The interaction of mercurials with myelin: comparison of in vitro and in vivo effects.
Our previous study on the in vitro interactions of mercurials with peripheral nerve had shown that HgCl2 labels phosphatidylethanolamine plasmalogen in the myelin membrane, and that both HgCl2 and CH3HgCl alter the packing of the membrane array (Kirschner and Ganser, 1982). Thin-layer chromatography shows that in vitro treatment of sciatic and optic nerve with HgCl2 causes the hydrolysis of phosphatidylethanolamine plasmalogen while treatment with CH3HgCl does not. The present study addresses the possibility that the interaction of mercurials with myelin phosphatidylethanolamine plasmalogen may underlie their neurotoxicity. HgCl2 was administered to different groups of mice by intravenous, intraperitoneal and subcutaneous injections, and perorally through their drinking water. CH3HgCl was given perorally. Elemental mercury (Hg degree) vapor was administered by inhalation. The mice were monitored for signs of neurotoxicity. Myelin labeling and structure in sciatic and optic nerves was examined using X-ray diffraction and histochemical electron microscopy. The levels of mercury in tissues were measured using atomic absorption spectrophotometry. Mice exposed to CH3HgCl or to Hg degree vapor developed neurological symptoms, while mice exposed to HgCl2 did not show dysfunction even after doses as high as 10-20 mg/kg/day for 14 months. Neither labeling of the myelin membrane nor changes in membrane packing were detected in nerves from mice treated with either mercurial or with Hg degree. These nerves did not show any histochemical evidence for mercury deposition in the myelin, whereas in vitro treated nerves did. The level of mercury in sciatic and optic nerves from mice intoxicated with CH3HgCl was measurable, but at least 30-40 times less than that after in vitro treatment. With HgCl2 intoxication, no measurable amount of mercury was detected in these nerves. Exposure to Hg degree vapor resulted in low but detectable levels of mercury in the nerves. We conclude from these results that the neurotoxicity of mercurials does not involve their interaction with lamellar myelin.
D000818:Animals; D002855:Chromatography, Thin Layer; D066298:In Vitro Techniques; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008627:Mercuric Chloride / Q000633:toxicity; D008628:Mercury / Q000378:metabolism / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D014018:Tissue Distribution; D014961:X-Ray Diffraction
D008563:Membrane Lipids; D008767:Methylmercury Compounds; D010743:Phospholipids; D008627:Mercuric Chloride; D008628:Mercury; C004925:methylmercuric chloride