Nguyen Long T, Stangenberg Stefanie, Chen Hui, Al-Odat Ibrahim, Chan Yik L, Gosnell Martin E, Anwer Ayad G, Goldys Ewa M, Pollock Carol A, Saad Sonia
School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology Sydney, Sydney, New South Wales, Australia;
Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia; and.
Am J Physiol Renal Physiol. 2015 Apr 1;308(7):F689-96. doi: 10.1152/ajprenal.00417.2014. Epub 2015 Jan 21.
Maternal smoking is associated with metabolic disorders, renal underdevelopment, and a predisposition to chronic kidney disease in offspring, yet the underlying mechanisms are unclear. By exposing female Balb/c mice to cigarette smoke for 6 wk premating and during gestation and lactation, we showed that maternal smoke exposure induced glucose intolerance, renal underdevelopment, inflammation, and albuminuria in male offspring. This was associated with increased renal oxidative stress and mitochondrial dysfunction at birth and in adulthood. Importantly, we demonstrated that dietary supplementation of l-carnitine, an amino acid shown to increase antioxidant defenses and mitochondrial function in numerous diseases, in smoke-exposed mothers during pregnancy and lactation significantly reversed the detrimental maternal impacts on kidney pathology in these male offspring. It increased SOD2 and glutathione peroxidase 1, reduced ROS accumulation, and normalized levels of mitochondrial preprotein translocases of the outer membrane, and oxidative phosphorylation complexes I-V in the kidneys of mouse progeny after intrauterine cigarette smoke exposure. These findings support the hypothesis that oxidative stress and mitochondrial dysfunction are closely linked to the adverse effects of maternal smoking on male offspring renal pathology. The results of our study suggest that l-carnitine administration in cigarette smoke-exposed mothers mitigates these deleterious renal consequences.
母亲吸烟与后代的代谢紊乱、肾脏发育不全以及患慢性肾病的倾向有关，但其潜在机制尚不清楚。通过在交配前6周以及妊娠和哺乳期将雌性Balb/c小鼠暴露于香烟烟雾中，我们发现母体烟雾暴露会导致雄性后代出现葡萄糖不耐受、肾脏发育不全、炎症和蛋白尿。这与出生时和成年后的肾脏氧化应激增加以及线粒体功能障碍有关。重要的是，我们证明，在孕期和哺乳期给暴露于烟雾中的母亲补充左旋肉碱（一种在许多疾病中显示可增强抗氧化防御和线粒体功能的氨基酸），可显著逆转母体对这些雄性后代肾脏病理的有害影响。它增加了超氧化物歧化酶2和谷胱甘肽过氧化物酶1，减少了活性氧的积累，并使子宫内暴露于香烟烟雾的小鼠后代肾脏中的线粒体外膜前体蛋白转位酶以及氧化磷酸化复合体I-V的水平恢复正常。这些发现支持了氧化应激和线粒体功能障碍与母体吸烟对雄性后代肾脏病理的不利影响密切相关的假设。我们的研究结果表明，给暴露于香烟烟雾的母亲服用左旋肉碱可减轻这些有害的肾脏后果。
