Abstract
Effects of lonidamine on testicular and epididymal proteins in the rat
Leone,Maria Grazia; Grippa,Eleanora; Guidolin,Diego; Tita,Beatrice; Abdel-Haq,Hanin; Gatto,Maria Teresa; Bordi,Federica; Cheng,Chuen-yan; Silvestrini,Bruno; Saso,Luciano
Reproductive Toxicology 14(3): 257-263
Publication date: 2000
The mechanism responsible for the antispermatogenic activity of lonidamine (LND) [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid], a drug with low systemic toxicity and lack of significant hormonal effects, is still unclear but may be related to alterations of Sertoli cell proteins. Here, we confirmed 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 after 48 h. These macroscopic changes correlated with histologic alterations revealed by light microscopy, consistent with partially reversible inhibition of spermatogenesis. When the testes and the epididymides of animals treated 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, specific changes of the major rat macroglobulins, i.e. a-inhibitor-3, a-macroglobulin, and a-macroglobulin, were noted. In particular, LND caused a decrease of testicular a-inhibitor-3, but not an increase of testicular a-macroglobulin, indicating a mild local inflammatory response to the drug.
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