Cyclopiazonic acid induces apoptosis and oxidative stress in the testis of mice

Introduction: Mycotoxins are secondary metabolites that exhibit pharmacologic and some toxic effects in humans and animals. Among others, Cyclopiazonic acid (CPA), which is found in various foodstuffs, has cellular and molecular effects including: effects on intracellular calcium concentration and cellular sustainability and viability. In the light of mentioned properties, this study was aimed to investigate the potential effects of CPA at different doses on apoptosis induction and oxidative stress status in the testis.Methods: Forty adult male mice were randomly divided into 5 groups (n=8). The control group did not receive any treatment, while the control-sham, animals received daily 0.05% DMSO (as the CPA solvent) intraperitoneally (i.p.). In the third, fourth and fifth groups, animals received 0.3, 0.6 and 0.12 mg/kg, BW of CPA (i.p.), respectively for 28 days. Twenty-four hours after the last treatment, the testes specimen were separated and weighed. The rate of lipid peroxidation (malondialdehyde content, MDA), total thiol molecules (GSH), total antioxidant capacity (TAC) were determined. Finally, any changes in the expression of apoptotic genes (P53, Bcl-2 and Caspase 3) at mRNA level were evaluated by qPCR technique.Results: A moderate but significant (p<0.05) increase in the level of MDA content and reduction of total antioxidant capacity (TAC) in testicular tissue was observed in the animals which received the highest dose of CPA. The amount of total thiol molecules (TTM) showed a significant decrease in the CPA –exposed groups. A significant up-regulation (p<0.05) in the expression of P53 and Caspase-3 genes and down regulation (p<0.05) in the expression of Bcl-2 gene was obtained in the CPA- received groups.Conclusion: our data suggest that the reproductive toxicity of CPA partly attribute to the alterations in antioxidant imbalance and apoptosis induction.

کلیدواژه ها:

Apoptosis ، Cyclopiazonic Acid ، Mice ، Mycotoxin ، Oxidative stress