title: In utero and lactational β-carotene supplementation attenuates D-galactose-induced hearing loss in newborn rats.
abstract: D-Galactose could give rise to free radical damage by disturbing the some maternal antioxidants. The oxidative stress induced by D-galactose is a potent inducer of apoptosis, which is accompanied by the activation of protein-splitting enzymes called caspases. Apoptosis is a crucial physiological determinant of embryonic and neonatal development, and play an essential role in the development of the inner ear structures. Recently the increasing of D-galactose exposure is due to high consumption of dairy foods or reduced galactose metabolism. An overwhelming presence of D-galactose is known to become highly ototoxicity to humans. The purpose of this study was to investigate whether supplementation of pregnant and lactational mothers with β-carotene could attenuate cochlear function damage and hair cells apoptosis induced by d-galactose in newborn rats. Pregnant rats were supplemented with D-galactose, or D-galactose and β-carotene from gestational day (GD) 7 until postnatal day (PND) 21. On PND 22, offspring were examined in the distortion product otoacoustic emission (DPOAE) task, cochleae were then harvested for assessment of apoptosis by immunohistochemical stain for cysteine-aspartic acid proteases 3 (caspase-3) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Maternal and offspring blood samples were then collected by direct cardiac puncture in heparin tubes, blood levels of D-galactose and β-carotene were measured, plasma was separated for malondialdehyde (MDA) analysis, erythrocytes were left for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH). D-Galactose could significantly disturb the balance between maternal antioxidants and free radicals, and induce hearing loss in the offspring and cochlear hair cell apoptosis. In contrast, β-carotene supplementation, coincidentally with D-galactose exposure, ameliorated these changes. Our data offer a conceptual framework for designing clinical trials using a safe micronutrient, β-carotene, as a simple preventive strategy for D-galactose-induced ototoxicity.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Heping District, Shenyang, Liaoning 110001, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Shuai
authors.initials: S
authors.lastname: Hao
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Fan
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D019587:Dietary Supplements; D005260:Female; D005690:Galactose / Q000633:toxicity*; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D034381:Hearing Loss / Q000139:chemically induced* / Q000188:drug therapy*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007774:Lactation; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018811:Maternal Exposure; D018384:Oxidative Stress; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D061945:Caspase Inhibitors; D019207:beta Carotene; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione; D005690:Galactose