Morin hydrate alleviated cisplatin-induced testicular toxicity in rats via modulating NLRP3/NF-κB pathway

Abstract

Cisplatin (Cis) has been widely used for treating many types of solid tumors. Despite its clinical effectiveness, Cis has a considerable risk of gonadal damage that may cause infertility. Morin hydrate (MH), a natural bioflavonoid, has been known for its antioxidant and anti-inflammatory effects. Our study aimed to investigate whether pretreatment with MH could protect against Cis-induced testicular toxicity. Thirty-five adult male rats were split into five groups ( n = 7, each); control group received oral 0.5% CMC for 10 days, MH group received oral MH (100 mg/kg) for 10 days, Cis group was given a single dose of Cis (7 mg/kg, i.p) on day 5, (MH 50 + Cis) and (MH 100 + Cis) groups were pretreated with MH (50 mg/kg) and (100 mg/kg), respectively for 5 days before Cis administration, and then, treatment was continued, with either doses, for further 5 days. At the end of the study, blood and testicular tissues were collected for biochemical and histopathological studies. MH administration mitigated the testicular histopathological changes induced by Cis, increased sperm count and motility, and abrogated the abnormalities in sperm morphology. Further, MH enhanced antioxidant status and suppressed the inflammation via downregulating NF-κB and NLRP3 and inflammatory cytokines expression. Our in vitro study revealed that MH enhanced Cis-induced cytotoxicity against cancer cells, including PC3, MCF7, and HepG2. These findings suggested that MH could be applied in Cis chemotherapy regimens as a possible adjuvant therapy to enhance its effect and prevent Cis-induced testicular damage. Graphical Abstract

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