Protective effect of astaxanthin against SnS2 nanoflowers induced testes toxicity by suppressing RIPK1-RIPK3-MLKL signaling in mice.

Abstract The reproductive toxicity of SnS2 nanoflowers (SnS2 NFs) has been studied in our previous experiment, but the underlying mechanism is still not clear. Astaxanthin (ASX) is a red carotenoid pigment with antioxidant, anticancer and anti-inflammatory properties, showing neuroprotective properties via its antioxidant capacity. To examine the ASX effect on sub-chronic testis injury induced by SnS2 NFs, we randomly and equally divided 40 Kunming male mice into four groups (control, ASX control, NF and NF+ASX groups). Then, ASX dissolved in olive oil was administered intragastrically for 30 consecutive days. Results showed that ASX treatment improved the sperm parameters in mice. Meanwhile, the ASX treatment significantly attenuated testis histopathological injury and ultrastructure alterations induced by SnS2 NFs. It also alleviated testicular oxidative stress, inflammation, apoptosis and necroptosis in mice. Furthermore, ASX markedly upregulated the expression of Bcl-2 and downregulated the expressions of Fas, FasL, RIPK1, FADD, Bax, Cytochrome C, Caspase-9, Cleaved Caspase-8, Cleaved Caspase-3, RIPK3, MLKL and FLIP in the testis tissues compared with the NF group. Therefore, ASX had a markedly protective effect against SnS2 NFs in mice, and the potential mechanism is associated with its ability to inhibit the oxidative stress, inflammatory response, testicular apoptosis and necroptosis, as well as downregulating in the expression of the RIPK1-RIPK3-MLKL signaling and mitochondrial related apoptosis genes.