Effects of lonidamine on testicular and epididymal proteins in the rat

Citation
Mg. Leone et al., Effects of lonidamine on testicular and epididymal proteins in the rat, REPROD TOX, 14(3), 2000, pp. 257-263
Citations number
37
Categorie Soggetti
da verificare
Journal title
REPRODUCTIVE TOXICOLOGY
ISSN journal
08906238 → ACNP
Volume
14
Issue
3
Year of publication
2000
Pages
257 - 263
Database
ISI
SICI code
0890-6238(200005/06)14:3<257:EOLOTA>2.0.ZU;2-Q
Abstract
The mechanism responsible for the antispermatogenic activity of lonidamine (LND) [1-(2,4-dichlorobenzy1)-1H-indazole-3-carboxylic acid], a drug with l ow systemic toxicity and lack of significant hormonal effects, is still unc lear but may be related to alterations of Sertoli cell proteins. Here, we c onfirmed that a single oral dose of LND (100 mg/kg b.w.) to sexually mature Sprague-Dawley rats causes shrinkage and weight reduction of the testes af ter 48 h. These macroscopic changes correlated with histologic alterations revealed by light microscopy, consistent with partially reversible inhibiti on of spermatogenesis. When the testes and the epididymides of animals trea ted with or without LND were homogenized and analyzed by the Bradford assay , a significant increase of total protein content was observed after 24 and 48 h. When these homogenates were analyzed by concanavalin blotting, speci fic changes of the major rat macroglobulins, i.e. alpha(1)-inhibitor-3, alp ha(2)-macroglobulin, and alpha(1)-macroglobulin, were noted. In particular, LND caused a decrease of testicular alpha(1)-inhibitor-3, but not an incre ase of testicular alpha(2)-macroglobulin, indicating a mild local inflammat ory response to the drug. (C) 2000 Elsevier Science Inc. All rights reserve d.