L-Carnitine mitigates impact of maternal smoking on lung health in mice offspring

Abstract

Cigarette smoke exposure (SE) during pregnancy is the largest modifiable risk factor for the development of asthma. We have previously shown that maternal L-Carnitine treatment reduces renal and brain adverse impacts in SE offspring, but its effect on the lung is unknown. Here, in order to investigate the effect of maternal L-Carnitine supplementation on lungproinflammatory signalling pathwayswe measured inflammasome NLRP3 activation, signalling pathway activation (ERK1,2, JNK1,2, MAPK, and NF-KB), and markers of autophagy (LC3A/B-I, II) and mitophagy (Drp-1 and Opa-1). Female Balb/c mice (8 weeks) were exposed to cigarette smoke before mating for 6 weeks, during gestation and lactation. Half SE mothers were given L-Carnitine supplementation through drinking water during gestation and lactation. Lung samples were collected at postnatal day 1 and 13 weeks from both male and female offspring. At P1, there was an increase in phospho-ERK1,2, total ERK1,2, total JNK1,2, phospho-P38 MAPK and P38 MAPK, phospho-NFKB, NFKB and NLPR3 protein levels in male offspring. The mitochondrial fission marker Drp-1 and autophagosome markers (LCA3A/B-I,II) were increased in SE offspring, L-Carnitine significantly reduced protein levels of phospho-ERK1 and Drp-1. At 13 weeks, there was an increase in autophagosome markers (LCA3A/B-I,II) and MAPK signaling pathway markers (phospho-ERK2, total ERK2, total P38 MAPK and phospho-NFKB), which were partially normalized by L-Carnitine treatment. Maternal SE did not affect the female offspring with no changes found after L-Carnitine treatment. L-Carnitine supplementation during pregnancy may alleviate the adverse impact of maternal smoking in the male offspring’s lung.