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.

Maternal L‐carnitine supplementation ameliorates renal underdevelopment and epigenetic changes in male mice offspring due to maternal smoking

“…Our results may suggest that LC‐mediated reduction of FGF2 at weaning may potentially prevent fibrogenesis in the long term. Indeed, in our previous study, the renal expression of the inflammatory marker MCP‐1 in adulthood was significantly reduced in SE offspring if the mothers had LC supplementation during gestation and lactation compared to those from the SE mothers without intervention . The long‐term anti‐inflammatory effect of maternal LC supplementation in the kidneys of the adult offspring is consistent with a previous study …”

“…In rodents, LC supplementation has been shown to improve atherosclerosis and chronic renal failure induced by partial nephrectomy . In addition, LC has been shown to be essential in fetal development and intrauterine maturation of the brain and lung; we have recently demonstrated that maternal LC supplementation during gestation and lactation reversed small body weight and kidney weight at birth, as well as normalising renal oxidative stress and renal dysfunction due to maternal SE in the male offspring . However, the effect of LC on epigenetic signatures and renal developmental markers is not known.…”

“…Prenatal smoke exposure (SE) has been associated with reduced kidney volume in the offspring . Using an animal model of maternal smoking, we have previously demonstrated that maternal smoking induces renal underdevelopment and oxidative stress in the offspring from birth and this was associated with renal dysfunction at adulthood …”

Protective Effects of Hydrogen Sulfide Against Cigarette Smoke Exposure-Induced Placental Oxidative Damage by Alleviating Redox Imbalance via Nrf2 Pathway in Rats

“…Together, these SOD enzymes scavenge superoxide anion into molecular oxygen and hydrogen peroxide, then CAT and GPx reduce hydrogen peroxide, thus preventing production of highly toxic hydroxyl radical [64]. Growing evidence indicates that cigarette smoking or CSE significantly decrease the activities of anti-oxidative enzymes both in vitro and in vivo researches [65,66]. In the present study, our results displayed a significant reduction in activities of SOD1, SOD2, CAT and total GPx in CSE rat placentas, however, the decreased activities of the anti-oxidative enzymes were improved with NaHS application.…”

Metabolomic similarities between bronchoalveolar lavage fluid and plasma in humans and mice

“…However, L-carnitine has been shown to improve symptoms in children with moderate persistent asthma when administered orally 43 . Dietary supplementation of L-carnitine has also been shown to reverse renal oxidative stress and mitochondrial dysfunction in female BALB/c mice who were exposed to cigarette smoke 44 . In a recent study, L-carnitine decreased with emphysema progression in mice, and L-carnitine supplementation improved lung function and reduced apoptosis 13 .…”