Lycopene protects against Bisphenol A induced toxicity on the submandibular salivary glands via the upregulation of PPAR-γ and modulation of Wnt/ß-catenin signaling.

ABSTRACT

BACKGROUND AND AIM: The submandibular salivary glands (SMG) represent a suitable model for studying epithelial cell growth and differentiation. Bisphenol A (BPA) is a xenoestrogen, synthesized to produce polymers such as polycarbonates and epoxy resins. There are concerns about the occurrence of BPA in food, water as well as its appearance in human tissues and body fluids. Lycopene (LYC) is a carotenoid compound that exerts antioxidant and anti-inflammatory properties. This work was performed to study possible protective effect of LYC against BPA toxicity in SMG. MATERIAL AND METHODS: 40 albino rats were divided into 4 groups; Group I served as controls. Group II rats received LYC (4 mg/kg, p.o), Group III rats received BPA (10 mg/kg, p.o) and Group IV rats received LYC (4 mg/kg, p.o) and BPA (10 mg/kg, p.o). All drugs were administered for 45 days then under anesthesia, rats were sacrificed. The SMG specimens were taken for histological and biochemical studies. RESULTS: BPA resulted in a significant rise of malondialdehyde, tumor necrosis factor-α and interleukine-1ß. In contrast, the tissue levels of glutathione and PPAR-γ were significantly decreased. BPA activated Wnt/ß-catenin pathway evidenced by upregulating WNT3a, ß-catenin and c-myc expression. Moreover, SMG of BPA showed degenerative changes that affected the parenchymal and stromal elements of the glands. The immunohistochemical localization of cytokeratin 5,6 and 18 of BPA rats revealed weak immunostaining of the serous secretory cells, myoepithelial cells and ductal cells. Upon treatment with LYC, glutathione and PPAR-γ were restored. CONCLUSION: LYC acted as a protective agent against BPA-induced pathological changes in SMG.