Abnormal auditory brainstem responses for mice treated with mercurial compounds: involvement of excessive nitric oxide

In this paper, we attempted to construct an animal (mouse) model for monito ring the oto-neurotoxicity of mercuric sulfide, comparing its toxicity with the well-known (organic) mercury compound methyl-mercury. Mice were treate d with either mercuric sulfide (HgS, 0.1 and 1.0 g/kg per day) or methyl-me rcury (MeHg, 0.2, 2.0 and 10 mg/kg per day) by gastric gavage for 7 consecu tive days. Analysis of auditory brainstem response (ABR) indicated that sig nificant elevation of the physiological hearing threshold as well as signif icant prolongation of interwave latency I-V was observed for MeHg - (2.0 an d 0.2 mg/kg per day) or HgS - (1.0 g/kg per day, but not 0.1 g/kg per day) treated mice. Further, both MeHg- and HgS-treated animals demonstrated a si gnificant prolongation of interwave latency I-V that increased with an incr easing mean blood-Hg level. The oto-neurotoxicity of MeHg (2.0 mg/kg per da y) persisted to at least 11 weeks subsequent to the cessation of its admini stration. The toxic effect of HgS, however, disappeared completely 5 weeks subsequent to the cessation of its administration. These results suggest a correlation between the Hg-elicited hearing dysfunction and the availabilit y of mercury in brain tissue. Both inhibition of Na+/K+-ATPase activity and overproduction of nitric oxide in the brainstem are consistent with an ana lysis of the physiological hearing threshold and latencies of ABR waveform at all time points throughout the experimental process. Thus, it is propose d that high-dose HgS or MeHg intoxication is associated with a decrease in functional Na+/K+-ATPase activity in the brainstem of affected animals, thi s presumably arising via excessive nitric oxide production, and suggesting that brainstem damage may play a role in mercury-induced hearing loss. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.