Sex differences in the excretion levels of traditional and novel urinary biomarkers of nephrotoxicity in rats.
J Toxicol Sci
; 42(5): 615-627, 2017.
Article
en En
| MEDLINE
| ID: mdl-28904297
Urinary biomarkers have been used widely in preclinical toxicity studies to detect dysfunctions and injuries of the kidney caused by drugs under development. While they have been well studied for evaluating nephrotoxicity, knowledge of sex differences in excretion levels of urinary biomarkers remains inadequate. We conducted experiments focused on effects of endogenous sex hormones on urinary biomarkers using intact and castrated male and female rats. Comparisons of the urinary biomarker excretion levels between intact male and female rats at 5, 7, 9 and 12 weeks of age revealed higher excretion levels of leucine aminopeptidase (LAP), γ-glutamyl transpeptidase (γGTP), total protein, liver-type fatty acid-binding protein (L-FABP), cystatin C (Cys-C) and ß2-microglobulin (ß2-MG), and lower excretion level of kidney injury molecule 1 (Kim-1), in male rats as compared to female rats. Orchidectomized male rats showed lower urinary excretion levels of alkaline phosphatase (ALP), LAP, γGTP, N-acetyl-ß-D-glucosaminidase (NAG), glucose, total protein, L-FABP, Cys-C, ß2-MG and neutrophil gelatinase-associated lipocalin (NGAL), and higher urinary excretion levels of clusterin (CLU) and Kim-1, than sham-operated male rats. On the other hand, no significant differences in the urinary biomarker excretion levels excluding ALP were observed between ovariectomized and sham-operated female rats. In the present study, we demonstrated the existence of sex differences in excretion levels of urinary biomarkers that are universally used in preclinical toxicity studies, and also that these differences, especially in relation to the urinary excretions of ALP, LAP, γGTP, total protein, L-FABP, Cys-C, and ß2-MG, may closely relate to the endogenous testosterone.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hormonas Esteroides Gonadales
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Testosterona
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Biomarcadores
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Pruebas de Toxicidad
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Lesión Renal Aguda
Límite:
Animals
Idioma:
En
Revista:
J Toxicol Sci
Año:
2017
Tipo del documento:
Article
Pais de publicación:
Japón