Exploring porcine kidney explants as a model for the study of nephrotoxins and the therapeutic potential of phytic acid.

The use of in vivo models to assess nephrotoxicity has faced ethical limitations. A viable alternative is the ex vivo model that combines the 3 R principles with the preservation of tissue histology. Here, we established a gentamicin nephrotoxicity model using pigs` kidney explants and investigated the effect of phytic acid (IP6) against gentamicin- induced nephrotoxicity. A total of 360 kidney explants were divided into control, gentamicin (10 mM), IP6 (5 mM), and gentamicin+IP6 groups. The activity of gammaglutamyltransferase (GGT), creatinine levels, histological assessment, oxidative stress, and inflammatory cytokine expression were analyzed. Exposure to gentamicin induced an increase in GGT activity, creatinine levels, lesion score, lipoperoxidation and IL-8 expression. Explants exposed to IP6 remained like the control. The addition of IP6 to gentamicin prevented tissue damage, increasing the antioxidant status and gene expression of IL-10. This model proved to be an adequate experimental approach for identifying nephrotoxins and potential products to modulate the toxicity.

Impairment of postnatal epididymal development and immune microenvironment following administration of low doses of malathion during juvenile and peripubertal periods of rats.

Malathion is an organophosphate pesticide widely used for agricultural crops and for vector control of Aedes aegypti. Humans are exposed to this environmental contaminant by ingesting contaminated food. The juvenile and peripubertal periods are critical for the postnatal development of the epididymis and are when animals are most vulnerable to toxic agents. Since juveniles and adolescents are developing under exposure to the insecticide malathion, the aim of the present study was to evaluate the effects of exposure to low doses of malathion on postnatal epididymal development in rats. Male Wistar rats were exposed to malathion daily via gavage at doses of 10 mg kg-1 (M10 group) or 50 mg kg-1 (M50 group) for 40 days (postnatal days (PNDs) 25-65). The control group received the vehicle (0.9% saline) under the same conditions. On PND 40, the epididymides were removed, weighed and used for histological analysis and determination of the inflammatory profile and sperm count. Sperm from the vas deferens were subjected to sperm motility analysis. The M50 group showed tissue remodelling in the caput and cauda epididymides and increased neutrophil and macrophage migration in the caput epididymis. The M10 group showed decreased motile spermatozoa and IL-6 levels in the caput epididymis. Both doses decreased the IL-1ß level and altered the morphology of the same region. These results show that malathion exposure may impair postnatal epididymal development. Furthermore, alterations of the immune system in the epididymal environment are presented as new findings regarding the action of malathion on the epididymis.