We describe testicular changes in Wistar and Sprague-Dawley rats following oral administration of DF2156A, a novel allosteric inhibitor of the CXCR1/CXCR2 receptors of interleukin-8. These testicular changes, which were associated with clinical signs, modifications of body weight parameters (decrease of body weight and weight gain) and a decrease of testosterone serum levels, were not considered to be a direct toxic effect of the test substance but secondary to a likely induced stress resulting from the oral administration of a high dose (200 mg/kg/day) of the test substance to male rats for a period of six weeks. Testicular changes consisted of seminiferous tubules atrophy and germinal cell degeneration and only occurred in animals presenting clinical signs of transient visible weight loss, ruffled fur and/or weakened condition, and/or decreased body weight and weight gain. A decrease in serum testosterone levels was only observed in those Sprague-Dawley rats affected by decreased body weight, weight gain and testicular changes. Only a single Wistar rat with testicular changes exhibited relevant reduced levels of circulating testosterone. Sperm analysis in terms of motility, morphology and number of sperm cells was altered in males presenting with morphological changes in the testes. Sprague-Dawley rats with testicular changes were more numerous and with more pronounced lesions than were Wistar rats.
Keywords: Glucocorticoids; Sprague-Dawley rat; Stress-related; Testes; Testosterone; Wistar rat.
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