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Osama M. Sarhan, MD1, IMAN O. SHERIF, PHD2.
1Mansoura Urology and Nephrology Center, Mansoura, Egypt, 2Mansoura University, Mansoura, Egypt.

Cisplatin is an antineoplastic agent which is widely used for the treatment of various genitourinary tumors. Although it is a very effective chemotherapy, its use is limited by its renal and testicular toxicity. Arjunolic acid, a naturally occurring chiral triterpenoid saponin present in the bark of Terminalia arjuna tree, is a new multifunctional therapeutic agent with various biological functions. Our aim was to investigate the protective role and the mechanism of action of Arjunolic acid as a possible protective agent against Cisplatin induced testicular toxicity in rats.
A total of 30 male Sprague Dawley rats were used for the experiment. They were divided into 3 groups: Group 1 served as control group, Group 2 ( Cisplatin group) received a single intraperitoneal dose of Cisplatin 7mg/kg and Group 3 (Arjunolic acid group) received Arjunolic acid 20mg/kg for 10 days with a single dose of Cisplatin 7mg/kg at day three. Testicular weight and plasma testosterone level were determined along with testicular malondialdehyde (MDA) and reduced glutathione (GSH) levels as oxidative stress markers. Testicular gene expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and mitogen activated protein kinase (MAPK) were estimated by real time-PCR. Histopathological examination for testicular tissues was also done.
Cisplatin induced a significant reduction in testicular weights, plasma testosterone and testicular GSH levels in addition to significant elevation of testicular MDA levels and gene expressions of iNOS, TNF-α and MAPK when compared with control group (p< 0.05). Histopathology showed lower tubular diameters and depletion of germ cells, irregular small seminiferous tubules with Sertoli cells only were observed in Cisplatin group. Arjunolic acid administration significantly corrected the changes in both biochemical and histopathological parameters.
Our study showed that Cisplatin treatment markedly impaired testicular function in rats through mechanisms that could be significantly salvaged with co-administration of Arjunolic acid. There is a significant role of MAPK, TNFα and iNOS in the pathogenesis of Cisplatin induced oxidative injury in rat testis. So, we suggested that Arjunolic acid may have a potential protective effect against testicular damage caused by Cisplatin. Further studies are needed to validate our findings.

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