Neurotoxicological effects of low-dose methylmercury and mercuric chloride in developing offspring mice.

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, 0.02mg/kg/day) and mercury chloride (HgCl(2)) (H, 0.5mg/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-HgCl(2) (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 HgCl(2)-HgCl(2) (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 (NO(x)) 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/NO(x) plays a crucial role in the underlying mechanism for mercurial compound-induced toxic effects in offspring.

• Authors: Chun-Fa Huang, Shing-Hwa Liu, Chuan-Jen Hsu, Shoei-Yn Lin-Shiau
• Journal: Toxicology letters (Toxicol Lett) Vol. 201 Issue 3 Pg. 196-204 (Mar 25 2011) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 21195143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011. Published by Elsevier Ireland Ltd.

Chemical References

• Methylmercury Compounds
• Nitric Oxide
• Mercuric Chloride
• Sodium-Potassium-Exchanging ATPase
• Mercury

Topics

• Animals
• Auditory Threshold (drug effects)
• Body Weight (drug effects)
• Brain (metabolism)
• Evoked Potentials, Auditory, Brain Stem (drug effects)
• Female
• Fetus (drug effects)
• Lipid Peroxidation (drug effects)
• Male
• Mercuric Chloride (toxicity)
• Mercury (metabolism)
• Mercury Poisoning, Nervous System (pathology)
• Methylmercury Compounds (toxicity)
• Mice
• Mice, Inbred ICR
• Motor Activity (drug effects)
• Nitric Oxide (metabolism)
• Oxidative Stress (drug effects)
• Postural Balance (drug effects)
• Pregnancy
• Prenatal Exposure Delayed Effects
• Sodium-Potassium-Exchanging ATPase (metabolism)