Rodriguez M I, Escames G, López L C, García J A, Ortiz F, López A, Acuña-Castroviejo D
Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Universidad de Granada, Avenida de Madrid 11, E-18012 Granada, Spain.
J Endocrinol. 2007 Sep;194(3):637-43. doi: 10.1677/JOE-07-0260.
Cardiac and diaphragmatic mitochondria from male SAMP8 (senescent) and SAMR1 (resistant) mice of 5 or 10 months of age were studied. Levels of lipid peroxidation (LPO), glutathione (GSH), GSH disulfide (GSSG), and GSH peroxidase and GSH reductase (GRd) activities were measured. In addition, the effect of chronic treatment with the antioxidant melatonin from 1 to 10 months of age was evaluated. Cardiac and diaphragmatic mitochondria show an age-dependent increase in LPO levels and a reduction in GSH:GSSG ratios. Chronic treatment with melatonin counteracted the age-dependent LPO increase and GSH:GSSG ratio reduction in these mitochondria. Melatonin also increased GRd activity, an effect that may account for the maintenance of the mitochondrial GSH pool. Total mitochondrial content of GSH increased after melatonin treatment. In general, the effects of age and melatonin treatment were similar in senescence-resistant mice (SAMR1) and SAMP8 cardiac and diaphragmatic mitochondria, suggesting that these mice strains display similar mitochondrial oxidative damage at the age of 10 months. The results also support the efficacy of long-term melatonin treatment in preventing the age-dependent mitochondrial oxidative stress.
对5月龄或10月龄雄性SAMP8(衰老)和SAMR1(抗性)小鼠的心脏和膈肌线粒体进行了研究。测量了脂质过氧化(LPO)、谷胱甘肽(GSH)、谷胱甘肽二硫化物(GSSG)水平以及谷胱甘肽过氧化物酶和谷胱甘肽还原酶(GRd)活性。此外,评估了从1月龄到10月龄用抗氧化剂褪黑素进行慢性治疗的效果。心脏和膈肌线粒体显示LPO水平随年龄增长而增加,GSH:GSSG比值降低。用褪黑素进行慢性治疗可抵消这些线粒体中随年龄增长的LPO增加和GSH:GSSG比值降低。褪黑素还增加了GRd活性,这一作用可能解释了线粒体GSH池的维持。褪黑素治疗后,线粒体GSH的总含量增加。总体而言,在抗衰老小鼠(SAMR1)以及SAMP8小鼠的心脏和膈肌线粒体中,年龄和褪黑素治疗的效果相似,这表明在10月龄时,这些小鼠品系表现出相似的线粒体氧化损伤。研究结果还支持长期褪黑素治疗在预防随年龄增长的线粒体氧化应激方面的有效性。