPH氧化酶-1(NOX-1),NAD(P)H醌氧化还原酶1(NQO1),和神经炎症(NF-kβ,和TNF-α);和神经化学代谢酶(乙酰胆碱酯酶(AChE),单胺氧化酶-A和-B(MAO-A,MAO-B))进行。PCB引起的运动能力下降,认知表现,DRLC逆转了抑郁样特征。更具体地说,PCB诱导的氧化和硝态应激,以降低水平的GSH为代表,CAT,和SOD,伴随着升高的MDA和亚硝酸盐被DRLC减毒。此外,DRLC将NF-kβ和TNF-α水平降低所指示的神经炎性环境恢复至正常。AChE的过度活动,MAO-A,MAO-B,DLRC减轻了由于PCB暴露引起的PON-1和NOX-1水平以及Nfr2,NQO1和PON-1。我们的结果表明,DRLC作为一种前瞻性的神经治疗剂,可以通过抗氧化和抗硝能应激来对抗PCB诱导的神经行为障碍,例如认知缺陷和抑郁样特征,抗神经炎症,抑制大脑代谢酶,和神经化学稳态正常化。
Polychlorinated biphenyl (PCB) is potentially harmful environmental toxicant causing cognitive decline with depressive features. PCB-induced behavioral deficits are associated with neurochemical dysfunctions, immune changes, and oxidative stress. This study investigated the neuroprotective effects of D-ribose-L-cysteine (DRLC), a neuroprotective precursor element of glutathione on PCB-induced neurobehavioral impairments. Following the initial 15 days of PCB (2 mg/kg) exposure to rats, DRLC (50 mg/kg) was given orally for an additional 15 days, from days 16 to 30. Animals were assessed for behavioral effect such as changes in locomotion, cognition, and depression. Oxidative/nitrergic stress markers; antioxidant regulatory proteins paraoxonase-1 (PON-1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nfr2), NADPH oxidase-1 (NOX-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and neuroinflammation (NF-kβ, and TNF-α); and neurochemical metabolizing enzymes (acetylcholinesterase (AChE), monoamine oxidase-A and -B (MAO-A, MAO-B)) were carried out. The PCB-induced decline in locomotion, cognitive performance, and depressive-like features were reversed by DRLC. More specifically, PCB-induced oxidative and nitrergic stress, typified by reduced levels GSH, CAT, and SOD, accompanied by elevated MDA and nitrite were attenuated by DRLC. Additionally, DRLC restored the neuroinflammatory milieu indicated by decreased NF-kβ and TNF-α levels toward normal. Hyperactivities of AChE, MAO-A, MAO-B, PON-1, and NOX-1 levels as well as Nfr2, NQO1, and PON-1 due to PCB exposure were mitigated by DLRC. Our results suggest DRLC as a prospective neurotherapeutic agent against PCB-induced neurobehavioral impairments such as cognitive deficit and depressive-like feature through antioxidative and anti-nitrergic stress, anti-neuroinflammation, inhibition of brain metabolizing enzymes, and normalization of neurochemical homeostasis.