Morin hydrate treatment minimizes Di(2-ethylhexyl) phthalate-induced uterine fibrosis, oxidative stress, and apoptosis in mice.

BACKGROUND

Di (2-ethylhexyl) phthalate (DEHP), a widely used chemical in plastics, has various health hazards when accumulated in the environment. DEHP has been shown to cause toxicity to various organs like the liver, kidney, and reproductive organs. Phytocompounds have been used to mitigate DEHP-mediated organ toxicity. Morin hydrate (MH), a phytocompound, has also been known to protect tissue and organs against various induced toxic conditions. However, the impact of MH treatment on DEHP-induced uterine dysfunction has not yet been still investigated. Therefore, the present study has investigated the impact of MH on uterine physiology and morphology of DEHP-intoxicated mice.

METHODS

Twenty Swiss mice were randomly divided into four groups (n = 5): control (CN), Di (2-ethylhexyl) phthalate (DP) (500 mg/kg), Di (2-ethylhexyl) phthalate (DP) + Morin hydrate (MH) (10 mg/kg), and Di (2-ethylhexyl) phthalate (DP) + Morin hydrate (MH) (100 mg/kg) for 14 days.

RESULTS

Our results showed that the expression of active caspase-3 was up-regulated, and Bcl2 was down-regulated in the uterus of DEHP-treated mice. Furthermore, the uterine histology also showed decreased luminal epithelium height and endometrium thickness in the DEHP-treated mice; however, myometrium layer (outer and inner) thickness was higher in DEHP-treated mice. The uterus of DEHP-treated mice also exhibited elevated oxidative stress and fibrosis, along with decreased estrogen levels and expression of estrogen receptors (ERs). MH treatment at both doses (10 and 100 mg/kg) suppressed DEHP-induced uterine apoptosis (increased Bcl2 and decreased active caspase-3 expression) and fibrosis. MH also increased the circulating estrogen levels at both doses; Further ERα and ERβ expression were elevated in the MH treated in both groups). The levels of oxidative stress malondialdehyde (MDA levels) were higher in the uterus of DEHP alone and DEHP plus MH-treated mice (100 mg/kg). Moreover, the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase (Gpx and SOD) did not show a dose-dependent response to MH treatment; rather, MH showed a differential effect on these enzymes. The elevated oxidative stress in 100 mg/kg MH treated uterus, despite elevated Gpx and SOD, remains unclear. Thus, these results suggest that MH ameliorates DEHP-induced uterine fibrosis, apoptosis, and histoarchitecture through ER modulation.

CONCLUSION

These findings suggest that MH improves uterine structure and function in DEHP-treated mice.