Sex-related variations in bone microstructure of rabbits intramuscularly exposed to patulin

Background: Patulin, a toxic mold metabolite, has been found as natural contaminant of processed fruits, most notably apples, apple juices and other apple-based products. A number of adverse health effects in humans and animals are associated with patulin intoxication. The current study was performed to analyse possible toxic effects of patulin on femoral bone microstructure in adult rabbits in detail. Fourteen clinically healthy four-month-old rabbits of both sexes (6 males and 8 females) were included in the study. Animals from the experimental groups (group E male, n = 3; group E female, n = 4) were injected intramuscularly with patulin at dose 10 mu g/kg body weight two times a week for 28 days. The dose of patulin was estimated based on the maximum permitted level of patulin for apple products intended for infants and young children. Three males and four females without patulin administration served as controls (groups C male and C female). Cortical bone thickness and qualitative and quantitative histological characteristics of compact bone tissue were investigated. Results: Intramuscular applications of patulin significantly increased the thickness of cortical bone in both sexes of rabbits. In patulin-exposed males, an absence of primary vascular longitudinal bone tissue near the endosteal border was observed, which could be associated with intensive bone remodeling. Femoral diaphyses of females displayed a lower number of secondary osteons in the middle part of the substantia compacta, and occurrence of the osteons near the periosteum. This could indicate alterations in bone turnover. Histomorphometrical evaluations showed significantly increased sizes of the primary osteons' vascular canals (P < 0.05) in males exposed to patulin possibly due to mycotoxin-induced increased levels of testosterone. Conclusions: This study demonstrates significant impact of intramuscular application of patulin on bone microstructure in adult rabbits. Moreover, we have found that the effects of patulin on qualitative and quantitative histological characteristics of compact bone are sex-dependent.