STEN ameliorates VEGF gene expression by improving XBP1/mRNA-21/mRNA-330 signalling pathways in cisplatin-induced uterus injury in rats

Cisplatin is one of the most widely used chemotherapy treatments. It was discovered that exposure to cisplatin promotes follicular atresia of the uterus and reduces ovarian reserve. Unquestionably, strawberry is a significant source of phenolic constituents of important biological value. This study was conducted to monitor the protective effects of strawberry extract loaded within niosomes on cisplatin-induced uterine injury in rats. STEN was synthesized using the thin film hydration method and characterized using TEM, DSC, and FTIR. Also, the encapsulation efficiency was evaluated. Numerous antioxidant tests were used to assess the formulation, including those for reducing power, chelating activity on Fe²⁺, superoxide radical scavenging, singlet oxygen scavenging, and hydrogen peroxide scavenging activities. Also, the LD₅₀ of STEN given orally in adult rats was estimated, and the protective effect of STEN was studied on cisplatin-induced uterus toxicity in rats for 3 weeks. The uterus toxicity was assessed by evaluating of alters in body weight as well as uterus TBARS, CAT, SOD, GSH, TNF- α, NF-κB, IL-1β, MCP-1 and CINC-3 levels. Additionally, VEGF, XBP1, mRNA-21 and mRNA-330 gene expression in the uterus of normal and cisplatin-treated rats was evaluated. The thermogram results concluded that there is an improvement in the thermal properties of STEN. The prepared niosomal formulation showed spherical shape nanoparticles with encapsulation efficiency 72%. The IC₅₀ values of STE for superoxide radical, singlet oxygen and hydrogen peroxide scavenging activities were 39.72 μg/ml, 83.29 μg/ml and 4.14 mg/mL, respectively. In addition, The IC50 values of STEN for superoxide radical, singlet oxygen and hydrogen peroxide scavenging activities were 16.20 μg/ml, 66.01 μg/ml and 1.32 mg/mL, respectively. Furthermore, the LD₅₀ value of STEN is 1437.5 mg/kg.b.w. The administration of cisplatin resulted in decreased body weight, GSH, SOD and CAT, and IL-10 levels, as well as VEGF and mRNA-330 gene expression. Obviously, our findings revealed a significant elevation in TBARS, TNF- α, IL-1β, NF-κB, CINC-3 and MCP-1 levels as well as the expression of XBP1, mRNA-21 genes. Also, administration of STEN significantly improved body weight, GSH, SOD and CAT, IL-10, TBARS, TNF- α, IL-1β, NF-κB and MCP-1 levels in plasma and uterus tissue. On the other hand, VEGF and mRNA-330 gene expression was downregulated in uterus of STEN-treated rats. Conclusions: The findings imply that STEN could be used as a new pharmaceutical drug in the treatment of uterus toxicity.