Breljak Davorka, Micek Vedran, Gerić Marko, Gajski Goran, Oguić Saša Kralik, Rašić Dubravka, Karaica Dean, Madunić Ivana Vrhovac, Ljubojević Marija, Orct Tatjana, Jurasović Jasna, Jovanović Ivana Novak, Peraica Maja, Nanić Lucia, Rubelj Ivica, Sabolić Ivan
Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.
Laboratory Animals Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.
Mutat Res Genet Toxicol Environ Mutagen. 2022 Apr-May;876-877:503443. doi: 10.1016/j.mrgentox.2022.503443. Epub 2022 Jan 12.
Aging-related impaired body structure and functions may be, at least partially, caused by elevated oxidative stress. Melatonin (MEL) and resveratrol (RSV) may act as antioxidant and anti-aging compounds, but these actions in experimental animals and humans are controversial. Herein, a rat model of aging was used to study the long-term sex-related effects of MEL and RSV treatment on body mass and blood/plasma parameters of DNA damage, oxidative status (glutathione and malondialdehyde levels), and concentrations of sex hormones. Starting from the age of 3mo, for the next 9mo or 21mo male and female Wistar rats (n = 4-7 per group) were given water to drink (controls) or 0.1 % ethanol in water (vehicle), or MEL or RSV (each 10 mg/L vehicle). DNA damage in whole blood cells was tested by comet assay, whereas in plasma, glutathione, malondialdehyde, and sex hormones were determined by established methods. Using statistical analysis of data by ANOVA/Scheffe post hoc, we observed a similar sex- and aging-dependent rise of body mass in both sexes and drop of plasma testosterone in control and vehicle-treated male rats, whose pattern remained unaffected by MEL and RSV treatment. Compared with controls, all other parameters remained largely unchanged in aging and differently treated male and female rats. We concluded that the sex- and aging-related pattern of growth and various blood parameters in rats were not affected by the long-term treatment with MEL and RSV at the estimated daily doses (300-400 μg/kg b.m.) that exceed usual moderate consumption in humans.
与衰老相关的身体结构和功能受损可能至少部分是由氧化应激升高引起的。褪黑素（MEL）和白藜芦醇（RSV）可能作为抗氧化和抗衰老化合物起作用，但这些作用在实验动物和人类中存在争议。在此，使用大鼠衰老模型来研究MEL和RSV治疗对体重以及DNA损伤、氧化状态（谷胱甘肽和丙二醛水平）和性激素浓度的血液/血浆参数的长期性别相关影响。从3个月龄开始，在接下来的9个月或21个月里，给雄性和雌性Wistar大鼠（每组n = 4 - 7）饮用自来水（对照组）或含0.1%乙醇的水（赋形剂），或MEL或RSV（每种在赋形剂中的浓度为10 mg/L）。通过彗星试验检测全血细胞中的DNA损伤，而血浆中的谷胱甘肽、丙二醛和性激素则通过既定方法测定。通过方差分析/谢费事后检验对数据进行统计分析，我们观察到对照组和接受赋形剂处理的雄性大鼠中，两性体重均有类似的性别和衰老依赖性增加，血浆睾酮水平下降，其模式不受MEL和RSV治疗的影响。与对照组相比，衰老以及接受不同处理的雄性和雌性大鼠的所有其他参数基本保持不变。我们得出结论，在估计的每日剂量（300 - 400 μg/kg体重）下，MEL和RSV的长期治疗不会影响大鼠与性别和衰老相关的生长模式及各种血液参数，该剂量超过了人类通常的适度摄入量。
