Evaluation of the protective effects of gossypin for ischemia/reperfusion injury in ovary tissue

Abstract

Aim Ovarian ischemia–reperfusion (I/R) injury is a serious gynecological condition that affects women of reproductive age and reduces ovarian reserve. Management of I/R injury with detorsion causes reperfusion damage, in which oxidative stress plays a central role. This study aimed to investigate whether the gossypin (GOS) with antioxidant properties, a flavonoid, has beneficial effects on the biochemical, molecular, and histopathological aspects of ovarian I/R injury. Methods Thirty‐three female Balb/c mice were randomly divided into five groups as follows: Healthy (Sham‐operated control group), I/R (IR group), I/R + GOS 5 (I/R with GOS 5 mg/kg), I/R + GOS 10 (I/R with GOS 10 mg/kg), and I/R + GOS 20 (I/R with GOS 20 mg/kg). This was followed by 3 h of ischemia and subsequent reperfusion for 3 h after detorsion was exposed. GOS was injected 2 h before reperfusion. Results IL‐1β, IL‐6, TNF‐α, NF‐κB, and CASP‐3 mRNA expressions, SOD (superoxide dismutase) activity, GSH (glutathione), and MDA (malondialdehyde) levels, and histopathological changes were evaluated in ovarian tissue. Histological examination indicated that treatment of ovarian I/R injury with GOS led to the improvement of ovarian tissue, which was accompanied by an increase in SOD activity and GSH level and a decrease in MDA level, NF‐κB, TNF‐α, IL‐1β, and IL‐6 expressions. GOS was also corrected by reducing the elevated expression of CASP‐3 as apoptosis‐change marker. Conclusion These findings indicate that the treatment of GOS may be useful as a conservative approach to reverse I/R injury via amelioration of oxidative stress parameters and histopathological scores, attenuation of inflammation, and the suppression of apoptosis.

Zingiberene attenuates paclitaxel-induced ototoxicity by strengthening cochlear antioxidant defense system in vivo

“…The co-administration of PCX with many other antineoplastic drugs, including cisplatin, whose toxic effects have been well-documented, is the main cause of the ototoxic impact of PCX being obscured. As a result, functional abnormalities in the auditory system occurring during or after anticancer therapy were almost always attributed to other ototoxic drugs in combination except for PCX [3,17]. According to the mechanism of PCX, a microtubule stabilizing agent, it attaches to the b portion of microtubules to prevent depolarization and diminish axonal transmission.…”

“…The pulverized tissues were then homogenized in 1 mL of phosphate-buffered saline (PBS) homogenate buffer. Malondialdehyde (MDA) and glutathione (GSH) levels, as previously indicated in the literature respectively [5,17,22] from the supernatant generated by centrifuging of homogenized tissues, were evaluated in an ELISA reader. The data was depicted in the form of a mean and standard deviation.…”

Gossypin: A flavonoid with diverse pharmacological effects

“…According to Li Wang et al's study, gossypin induces endogenous apoptosis in both anchor‐dependent and non‐dependent gastric cancer cells, causing cysteine protease and PARP activation and cytochrome c levels to increase. When gossypin is added to the ischemia–reperfusion model (Akaras, 2019; Dincer et al, 2021), which can effectively reduce NF‐κB and CASP‐3 mRNA expression. After MTX induction in mice (Viswanatha et al, 2018), Bax gene and caspase‐3 expression increased, and the addition of gossypin can effectively inhibit the occurrence of this phenomenon.…”

“…Changes in lipid peroxidation levels can be used to measure cell membrane damage as well as changes in cell membrane structure and function. According to relevant data reports, when the concentration of gossypin reaches 37 μg/mL and 43 μg/mL, 50% in vitro lipid peroxidation can be induced by Fe 3+ /ADP ascorbic acid system and Fe 2+ /ascorbic acid system, respectively (Babu et al, 2003), for example, after the addition of gossypin, there is a significant inhibitory effect on the lipid peroxidation caused by Fe 2+ and ascorbic acid in the brain homogenate of rats (Yoon et al, 2004), Malondialdehyde (MDA) stands for oxidative damage to cells, and the addition of gossypin can improve the MDA elevation of lung tissue in mice and sepsis rats induced by MTX, and can also improve lipid peridation caused by ischemia and reperfusion of ovarian tissue, so that the level of lipid peroxidation marker MDA is reduced (Dincer et al, 2021). After exposure to lead combined with the administration of gossypin (Gautam & Flora, 2010), there is a good response to Thiobarbituric acid reactive substances (TBARS) levels.…”

“…Molecular formula: C 21 H 20 O 13 , molecular weight: 480.38, melting point: 229–230°C, boiling point: 886.0 ± 65.0°C, density 1.883 ± 0.06 g/cm 3 , and acidity coefficient (pKa): 5.70 ± 0.40. From the perspective of in vitro, gossypin has antioxidant (Ainsworth & Gillespie, 2007; Babu et al, 2003; Chandrashekhar et al, 2013; Choi et al, 2007; Cinar et al, 2019, 2022; Conforti & Menichini, 2011; Dincer et al, 2021; Gautam & Flora, 2010; Gong et al, 2022; Katary & Salahuddin, 2017; Kunnumakkara et al, 2007; Mervat & Kamal, 2021; Urarte et al, 2014; Viswanatha et al, 2018, 2019; Yoon et al, 2004), anti‐inflammatory (Akaras, 2019; Cinar et al, 2019; Mervat & Kamal, 2021; Sreeja et al, 2018), neuroprotective effect (Fernandez et al, 2009; Gautam & Flora, 2010; Viswanatha et al, 2016, 2017; Yoon et al, 2004), anti‐cancer, anti‐tumor (Bhaskaran et al, 2013; Cinar, 2020; Kunnumakkara et al, 2007; Shi et al, 2012; Wang, Zhang, et al, 2019), anti‐diabetic, (Chen et al, 2007; Venkatesan & Pillai, 2012) and other effects. This paper reviews the pharmacologically active effects and mechanisms of action of gossypin in recent years, and provides a theoretical basis for it to become a new therapeutic drug.…”