Ameliorative effect of fractionated low-dose gamma radiation in combination with ellagic acid on nicotine-induced hormonal changes and testicular toxicity in rats

Nicotine is an active pharmacological ingredient in cigarette smoke, which may negatively influence the male reproductive system and fertility. This study aims to investigate the effect of fractionated low-dose radiation (fractionated-LDR) and/or ellagic acid (EA) on nicotine-induced hormonal changes and testicular toxicity in rats. Nicotine was administrated orally (1 mg/kg) for 30 days, afterward, rats were treated with LDR (2 × 0.25 Gy/1-week interval), EA (10 mg/kg, 14 consecutive days p.o.), or a combination of both fractionated-LDR and EA. Rats were sacrificed 24 h after the last dose of treatment, then testes were dissected for histopathology examination, along with some biochemical parameters in serum and testicular tissue were evaluated. Nicotine-induced oxidative stress was evidenced by an increase in testicular thiobarbituric acid reactive substances (TBARS) and a decrease in reduced glutathione (GSH) content. Additionally, the activities of testicular androgenic enzymes were decreased, and the activity of serum lactate dehydrogenase (LDH) was significantly increased. The hormonal changes were verified by a noticeable reduction in follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone serum levels. Histological evaluation revealed that the testicular seminiferous tubules structure was distorted. On the contrary, fractionated-LDR plus EA attenuated the negative changes caused by nicotine observed through biochemical and histological findings. Accordingly, the exposure to fractionated-LDR combined with EA may be a promising candidate for treating hormonal changes and testicular toxicity caused by nicotine.