Background: Doxorubicin (DOX) is a widely used anticancer drug, but its use in clinical chemotherapy is limited due to its side effects, including testicular toxicity. The aim of this study was to investigate the protective effect of nano-zinc oxide (nZnO) on DOX-induced reproductive toxicity in male rats.

Materials and Methods: In this experimental study, adult male Wistar rats were randomly divided into four groups, including one control and three experimental groups. They received saline, DOX (6 mg/kg), nZnO (5 mg/kg), and nZnO followed by DOX (i.p), respectively. Treatment was performed for 3 days. After 28 days, post-administration histological changes and reproductive indices were studied.

Results: Administration of DOX induced a significant reduction in seminiferous tubules diameter and thickness of germinal epithelium. Also, fertility and fecundity indices, number of litters and epididymal sperm concentration, decreased, whereas degenerated Leydig cells and deformed Sertoli cells increased.

Conclusion: Coadministration of nZnO significantly improved DOX-induced changes. These findings show the protective role of nZnO in DOX-induced reproductive toxicity.

Background: Doxorubicin is a chemotherapeutic agent still in widespread use in hematologic malignancies. A side effect of anthracyclines such as doxorubicin is the activation of nuclear factor-&kappaB (NF-&kappaB), a potent inducer of antiapoptotic genes, which may blunt the therapeutic efficacy of the drugs. In this study, the effect of indole -3-carbinol (I3C) on the activation NF-&kappaB and the anti-apoptotic genes whose expression is regulated by NF-&kappaB was assessed in NALM-6 cells.

Materials and Methods: NALM-6 cells were preincubated with various concentrations of I3C and then treated with doxorubicin. Cellular DNA content assay and Annexin V-FITC staining were performed by flowcytometry for evaluation of apoptosis. For assessing the effect of I3C on the expression of XIAP, survivin, and nuclear p65 proteins, NALM-6 cells were pretreated with I3C and then incubated with doxorubicin. Whole-cell and nuclear extracts were prepared for Western blot analysis. A paired t-test was conducted to evaluate the results.

Results: DNA histogram analysis of NALM-6 cells indicates a combination of I3C with doxorubicin significantly escalated the percentages of sub-G1 population cells compared with doxorubicin - only treated group (p<0.05). Annexin V-FITC staining also showed that cotreatment of NALM-6 cells with I3C and doxorubicin significantly increased the proportion of Annexin-V positive cells in comparison with the doxorubicin treated cells (p<0.05). The western blot analysis indicated I3C significantly inhibits both doxorubicin -induced nuclear translocation of p65 and the expression of doxorubicin-induced NF-&kappaB target.

Conclusion: Our results indicated that using natural non-toxic inhibitors of NF-&kappaB such as I3C in combination with anthracyclines might be a rational combination therapy for BCP-ALL cells in which NF-&kappaB is constitutively active.