[HgCl2-induced acute renal failure and its pathophysiology].
Mercury chloride (HgCl2) has a potent nephrotoxic effect. Most of Hg2+ existing in plasma following HgCl2 exposure forms a complex with sulfhydryl-containing ligands such as albumin and glutathione (GSH). The Hg(2+)-GSH complex is filtered in the glomeruli of the kidney and degraded into Hg(2+)-cysteine in the proximal tubules by the combined action of gamma-glutamyl transpeptidase and dipeptidase present in the epithelial cells. The degradation product is then incorporated and accumulated into the proximal tubule epithelial cells. The accumulated Hg2+ in the epithelial cells finally causes acute tubular necrosis (ATN) by its cytotoxic effect. At present, it is believed that tubular obstruction resulting from ATN triggers the onset of HgCl2-induced acute renal failure (ARF). A progressive fall in glomerular filtration rate (GFR) contributes to the progression of HgCl2-induced ARF. The fall in GFR may be caused by an increment in afferent arteriole resistance (RA) and a decrement in the ultrafiltration coefficient (Kf) due to mesangial cell contraction. These changes in RA and Kf may be attributed to the increased action of the vasoconstrictors, angiotensin II and endothelin-1 and to the decreased action of the vasodilator, nitric oxide observed at the glomerulus level of HgCl2-induced ARF. Accordingly, the imbalance between these vasoactive substances appears to play an important role in the progression of HgCl2-induced ARF due to reducing GFR. Further studies, however, remain to elucidate the mechanisms involved.
Yanagisawa
H
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Department of Hygiene & Preventive Medicine, Saitama Medical School, Japan.
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000503:physiopathology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D018450:Disease Progression; D019332:Endothelin-1 / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006801:Humans; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced; D008627:Mercuric Chloride / Q000633:toxicity*; D014655:Vascular Resistance
D019332:Endothelin-1; D000804:Angiotensin II; D008627:Mercuric Chloride