Jain Anshu, Agrawal Shruti, Flora Swaran J S
Division of Regulatory Toxicology, Defence Research and Development Establishment, Gwalior 474 002, Madhya Pradesh, India.
Toxicol Rep. 2015 Sep 28;2:1334-1346. doi: 10.1016/j.toxrep.2015.09.003. eCollection 2015.
Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water) or nicotine (0.25 mg/kg, sub-cutaneously) for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH) were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism) in male rats.
砷和尼古丁暴露一直是全球主要的健康问题。单独来看,这两种毒物都会增加患包括癌症在内的各种疾病的风险。然而,关于共同暴露的信息有限。在本研究中,我们评估了它们单独暴露和联合暴露的影响,以及这两种毒物的共同暴露是否可能产生协同作用或拮抗作用。雄性大鼠暴露于极低剂量的砷(饮用水中25 ppm)或尼古丁(0.25 mg/kg,皮下注射)5个月,暴露后评估各种指示氧化应激和细胞凋亡的生化变量。几乎所有与谷胱甘肽相关的酶在单独暴露组和共同暴露组中均表现出明显变化。虽然血清肌酐和细胞凋亡指标乳酸脱氢酶(LDH)在两种处理中均显著升高,但在共同暴露组中观察到了相加效应。在脑和肝脏中也观察到了类似趋势,但在肾脏中未观察到。基因表达研究表明,过氧化氢酶、铜锌超氧化物歧化酶、谷胱甘肽S-转移酶显著降低,各种组织中的Bax、半胱天冬酶3以及尿8-羟基脱氧鸟苷水平显著上调,表明存在DNA损伤和细胞凋亡。有趣的是,与单独暴露于砷的组相比,共同暴露组的肝脏砷浓度有所下降。总之,本研究表明,砷和尼古丁在单独暴露时表现出显著毒性,而在雄性大鼠中,这两种毒素的共同暴露表现出不同情况(指示协同作用和拮抗作用)。