Mitigation of testicular damage induced by DMBA/TPA through Murraya koenigii (L.) Spreng.: Insights into antioxidant and anti-apoptotic mechanisms

Abstract

Abstract BACKGROUND: 7,12-Dimethylbenz[a]anthracene (DMBA) is a known mutagen, teratogen, and toxicant besides being a significant factor responsible for skin carcinogenesis. During carcinogenesis, DMBA and its metabolites produce excessive free radicals and oxidative stress. This oxidative stress further targets various cell organelles. Consequences of the damage by DMBA also influence vital organs, such as the brain, liver, and testis, with complex reactions, such as an increase in mutation, modification in cell membranes, structural proteins, metabolic enzymes, and signaling proteins. Therefore, this study evaluated the possible role of hydroethanolic Murraya koenigii (L.) Spreng. leaves extract (HEMKLE) upon damages incurred in testis tissues against DMBA/12-O-tetradecanoyl phorbol-13-acetate (TPA) in skin tumor-bearing mice. METHODS: Forty male LACA mice were segregated into four groups: control, DMBA/TPA, HEMKLE, and HEMKLE + DMBA/TPA. Skin tumors were induced by DMBA (500 nmol/100 μL of acetone) and TPA (1.7 nmol/100 μL of acetone; applied topically). RESULTS: The protective response of HEMKLE (200 mg/kg body weight) to testicular damage during skin tumorigenesis was apparent by recovery of endogenous antioxidant enzymes, along with histoarchitecture in the HEMKLE + DMBA/TPA group contrasted with the DMBA/TPA group. Furthermore, in the HEMKLE + DMBA/TPA group, reduced messenger ribonucleic acid and protein expressions of proapoptotic genes (caspase-9 and caspase-3) and enhancement in Bcl-2 were observed, proposing the anti-apoptotic potential of HEMKLE in testicular tissues. CONCLUSION: HEMKLE could be used as a nutraceutical or antioxidant drug to protect the body from testicular insults.