Toxic nephropathy: environmental chemicals
Section snippets
Mercury
Mercury, like cadmium, gold, lead, nickel, chromium, and uranium, is a nephrotoxic metal.1 Mercury can exist in 3 oxidation states: elemental mercury (Hg0), mercurous mercury (Hg1+), and mercuric mercury (Hg2+). Hg0 is a ubiquitous environmental pollutant introduced primarily by degassing of the earth’s crust and is oxidized to Hg2+ in mammalian cells.2 Organomercurials, such as methyl mercury, are produced by microbial metabolism of both Hg0 and Hg2+.3 Organomercurials are hydrophobic and
Trichloroethylene
Trichloroethylene (TCE) is a widely used industrial solvent and a common environmental contaminant. Although TCE exposures may come from contaminated drinking water, higher-level exposures are more likely to originate from occupational exposures. Although the kidney is not a selective target of TCE directly, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), a biotransformation product of TCE, is a nephrotoxicant in several mammalian species. DCVC offers an additional example of how GSH and cysteine
Paraquat/diquat
Paraquat and diquat are structurally similar nonselective herbicides. When used properly these compounds offer no significant risk to humans, partly because the intact skin provides a significant barrier against penetration. However, most poisonings occur from accidental ingestion or in cases of attempted suicide. Interestingly, diquat solutions as low as 1% have resulted in human toxicity.27 When ingested, these compounds cause multisystem toxicity to the lung, kidney, heart, and central
Ethylene glycol
Ethylene glycol (EG) is an antifreeze in cooling systems, a component of hydraulic brake fluid, an ingredient in chemical synthesis, and a solvent. Further, EG also has been used to de-ice airplanes and runways. Life-threatening human exposures to EG generally occur from ingestion of large quantities in attempted suicides. Dogs and cats, 2 species prone to accidental EG poisonings,31 have shown signs of nephrotoxicity after ingestion of mishandled EG sources.
EG-mediated renal toxicity requires
Herbal remedies
Aristolochic acids, plant alkaloid products of the Chinese herb Aristolochia fangchi, are nephrotoxic. Between 1990 and 1992, renal failure developed in young Belgian woman who were on a slimming regimen containing Chinese herbs. The rapidly fibrosing nephropathy is now described as Chinese herbs nephropathy (CHN). About 100 cases of CHN have been identified in Belgium, with approximately half of them requiring renal transplantation.34 In 1994, the presence of aristolochic acids in diet pills,
Summary
Because of the unique anatomy, biochemistry, and physiology of the kidney, it is the target of numerous environmental chemicals. The toxicants discussed in this article show several mechanisms by which the kidney is targeted by xenobiotics. The ability of the kidneys to selectively accumulate GSH-conjugate species of chemicals such as TCE, bromobenzene, and mercury make it the target of these toxicants and various drugs. What remains to be accomplished and by far the most difficult process is
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2019, Pharmacological ReportsCitation Excerpt :The sensitivity of the kidney to various environmental substances may be due to it's anatomical, biochemical or physiological features. Factors that lead to the sensitivity of the kidney include increased blood flow, the presence of different types of xenobiotic carriers and metabolizing enzymes in the kidney [19]. For this reason, there is a critical need for the usage of natural products for the treatment of numerous diseases since they are highly available and show fewer side effects.
Mercury-induced inflammation and autoimmunity
2019, Biochimica et Biophysica Acta - General SubjectsCitation Excerpt :This contrasts to T-dependent humoral immune responses which are not dependent on nucleic acid TLR signaling [154,155]. Tissue pathology following mercury exposure involves both toxic [156] and immunological facets [101]. Continued exposure can be fatal, however this appears to be a toxic rather than immune mediated outcome as lethal proteinuria is rare in the absence of idiopathic autoimmunity [131].