Long-term mequindox treatment induced endocrine and reproductive toxicity via oxidative stress in male Wistar rats

Journal Article · Sun May 01 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.02.020· OSTI ID:21535293

Ihsan, Awais ^[1]; Xu, Wang ^[1]; Zhaoying, Liu ^[1]; Yulian, Wang ^[1]; Xianju, Huang ^[1]; Yu, Liu; Huan, Yu; Hongfei, Zhang; Tingting, Li; Chunhui, Yang ^[1]

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1. National Reference Laboratory of Veterinary Drug Residues and MOA Key Laboratory of Food Safety Evaluation, Huazhong Agricultural University, Wuhan 430070 (China)

Mequindox (MEQ) is a synthetic antimicrobial chemical of quinoxaline 1, 4-dioxide group. This study was designed to investigate the hypothesis that MEQ exerts testicular toxicity by causing oxidative stress and steroidal gene expression profiles and determine mechanism of MEQ testicular toxicity. In this study, adult male Wistar rats were fed with MEQ for 180 days at five different doses as 0, 25, 55, 110 and 275 mg/kg, respectively. In comparison to control, superoxide dismutase (SOD), reduced glutathione (GSH) and 8-hydroxydeoxyguanosine (8-OHdG) levels were elevated at 110 and 275 mg/kg MEQ, whereas the malondialdehyde (MDA) level was slightly increase at only 275 mg/kg. Furthermore, in LC/MS-IT-TOF analysis, one metabolite 2-isoethanol 4-desoxymequindox (M11) was found in the testis. There was significant decrease in body weight, testicular weight and testosterone at 275 mg/kg, serum follicular stimulating hormone (FSH) at 110 and 275 mg/kg, while lutinizing hormone (LH) levels were elevated at 110 mg/kg. Moreover, histopathology of testis exhibited germ cell depletion, contraction of seminiferous tubules and disorganization of the tubular contents of testis. Compared with control, mRNA expression of StAR, P450scc and 17{beta}-HSD in testis was significantly decreased after exposure of 275 mg/kg MEQ while AR and 3{beta}-HSD mRNA expression were significantly elevated at the 110 mg/kg MEQ group. Taken together, our findings provide the first and direct evidence in vivo for the formation of free radicals during the MEQ metabolism through N {yields} O group reduction, which may have implications to understand the possible mechanism of male infertility related to quinoxaline derivatives.

• OSTI ID: 21535293
• Journal Information: Toxicology and Applied Pharmacology, Vol. 252, Issue 3; Other Information: DOI: 10.1016/j.taap.2011.02.020; PII: S0041-008X(11)00074-3; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADULTS
CENTRAL NERVOUS SYSTEM
CONTROL
DNA DAMAGES
DOSES
FSH
GERM CELLS
GLUTATHIONE
HYDROGEN PEROXIDE
IN VIVO
MALES
MESSENGER-RNA
METABOLISM
OXIDATION
RATS
RECEPTORS
SUPEROXIDE DISMUTASE
TESTES
TESTOSTERONE
TOXICITY
AGE GROUPS
ANDROGENS
ANDROSTANES
ANIMALS
BODY
CHEMICAL REACTIONS
DRUGS
ENZYMES
GONADOTROPINS
GONADS
HORMONES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
KETONES
MALE GENITALS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEPTIDE HORMONES
PEPTIDES
PEROXIDES
PITUITARY HORMONES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
RNA
RODENTS
STEROID HORMONES
STEROIDS
VERTEBRATES