Changes in Concentration of Essential Metals in Kidneys and Urine as Indices of Gentamicin Nephrotoxicity in Female Wistar Rats

Abstract

Wistar rats were treated with gentamicin in single (80 mg/kg) or repeated doses (7 x 40 mg/kg) subcutaneously. Total protein as well as excretion of essential metals (Cu, Zn) with the urine were determined 24 hr after 1, 3 and 7 dosages as well as 3 and 7 days after the termination of administration. At the same time kidneys were examined histopathologically by light microscopy. Simultaneously, Cu, Zn and metallothionein levels in kidneys and liver were determined. Rats receiving gentamicin demonstrated progressive renal proximal tubular necrosis at the end of 7 days administration. At the same time elevated copper and zinc levels were observed in urine. These essential metals seem to be an indicator of gentamicin nephrotoxicity.

Essential Elements as Early Indicators of Hexavalent Chromium Nephrotoxicity

“…However, it should also be noted that numerous metals, such as nickel, tin, lead, and cobalt, do not induce metallothionein but still cause renal damage accompanied by increased copper and zinc excretion in the urine (Chmielnicka et al, , 1982Chmielnicka, 1991;Rassenberg and Kappas, 1989). It was also noted that the levels of metallothionein in gentamicin-exposed rats were not changed, but elevated copper and zinc levels in urine that were parallel to histopatologic changes in kidneys were observed (Chmielnicka et al, 1992). In the case of exposure to chromium, no changes of metallothionein in kidney and liver of rats were observed compared to control animals (Fig.…”

Increased urinary zinc excretion in cancer patients is linked to immune activation and renal tubular cell dysfunction

“…Both an increase in primary urine zinc concentration resulting from skeletal muscle catabolism with subsequent release of zinc bound to low molecular weight ligands (Fell et al 1973) and renal tubular cell dysfunction (Boosalis et al 1991, Yuzbasiyan-Gurkan et al 1989 have been invoked to explain this phenomenon. Hyperzincuria was observed in experi-mental renal tubular cell necrosis (Chmielnicka et al 1992) and could be produced by injection of killed bacteria in experimental animals (Klaiman et al 1981, Kirby et al 1982.…”

“…Recently, however, increased urine zinc was shown to be associated with renal tubular cell dysfunction (YuzbasiyanGurkan et al 1989, Boosalis et al 1991. Elevated urine zinc excretion was also shown to accompany experimental renal tubular cell necrosis (Chmielnicka et al 1992). Urinary zinc excretion in cancer patients was demonstrated to correlate with urine concentrations of neopterin, an index of systemic immune activation .…”