Lipid peroxidation, mercuric mercur

Huang YL, Cheng SL, Lin TH (1996) Lipid peroxidation in rats administrated with mercuric chloride. Biol Trace Elem Res 52(2) 193-206... 

Oral or parenteral administration of mercuric chloride promotes lipid peroxidation [127-129], possibly via a reduction of glutathione peroxidase activity. However, several studies argue against lipid peroxidation being responsible, at least for the early hours of cell toxicity of mercury [130-133]. 

Organic mercurials are capable of inducing nephrotoxicity in S2 and S3 segments of the proximal tubule. Part of the S3 damage results from the biotransformation of the organic mercurial to release mercuric ions. Methylmercury (CH3Hg + ) readily concentrates in renal proximal tubular cells and alters mitochondrial function and lysosomes. At least part of methylmercury-induced nephrotoxicity may be due to homolytic scission of methylmercury to release methyl radicals and to lipid peroxidative toxicity. 

The data indicate that zinc-induced metallothionein binds mercury in the renal cortex and shifts the distribution of mercury from its site of toxicity at the epithelial cells of the proximal tubules. Thus, the renal content of mercury is increased, yet less is available to cause toxicity. In contrast, the renal toxicity of mercuric chloride is exacerbated in zinc-deficient animals (Fukino et al. 1992). In the zinc-deficient state, less mercury accumulates in the kidneys, but the toxicity is greater. The mechanism of the protection appears to involve more than simply a redistribution of renal mercury, because in the absence of mercury exposure, zinc deficiency increases renal oxidative stress (increased lipid peroxidation, decreased reduced ascorbate). When mercury exposure occurs, the oxidative stress is compounded (increased lipid peroxidation and decreased glutathione and glutathione peroxidase). Thus, zinc appears to affect the biochemical protective mechanisms in the kidneys as well. 

Andersen, H R., and O. Andersen. 1993. Effects of dietary alpha-tocopherol and beta- carotene on lipid peroxidation induced by methyl mercuric chloride in mice. Pharmacol. Toxicol. 73 (4) 192-201. 

Both the plasma membrane and internal membranes associated with organelles may be damaged by toxic compounds. As already discussed, this may be due to lipid peroxidation which alters and destroys membrane lipids. As many enzymes and transport processes are membrane bound this will affect the function of the organelle as well as the structure. Sulphydryl groups in membranes may be targets for mercuric ions in kidney tubular cells and for methyl mercury in the CNS for example. The result is changes in membrane permeability and transport and subsequent cell death. Structural damage can be... 

Fukino, H., Hirai, M., Hsueh, Y.M., Yamane, Y., 1984. Effect of zinc pretreatment on mercuric chloride-induced lipid peroxidation in the rat kidney. Toxicol. Appl. Pharmacol. 3, 395 01. 

---