Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats
Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats
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DOI：
10.1046/j.1440-1681.1999.03157.x
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发表时间：
1999-11-01
影响因子：
2.9
通讯作者：
Flora, SJS
中科院分区：
文献类型：
--
作者：
Flora, SJS
1、本研究通过对几个指标的研究，探讨了砷对大鼠肝、脑和红细胞氧化应激的影响。它还探讨了联合施用N '-乙酰半胱氨酸（NAC）和内消旋2，3-二巯基琥珀酸（DMSA）能够在指示砷诱导的氧化应激的参数中实现比单独使用这些药物中的任一种更好的可逆性的可能性，2。雄性大鼠暴露于100 p，p.m，亚砷酸钠在他们的饮用水12周（相当于12毫克/公斤砷）。然后去除砷，并给予大鼠NAC（1 mmol/kg/天），DMSA（1 mmol/kg/天）或两者的组合，口服，每天一次，持续5天。未给予砷的动物和给予砷但不给予NAC或DR伊萨的动物分别作为阴性和阳性对照。3.发现12周的砷暴露使肝和脑样品中的谷胱甘肽（GSH）水平降低，氧化型谷胱甘肽（GSSG）增加，并促进丙二醛（MDA）的产生。除了红细胞δ-氨基乙酰丙酸脱氢酶（ALAD）活性和GSH水平显著降低外，MDA产生的显著升高也可能有助于砷诱导的氧化应激。单独用NAC或DMSA治疗可部分逆转砷诱导的肝GSH和R-IDA的改变，而只有脑MDA水平对这些药物有利。只有DMSA似乎恢复血ALAD，而RBC MDA水平对这两种药物都有利。用DMSA治疗也能有效地降低血液和肝脏中的砷浓度。在肝脏中，与任一药物单独的作用相比，NAC和DMSA的组合治疗更有效地逆转了这些参数中的大多数。5。这些结果提供了砷诱导的肝脏、脑和RBC中的氧化应激的体内证据，并表明这些作用可以通过包括NAC和DR-ISA的组合治疗的药理学干预来减轻。
1, The present study examined whether arsenic induces oxidative stress in liver, brain and erythrocytes (RBC) based on the investigation of certain selected parameters. It also explored the possibility that combined administration of N'-acetylcysteine (NAC) and meso 2,3-dimercaptosuccinic acid (DMSA) was capable of achieving better reversibility in the parameters indicative of arsenic-induced oxidative stress than individual treatment with either of these drugs,2. Male rats were exposed to 100 p,p.m, sodium arsenite in their drinking water for 12 weeks (equivalent to 12 mg/kg As). The arsenic was then removed and rats were given NAC (1 mmol/kg per day), DMSA (1 mmol/kg per day) or a combination of the two, orally, once daily for 5 days. Animals not given arsenic and those given arsenic hut not NAC or DR ISA served as negative and positive controls, respectively,3, Twelve weeks of arsenic exposure was found to deplete glutathione (GSH) levels, increase oxidized glutathione (GSSG) and promote malondialdehyde (MDA) production in both liver and brain samples. In addition to a significant reduction in RBC delta-aminolevulinic acid dehydratase (ALAD) activity and GSH levels, a marked elevation in MDA production may also contribute to arsenic-induced oxidative stress. it,4 Treatment with either NAC or DMSA alone partially reversed arsenic-induced alterations in hepatic GSH and R-IDA, while only brain MDA levels responded favourably to these drags, Only DMSA appeared to restore blood ALAD, while RBC MDA levels responded favourably to both drugs. Treatment with DMSA also produced an effective depletion of blood and hepatic arsenic concentrations. In the liver, most of these parameters were more effectively reversed by combined treatment with NAC and DMSA compared with the effects of either drug alone,5, These results pro vide irt vivo evidence of arsenic-induced oxidative stress in li cer, brain and RBC and indicate that these effects can be mitigated by pharmacological intervention that encompasses combined treatment with NAC and DR-ISA.