title: L-Carnitine reverses maternal cigarette smoke exposure-induced renal oxidative stress and mitochondrial dysfunction in mouse offspring.
abstract: 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.
authors.affiliation: School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology Sydney, Sydney, New South Wales, Australia;
authors.forename: Long T
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia; and.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Stangenberg
authors.affiliation: School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology Sydney, Sydney, New South Wales, Australia;
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology Sydney, Sydney, New South Wales, Australia;
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Al-Odat
authors.affiliation: School of Medical and Molecular Biosciences, Faculty of Science, Centre for Health Technology, University of Technology Sydney, Sydney, New South Wales, Australia;
authors.forename: Yik L
authors.initials: YL
authors.lastname: Chan
authors.affiliation: MQ BioFocus Research Centre, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gosnell
authors.affiliation: MQ BioFocus Research Centre, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Ayad G
authors.initials: AG
authors.lastname: Anwer
authors.affiliation: MQ BioFocus Research Centre, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Goldys
authors.affiliation: Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia; and.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Pollock
authors.affiliation: Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia; and sonia.saad@sydney.edu.au.
authors.forename: Sonia
authors.initials: S
authors.lastname: Saad
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002331:Carnitine / Q000494:pharmacology*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012907:Smoking; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D014803:Vitamin B Complex; D002331:Carnitine
keywords: chronic kidney disease; mitochondria; reactive oxidative species