Protective Effect of Rosmarinic Acid Against Cisplatin-Induced Testicular Damage in Mice via Modulation of Inflammation, Oxidative Stress, and Apoptosis and Restoration of Nrf2/HO-1
DOI:
https://doi.org/10.51152/jbarbiomed.v11i1.255Keywords:
Testicular damage, Rosmarinic acid, Antioxidants, Inflammation, Cisplatin, Nrf2Abstract
Cisplatin (CIS) is a promising chemotherapeutic drug widely utilized for the treatment of several malignancies though its role in inducing testicular injury is established. Rosmarinic acid (RA) is a polyphenolic whose health benefits are quite well known. This research explored the ability of RA to protect against CIS-induced testicular damage and the different mechanisms involved in this protective role. For this purpose, different groups of mice were given oral doses of RA (25 and 50 mg/kg/day) for two weeks and a single dose of CIS (7mg/Kg) intraperitoneally on the 8th day. CIS administration was found to cause a considerable reduction in sperm parameters like sperm count, viability and motility. It also mediated considerable histopathological changes in parallel to augmented MDA content and reduced GSH content and CAT and SOD activities in testis. Administration of RA in tissues with CIS-induced damage caused attenuation of sperm parameter alterations, indicating protection from testicular damage. RA administration was also found to alleviate NO and MDA levels and antioxidants in mice treated with CIS. An increment in NF-κB 65, TNF-α, IL-1β, Bax and caspase-3 was caused by CIS administration which also reduced Bcl-2 levels in testis. However, RA administration caused suppression of upregulation of NF-κB and concentrations of pro-inflammatory cytokines together with alleviation of apoptosis in testis. This resulted in the improvement of all sperm parameters. The protective efficacy of RA against CIS-induced testicular damage is quite clear from these results; however, further research in this connection is still required to strengthen the basis for the development of an RA-based therapeutic tool against CIS-induced testicular damage.
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