PROTECTIVE EFFECT OF L-CARNITINE IN MATERNAL SMOKING INDUCED RENAL MITOCHONDRIAL DYSFUNCTION  — The Association Specialists
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  3. PROTECTIVE EFFECT OF L-CARNITINE IN MATERNAL SMOKING INDUCED RENAL MITOCHONDRIAL DYSFUNCTION 

PROTECTIVE EFFECT OF L-CARNITINE IN MATERNAL SMOKING INDUCED RENAL MITOCHONDRIAL DYSFUNCTION  (335)

Long T Nguyen 1 , Stefanie Stangenberg 2 , Ibrahim Al Odat 1 , Carol Pollock 2 , Hui Chen 1 , Sonia Saad 2
  1. School of Medical and Molecular Sciences, Faculty of Science, University of Technology, Sydney, NSW, Australia
  2. Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia

Background: Our recent work in mice has indicated that intrauterine cigarette smoke exposure (SE) can increase renal oxidative stress and mitochondrial dysfunction in offspring’s kidney. This was closely linked to renal under-development and renal functional disorders in adulthood. L-carnitine, synthesized in the liver and kidney, is involved in mitochondrial fatty acid metabolism and ATP synthesis. It can act as an antioxidant and has been shown to attenuate oxidative injury in renal proximal tubule cells.

Aims: To determine whether L-carnitine supplementation during gestation and lactation can attenuate renal oxidative stress and mitochondrial dysfunction by maternal cigarette smoke exposure (SE) in the offspring.

Methods: Female Balb/c mice were exposed to cigarette smoke for 6 weeks preconception, and during conception and lactation periods. L-carnitine was provided in drinking water to the SE mothers during conception and lactation periods only. Offspring were sacrificed at postnatal day (P) 1, P20 and week 13; kidneys were then examined for kidney development by histology, oxidative stress by reactive oxygen species (ROS) assay, as well as antioxidative markers (MnSOD, GPx-1) and mitochondrial function (TOM20 and Oxidative phosphorylation (OXPHOS) complexes I – V) by Western blotting and immunohistochemistry.

Results: Offspring from the SE mothers had delayed renal development at P1 and P20. Their kidneys showed significant reductions of MnSOD, TOM20 and OXPHOS at P1, which were improved at P20 and mostly recovered by week 13. SE offspring treated with L-carnitine showed normal renal levels of all examined markers at P1, and antioxidative markers at P20. 

Conclusions: Maternal SE leads to increased oxidative stress, decreased antioxidative markers and mitochondrial dysfunction. Supplementation of L-carnitine during pregnancy and lactation benefits renal antioxidative capacity and mitochondrial function in the SE offspring, holding a great potential for preventative and therapeutic applications to renal disorders in the offspring due to maternal SE.