Presentation Authors: Omri Nativ*, Igor Sukhotnik, Yoav Ben-Shahar, Hila Shefer, Jacob Bejar, Miguel Gorenberg, Haifa, Israel
Introduction: Exposure to ionizing radiation results in cytotoxic and genotoxic effects caused mainly by the oxidative damage. Germ cell epithelium is highly sensitive to radiation effect that can increase the level of apoptosis post radiation therapy. The toxicity of mis-repaired DNA damage is limited by cell death that results in sub-fertility or infertility. In the present study, we investigated the radioprotective effect of a novel nano-encapsulated antioxidant cocktail on germ cell apoptosis and spermatogenesis in rats subjected to whole body radiation (WBIR).
Methods: Adult male rats weighing 250-270 g were divided into four groups, 8 rats in each. Group 1 served as control, group 2 received an intraperitoneal (IP) single dose of antioxidant cocktail (1 ml), group 3 was exposed to a WBIR (6 Gy) and group 4 received antioxidant cocktail before WBIR (6 Gy). Rats from each group were sacrificed after 48 hours. The antioxidant cocktail is composed of different vitamins, minerals and herbal remedies that were proven in previous clinical trials to be radioprotective. Malondialdehyde (MDA) levels were measured in serum (TBARS assay) to evaluate the oxidative damage. Johnsen's criteria and the number of germinal cell layers were used to categorize spermatogenesis. TUNEL assay was used to determine germ cell apoptosis. Statistical analysis was performed using one-way ANOVA test.
Results: Total body IR resulted in histological testicular damage (decrease in Johnsen's criteria, p < 0.05) that was accompanied by a significant increase in germ cell apoptosis, expressed as the number of apoptotic cells per 100 tubules (AI-1 apoptotic index) and the number of positive tubules per 100 tubules (AI-2 apoptotic index). Treatment with antioxidant cocktail resulted in a significant decrease in germ cell apoptosis (33% decrease in AI-1, p < 0.05 and 34% decrease in AI-2, p < 0.05) that was accompanied by an improved spermatogenesis (increase in Johnsen's criteria, p < 0.05).
Conclusions: In an experimental rat model of WBIR, our novel antioxidant treatment ameliorates oxidative stress induced testicular damage, i.e. decreases germ cell apoptosis and improves spermatogenesis.