Squid ink polysaccharide reduces cyclophosphamide-induced testicular damage via Nrf2/ARE activation pathway in mice

Cyclophosphamide (CP) toxicity on testis was hampered by squid ink polysaccharide (SIP) via restoration of antioxidant ability in our previous investigations. This study investigated roles of Nrf2/ARE signal pathway in testis of treated mice. Male Kunming mice were employed to undergo treatment with SIP and/or CP. Protein levels of Nrf2, keap-1, histone deacetylase 2 (HDAC2), quinone oxidoreductase 1 (NQO-1), and heme oxygenase 1 (HO-1) and phosphorylation level of protein kinase C (PKC) in testis were evaluated by Western blotting. Data showed that SIP elevated expressions of NQO-1 and HO-1 genes, two downstream target molecules of Nrf2, via activating Nrf2 to play preventive roles on CP-treated testis, and further discovered that upstream regulators of Nrf2, keap-1, HDAC2, and PKC, were concerned with the regulation of Nrf2. These results suggest that SIP could effectively weaken CP-associated testicular damage via Nrf2/ARE signal pathway.