Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695 012, Kerala, India.
Toxicol Mech Methods. 2012 Oct;22(8):631-7. doi: 10.3109/15376516.2012.714009.
In this study, we made an effort to evaluate the possible protective actions of melatonin on cisplatin-induced oxidative damage in mice brain homogenate and genotoxic effects in human lymphocytes under in vitro conditions. The tissue homogenate was divided into three parts. The first portion was kept as control treated with dimethyl sulphoxide (DMSO) (group 1) while the second and third portion were treated with 24 µg/g tissue cisplatin alone (group 2) and 24 µg/g tissue cisplatin in combination with 3 mM melatonin (group 3), respectively. We measured the oxidative stress biomarkers such as lipid peroxidation, 8-hydroxy 2' deoxyguanosine (8-OHdG) and antioxidant parameters such as reduced glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase in brain homogenate. Likewise peripheral venous blood was collected from healthy donors and human lymphocyte culture was done using karyotyping medium. Cultures were divided into three groups. Group 1 was the control i.e. lymphocytes treated with DMSO 5 µg/mL. In group 2, lymphocytes were treated with 2 µg/mL cisplatin and group 3 with a combination of 2 µg/mL cisplatin and 0.3 mM melatonin. Incubation of tissue homogenates with cisplatin elevated the malondialdehyde and 8-OHdG levels which were then reversed by melatonin. Reduction in antioxidant parameters with respect to corresponding controls were also restored by melatonin treatment. Furthermore, supplementation of melatonin was found to modulate the chromosome damage elicited by cisplatin which was determined using Giemsa (GTG) banding and karyotyping. These findings suggest that melatonin improves the cellular function and helps them to survive in the belligerent environment created by free radicals.
在这项研究中,我们努力评估褪黑素对顺铂诱导的小鼠脑匀浆氧化损伤和体外条件下人淋巴细胞遗传毒性的可能保护作用。组织匀浆分为三部分。第一部分作为对照,用二甲基亚砜(DMSO)处理(第 1 组),而第二和第三部分分别用 24μg/g 组织顺铂单独处理(第 2 组)和 24μg/g 组织顺铂联合 3mM 褪黑素处理(第 3 组)。我们测量了氧化应激生物标志物,如脂质过氧化、8-羟基 2'脱氧鸟苷(8-OHdG)和抗氧化参数,如还原型谷胱甘肽、超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶在脑匀浆中。同样,从健康供体采集外周静脉血,并使用染色体组型培养基进行人淋巴细胞培养。培养物分为三组。第 1 组为对照,即用 5μg/mL DMSO 处理的淋巴细胞。第 2 组用 2μg/mL 顺铂处理,第 3 组用 2μg/mL 顺铂和 0.3mM 褪黑素联合处理。组织匀浆与顺铂孵育后,丙二醛和 8-OHdG 水平升高,然后被褪黑素逆转。与相应对照相比,抗氧化参数的减少也被褪黑素处理所恢复。此外,褪黑素的补充被发现可以调节顺铂引起的染色体损伤,这是通过使用吉姆萨(GTG)带型和染色体组型来确定的。这些发现表明,褪黑素改善了细胞功能,帮助它们在自由基产生的敌对环境中存活。