Neurotoxicological effects of low-dose methylmercury and mercuric chloride in developing offspring mice |
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Authors: | Huang Chun-Fa Liu Shing-Hwa Hsu Chuan-Jen Lin-Shiau Shoei-Yn |
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Affiliation: | a School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan b Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan c Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan d Department of Otolaryngology, College of Medicine, National Taiwan University, Taipei, Taiwan |
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Abstract: | Mercury is a well-known toxic metal and potently induces severe neurotoxicological effects, especially in infants and children. The purpose of this study was to explore the underlying mechanisms of neurotoxic effects of mercurial compounds on the different stages of developing mice. Low-doses (the probability of human exposure in mercury-contaminated areas) of methylmercury (MeHg) (M, 0.02 mg/kg/day) and mercury chloride (HgCl2) (H, 0.5 mg/kg/day) were administered to mice of the following groups: (1) treatment with distilled water for 7 consecutive weeks after weaning (control-vehicle (CV)); exposure to mercurial compounds at different stages; (2) for 7 consecutive weeks after weaning (control-MeHg (CM) and control-HgCl2 (CH)); (3) only during perinatal and weaning stages (MeHg-vehicle (MV) and HgCl-vehicle (HV)); and (4) in all experimental stages (MeHg-MeHg (MM) and HgCl2-HgCl2 (HH)). Results revealed the neurobehavioral defects (increased locomotor activities, motor equilibrium impairment, and auditory dysfunction) that correlated with increasing Hg accumulation in CM and CH groups. However, it revealed a decrease and an increase in locomotor activities in MV and HV groups, respectively; these became more severe in MM and HH groups than in MV and HV groups. Motor equilibrium performance in MV and HV groups remained normal, while that in MM and HH groups was decreased. The most severe auditory defects (altered auditory brainstem response, ABR test) found in MM and HH groups than those in the respective CM and CH, MV and HV, including absolute wave III delays and interwave I-III latencies, which suggested that the irreversible auditory dysfunction caused by mercurial compounds. Furthermore, the alteration of lipid peroxidation (LPO), Na+/K+-ATPase activities, and nitric oxide (NOx) in the brain tissues contributed to the observed neurobehavioral dysfunction and hearing impairment. These findings provide evidence that fetuses were much more susceptible to the effects of mercurial compounds with regard to inducing severely neurotoxicological injuries as that found in human beings. The signaling of ROS/Na+-K+-ATPase/NOx plays a crucial role in the underlying mechanism for mercurial compound-induced toxic effects in offspring. |
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Keywords: | MeHg, methylmercury HgCl2, mercury chloride CV, control-vehicle CM, control-MeHg CH, control-HgCl2 MV, MeHg-vehicle HV, HgCl2-vehicle MM, MeHg-MeHg HH, HgCl2-HgCl2 ABR, auditory brainstem response LPO, lipid peroxidation NOx, nitric oxide BBB, blood-brain barrier ROS, reactive oxygen species MDA, malondialdehyde ICP-MS, inductively coupled plasma mass spectrometry |
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