Abstract
Breast cancer remains a global health burden, and the need for effective therapies is of chief importance. The current study explored the in vivo chemoprotective activity of palmitoylethanolamide (PEA) against 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast tumor in rats. Results of noninvasive photoacoustic imaging showed real-time progression in the tumor area and volume in DMBA-induced rats, while there was a reduction in tumor area and volume in PEA-treated tumor-bearing rats. The increase in the average oxygen saturation (sO2 %) and decrease in the average total hemoglobin (HbT %) indicated the PEA-mediated attenuation of hypoxia-induced neovascularization in DMBA-induced rats. Histopathological investigations confirmed the efficacy of PEA in mitigating breast carcinoma, hepatotoxicity and nephrotoxicity driven by DMBA. Moreover, PEA-mediated alterations in the metabolic activity of the tumor microenvironment were evidenced by decreased glucose and lactate dehydrogenase enzyme level in the blood plasma and mammary tissue. PEA also maintained the redox balance by inhibiting nitric oxide level, reducing malondialdehyde (a product of lipid peroxidation), and increasing the level of antioxidant enzyme reduced glutathione. PEA altered the expression of apoptosis-related genes (BAX, P53,BCL-XL, CASPASE-8, and CASPASE-9) and induced the activity of Caspase-3 protein in the mammary tissue of tumor-bearing rats, indicating its apoptosis inducing ability. Taken together, the findings of this study suggest that PEA may have a protective effect against DMBA-induced breast tumors.