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Titolo:
Acute CdMT injection is not a good model to study chronic Cd nephropathy: Comparison of chronic CdCl2 and CdMT exposure with acute CdMT injection in rats
Autore:
Liu, J; Habeebu, SS; Liu, YP; Klaassen, CD;
Indirizzi:
Univcupatas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Ctr Environm & Oc Univ Kansas Kansas City KS USA 66160 xicol & Therapeut, Ctr Environm & Oc
Titolo Testata:
TOXICOLOGY AND APPLIED PHARMACOLOGY
fascicolo: 1, volume: 153, anno: 1998,
pagine: 48 - 58
SICI:
0041-008X(199811)153:1<48:ACIINA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROXIMAL CONVOLUTED TUBULES; CADMIUM-METALLOTHIONEIN; OVARIECTOMIZED RATS; IN-VITRO; NEPHROTOXICITY; KIDNEY; CHLORIDE; CELLS; TOXICITY; INJURY;
Keywords:
cadmium exposure; acute CdMT injection; nephrotoxicity; proteinuria; glucosuria; enzymuria; tubular cell necrosis; apoptosis; tubular cell atrophy; regeneration; glomerular damage; interstitial nephritis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Klaassen, CD Univcupatas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, CtrEnvironm & Oc Univ Kansas Kansas City KS USA 66160 peut, Ctr Environm & Oc
Citazione:
J. Liu et al., "Acute CdMT injection is not a good model to study chronic Cd nephropathy: Comparison of chronic CdCl2 and CdMT exposure with acute CdMT injection in rats", TOX APPL PH, 153(1), 1998, pp. 48-58

Abstract

Kidney is the main target organ of Cd toxicity in humans. Cd-induced nephrotoxicity is thought to be caused by the Cd-metallothionein complex (CdMT) that "leaks" out of the liver and is taken up by the kidney. A single injection of CdMT has therefore been used as a model to study Cd nephropathy forthe last 20 years. However, our recent studies reveal discrepancies between renal Cd concentration and nephrotoxic potencies of CdCl2 and CdMT. This study was further designed to critically evaluate whether a single injection of CdMT is an appropriate model to study the mechanism of chronic CdCl2 nephropathy. Age-matched rats were given multiple sc injections of either CdCl2 (0.8 and 1.2 mg Cd/kg) or CdMT (0.05 mg Cd/kg) daily, 6 days/week for 6weeks, or a single injection of CdMT (0.2-0.6 mg Cd/kg ip for 24 h), and the nephrotoxicity was compared. Histologically, chronic CdCl2 or CdMT administration produced damage to the whole kidney, including tubular cell degeneration, apoptosis, and atrophy; interstitial inflammation; glomerular swelling; and sclerosis. In contrast, acute CdMT injection produced severe proximal tubule necrosis as the major feature of its toxicity. Biochemically, chronic exposure to Cd produced polyuria and calciuria, while proteinuria, glucosuria, and enzymuria were mild (2-5x). In contrast, acute CdMT nephrotoxicity was characterized by marked increases in urinary protein (13x), glucose (25x), N-acetyl-beta-D-glucosaminidase (28x), lactate dehydrogenase (100x), and gamma-glutamyltranspeptidase (160x). Serum levels of creatinine and blood urea nitrogen were unchanged following chronic Cd exposure but weremarkedly elevated (5x) after acute injection of CdMT. Chronic exposure to either CdCl2 or CdMT produced nephrotoxicity at renal Cd concentration of 85 to 110 mu g/g kidney, while acute CdMT injection produced nephrotoxicity at only 5 to 7 mu g/g kidney. In conclusion, the present study indicates that the features and mechanisms of renal injury from chronic Cd exposure arequite different from those produced by a single injection of CdMT. Therefore, it is proposed that acute CdMT injection is not an appropriate model for the study of chronic Cd-induced nephrotoxicity. (C) 1998 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 15:19:28