Urapidil alleviates ovarian torsion detorsion injury via regulating oxidative stress, apoptosis, autophagia, and inflammation

Abstract

Objectives: This study aimed to determine anti-inflammatory, antioxidant, and antiapoptotic properties of urapidil (Ura) against ovarian torsion detorsion (T/D) injury in rats.

Materials and methods: 40 female Wistar albino rats were grouped as sham, T/D, T/D+dimethyl sulfoxide (DMSO), T/D+Urapidil (Ura) 0.5 mg/kg (low dose), and T/D+Urapidil (Ura) 5 mg/kg (high dose) groups. In treatment groups, Ura was administered intraperitoneally just before detorsion. Biochemical parameters (TAS, TOS, MDA, MPO, and SOD) and immunohistochemical (IL-1β, TNF-α, NF-κB, LC3B, and Caspase-3) analyzes were performed.

Results: In the T/D group, OSI and MPO levels were elevated significantly while TAS values decreased compared with the sham group. A significant difference occurred in the low dose treatment group in TAS and OSI levels compared with the T/D group. In the high dose treatment group, significant elevation in TAS but reduction in OSI and MDA levels were observed compared with the T/D group. Immunohistochemical staining resulted in IL-1β, TNF-α, NF-κB, LC3B, and caspase-3 immunopositivity in the T/D group, while Ura treatment decreased those parameters. Intensive congestion and hemorrhage were observed in the T/D group, but contrary to this, treatment groups had alleviated congestion and hemorrhage.

Conclusion: These results suggest that Ura demonstrated protective effects against ovarian T/D injury via anti-oxidative, anti-inflammatory, and anti-apoptotic features.

Keywords: Autophagy; Caspase-3; Detorsion; NF-κB; Ovarian; Torsion; Urapidil.

Figure 1

Histopathological images of rat ovarian tissue samples (H&E, ×20 magnification). a) Sham group demonstrated normal ovarian histological structure. b) T/D and c) T/D+DMSO groups’ I/R tissue samples with ovarian sections containing severe hemorrhage (arrows) in rats. d) T/D+Ura 0.5 mg/kg and e) T/D+Ura 5 mg/kg groups’ I/R and Ura-treated samples; ovarian sections containing mild hemorrhage and hyperemia (arrows). DMSO: Dimethyl sulfoxide; Ura: Urapidil; T/D: Torsion detorsion

Figure 2

Representative images of the effect of Ura treatment after ovarian T/D injury (x20, IHC): Arrows show IL-1β immune positive cells. a) sham group with negative IL-1β immunopositivity of the lutein and interstitial cells. b) T/D group with intense IL-1β immunopositivity of lutein and interstitial cells. c) T/D+DMSO group with more intense IL-1β immunopositivity of lutein and interstitial cells. d) T/D+Ura 0.5 mg/kg group with moderate IL-1β immunopositivity of lutein and interstitial cells. e) T/D+Ura 5 mg/kg group with mild IL-1β immunopositivity of lutein and interstitial cells

Figure 3

Representative images of the effect of Ura treatment after ovarian T/D injury (x20, IHC): Arrows show TNF-α immune positive cells. a) sham group with negative TNF-α immunopositivity of lutein and interstitial cells. b) T/D group with more intense TNF-α immunopositivity of lutein and interstitial cells. c) T/D+DMSO group with intense TNF-α immunopositivity of the interstitial cells. d) T/D +Ura 0.5 mg/kg group with mild TNF-α immunopositivity of the lutein cells. (e) T/D +Ura 5 mg/kg group with mild IL-1β immunopositivity of the interstitial cells

Figure 4

Representative images of the effect of Ura treatment after ovarian T/D injury (x20, IHC): Arrows show NF-κB immune positive cells. a) sham group with negative NF-κB immunopositivity of lutein and interstitial cells. b) T/D group with intense TNF-α immunopositivity of the lutein cells. c) T/D+DMSO group with more intense NF-κB immunopositivity of lutein and interstitial cells. d) T/D +Ura 0.5 mg/kg group with moderate NF-κB immunopositivity of lutein and interstitial cells. e) T/D +Ura 5 mg/kg group with mild NF-κB immunopositivity of the lutein cells

Figure 5

Representative images of the effect of Ura treatment after ovarian T/D injury (x20, IHC): Arrows show caspase-3 immune positive cells. a) sham group with negative caspase-3 immunopositivity of the lutein cells. b) T/D group with intense caspase-3 immunopositivity of the lutein cells. c) T/D+DMSO group with more intense caspase-3 immunopositivity of lutein and interstitial cells. d) T/D +Ura 0.5 mg/kg group with intense caspase-3 immunopositivity of lutein and interstitial cells. e) T/D +Ura 5 mg/kg group with mild caspase-3 immunopositivity of the interstitial cells

Figure 6

Representative images of the effect of UR treatment after ovarian torsion detorsion injury (x20, IHC): Arrows show LC3B immune positive cells. (a) sham group with negative LC3B immunopositivity of lutein and interstitial cells. (b) T/D group with intense LC3B immunopositivity of lutein and interstitial cells. (c) T/D+DMSO group with intense LC3B immunopositivity of the lutein cells. (d) T/D +Ura 0.5 mg/kg group with intense LC3B immunopositivity of lutein and interstitial cells. (e) T/D +Ura 5 mg/kg group with mild IL-1β immunopositivity of the interstitial cells