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Titolo:
Metallothionein protects against the nephrotoxicity produced by chronic CdMT exposure
Autore:
Liu, YP; Liu, J; Habeebu, SM; Klaassen, CD;
Indirizzi:
Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Ctr Environm Hlth & Occupat Med, Kansas City, KS 66160 USA Univ Kansas Kansas City KS USA 66160 cupat Med, Kansas City, KS 66160 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 2, volume: 50, anno: 1999,
pagine: 221 - 227
SICI:
1096-6080(199908)50:2<221:MPATNP>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROXIMAL CONVOLUTED TUBULES; CADMIUM-METALLOTHIONEIN; II GENES; CHLORIDE; CELLS; HEPATOTOXICITY; ACCUMULATION; NEPHROPATHY; LETHALITY; TOXICITY;
Keywords:
cadmium; CdMT; MT-null mice; renal Cd concentration; nephrotoxicity; urinary protein and NAG; blood urea nitrogen;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Klaassen, CD Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, CtrEnvironm Hlth & Occupat Med, 3901 Rainbow Blvd, Kansas City, KS 66160 USA Univ Kansas 3901 Rainbow Blvd Kansas City KS USA 66160 60 USA
Citazione:
Y.P. Liu et al., "Metallothionein protects against the nephrotoxicity produced by chronic CdMT exposure", TOXICOL SCI, 50(2), 1999, pp. 221-227

Abstract

Metallothionein (MT) is a low-molecular-weight, cysteine-rich, metal-binding protein. Induction of MT has been proposed to be an important adaptive mechanism in decreasing Cd toxicity. MT has been shown to protect against CdCl2-induced lethality and hepatotoxicity; however, MT does not protect against acute CdMT-induced nephrotoxicity. This study was aimed at clarifying the role of metallothionein in chronic CdMT-induced renal injury. Wild type and MT-I/II knockout (MT-null) mice were therefore given sc injections of CdMT (25 and 100 mu g Cd/kg) or saline daily, 6 times/week for 6 weeks, and renal injury was evaluated. Multiple injections of CdMT to wild-type mice resulted in renal Cd concentrations up to 120 mu g/g kidney, along with a 100-fold increase in renal MT (450 mu g/g kidney). In contrast, renal Cd concentration in MT-null mice administered multiple injections of CdMT reached a much lower level than in wild-type mice (<10 mu g/g kidney). Although less Cd accumulated in their kidneys, MT-null mice were more susceptible than wild-type mice to CdMT induced nephrotoxicity, as indicated by increased urinary excretion of protein and N-acetyl-beta-D-glucosaminidase, as well as by elevated blood urea nitrogen levels. At the higher daily dose of CdMT (100 mu g Cd/kg), kidneys of MT-null mice were enlarged. Chronic CdMT administration eventually damaged the entire kidney, which included glomerular swelling, interstitial inflammation, edema, tubular cell degeneration, and atrophy. In contrast to a single injection of CdMT that produces proximal tubular necrosis, chronic injection of CdMT results in tubular cell apoptosis in both wild-type and MT-null mice. These data indicate that chronic CdMT administration produces similar renal injury to that observed after chronic CdCl2 administration, and that intracellular MT protects against nephrotoxicity produced by chronic CdMT administration.

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Documento generato il 30/11/20 alle ore 07:13:46