Alterations of Oxidative Stress Biomarkers Due to In Utero and Neonatal Exposures of Airborne Manganese

Abstract

Neonatal rats were exposed to airborne manganese sulfate (MnSO4) (0, 0.05, 0.5, or 1.0 mg Mn/m3) during gestation (d 0-19) and postnatal days (PNDs) 1-18. On PND 19, rats were killed, and we assessed biochemical end points indicative of oxidative stress in five brain regions: cerebellum, hippocampus, hypothalamus, olfactory bulb, and striatum. Glutamine synthetase (GS) and tyrosine hydroxylase (TH) protein levels, metallothionein (MT), TH and GS mRNA levels, and reduced and oxidized glutathione (GSH and GSSG, respectively) levels were determined for all five regions. Mn exposure (all three doses) significantly (p = 0.0021) decreased GS protein levels in the cerebellum, and GS mRNA levels were significantly (p = 0.0008) decreased in the striatum. Both the median and high dose of Mn significantly (p = 0.0114) decreased MT mRNA in the striatum. Mn exposure had no effect on TH protein levels, but it significantly lowered TH mRNA levels in the olfactory bulb (p = 0.0402) and in the striatum (p = 0.0493). Mn exposure significantly lowered GSH levels at the median dose in the olfactory bulb (p = 0.0032) and at the median and high dose in the striatum (p = 0.0346). Significantly elevated (p = 0.0247) GSSG, which can be indicative of oxidative stress, was observed in the cerebellum of pups exposed to the high dose of Mn. These data reveal that alterations of oxidative stress biomarkers resulting from in utero and neonatal exposures of airborne Mn exist. Coupled with our previous study in which similarly exposed rats were allowed to recover from Mn exposure for 3 wk, it appears that many of these changes are reversible. It is important to note that the doses of Mn utilized represent levels that are a hundred- to a thousand-fold higher than the inhalation reference concentration set by the United States Environmental Protection Agency.