Cytogenetics and Molecular Toxicology Laboratory, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh, Uttar Pradesh, 202002, India.
Mol Biol Rep. 2021 Apr;48(4):3367-3377. doi: 10.1007/s11033-021-06394-x. Epub 2021 May 19.
TiO NPs have been investigated for their toxic potential and studies have reported their toxicity is due to generation of oxidative stress. In the present study, we investigated the toxicity of TiO NPs and explored the potential of well-known antioxidant coenzyme Q10 (CoQ10) in counteracting the NP-induced toxicity in isolated human blood cells. When the isolated blood cells were treated with varying concentrations of TiO NPs (25-100 μg/ml), only 50 μg/ml dose induced statistically significant hemolysis in erythrocytes and cytotoxicity in lymphocytes (p < 0.05). None of the concentrations induced any significant increase in platelet aggregation. To investigate the protective effect of CoQ10, we incubated the isolated blood cells with 50 μg/ml of TiO NPs in the presence and absence of 25 μM of CoQ10 for 3 h. Hemolysis, oxidative stress, LDH leakage and ATPase enzyme activity were studied in erythrocytes; cytotoxic and DNA damaging potential of NPs were determined in lymphocytes, along with mitochondrial membrane potential (MMP) and ADP/ATP ratio. Hemolysis, generation of oxidative stress, LDH leakage and reduced ATPase activity were observed in the erythrocytes treated with NPs alone (50 μg/ml), the results were statistically significant at p < 0.05. Oxidative stress was evident by increased levels of malonaldehyde, indicating lipid peroxidation and generation of reactive oxygen species including hydrogen peroxide, together with statistically significant decrease in the activities of catalase and superoxide dismutase and reduced glutathione levels. In the lymphocytes treated with NPs alone (50 μg/ml), cytotoxicity in MTT assay and DNA damage in comet assay were observed; in addition, mitochondrial membrane potential collapsed and ADP/ATP ratio increased indicating mitochondrial function impairment. However, in the presence of CoQ10, hemolysis, oxidative stress and LDH leakage in the erythrocytes and lymphocyte cytotoxicity and DNA damage were drastically reduced, enzyme activities, MMP and ADP/ATP ratio were restored towards normal levels. TiO NPs induce cytotoxicity, damage DNA in lymphocytes, and induce oxidative/anti-oxidative imbalance in erythrocytes. Antioxidant CoQ10 protects erythrocytes and lymphocytes from toxicity induced by TiO NPs.
TiO NPs 已被研究其潜在毒性，研究报告称其毒性是由于氧化应激的产生。在本研究中，我们研究了 TiO NPs 的毒性，并探索了著名抗氧化辅酶 Q10（CoQ10）在对抗 NP 诱导的人血离体细胞毒性方面的潜力。当分离的血细胞用不同浓度的 TiO NPs（25-100μg/ml）处理时，只有 50μg/ml 的剂量在红细胞中引起统计学上显著的溶血，在淋巴细胞中引起细胞毒性（p<0.05）。没有一个浓度引起血小板聚集的任何显著增加。为了研究 CoQ10 的保护作用，我们将分离的血细胞与 50μg/ml 的 TiO NPs 一起孵育，在存在和不存在 25μM CoQ10 的情况下孵育 3 小时。研究了红细胞中的溶血、氧化应激、LDH 漏出和 ATP 酶活性；在淋巴细胞中测定了 NPs 的细胞毒性和 DNA 损伤潜力，以及线粒体膜电位（MMP）和 ADP/ATP 比。在单独用 NPs（50μg/ml）处理的红细胞中观察到溶血、氧化应激、LDH 漏出和降低的 ATP 酶活性，结果在 p<0.05 时具有统计学意义。通过增加丙二醛的水平表明脂质过氧化和活性氧的产生，包括过氧化氢，同时过氧化氢酶和超氧化物歧化酶的活性显著降低，以及还原型谷胱甘肽水平降低，氧化应激是明显的。在单独用 NPs（50μg/ml）处理的淋巴细胞中，MTT 测定中的细胞毒性和彗星试验中的 DNA 损伤被观察到；此外，线粒体膜电位崩溃，ADP/ATP 比增加，表明线粒体功能受损。然而，在 CoQ10 的存在下，红细胞中的溶血、氧化应激和 LDH 漏出以及淋巴细胞的细胞毒性和 DNA 损伤大大减少，酶活性、MMP 和 ADP/ATP 比恢复到正常水平。TiO NPs 诱导淋巴细胞的细胞毒性、DNA 损伤，并诱导红细胞中的氧化/抗氧化失衡。抗氧化辅酶 Q10 可保护红细胞和淋巴细胞免受 TiO NPs 诱导的毒性。
