Picroside II attenuates ischemia/reperfusion testicular injury by alleviating oxidative stress and apoptosis through reducing nitric oxide synthesis

Abstract

Purpose:To investigate the effect of Picroside II on testicular ischemia and reperfusion (l/R) injury and the underlying mechanism.Methods:Sprague-Dawley rats were randomly divided into 4 groups: sham operated group (Sham), Sham with Picroside II treatment group (Sham+ Pic II), l/R group (l/R) and l/R with Picroside II treatment group (I/R+ Pic II). l/R model was established by rotating the left testis 720° in a clock-wise direction for 4 hours. The histopathologic and spermatogenetic evaluation was performed. The apoptosis changes and the levels of HO-1 (heme oxygenase-1), MPO (myeloperoxidase), NOX (NADPH oxidase), SOD (superoxide dismutase), XO (xanthine oxidase) and NOS (nitric oxide synthase) were measured.Results:The seminiferous tubules were damaged in l/R rats, but Picroside II alleviated the changes induced by l/R. The increased level of apoptosis was decreased by Picroside II (P=0.01, 9.05±0.35 vs. 4.85±0.25). The activities of HO-1, MPO, NOX, XO and MDA content were increased and the SOD activity was decreased in l/R (P<0.05) and could be reversed by Picroside II (P=0.03, 405.5±7.5 vs. 304±17U/mgprot; P=0.02, 0.99±0.05 vs. 0.52±0.04 mgprot; P=0.01, 260+7 vs. 189±2 mgprot; P=0.04, 10.95+0.55 vs. 8.75+0.35 U/mgprot; P=0.045, 6.8+0.7 vs. 3.75+0.35 mgprot; P=0.04, 44.5+3.5 vs. 57.5+3.5 mgprot). Western blot showed that the expression of iNOS, nNOS and eNOS were increased in l/R (P<0.05); however, they were decreased after Picroside II treatment (P<0.05).Conclusion:Picroside II attenuated testicular I/R injury in rats mainly through suppressing apoptosis and oxidative stress through reduction of nitric oxide synthesis.

Natural Antioxidants Improve the Vulnerability of Cardiomyocytes and Vascular Endothelial Cells under Stress Conditions: A Focus on Mitochondrial Quality Control

“…Picroside is an active component in Picrorhiza sp. that has strong anti-inflammatory and antioxidant effects [ 95 , 96 ]. Picroside significantly inhibits ROS production in mitochondria, inhibits mPTP opening, increases the MMP, inhibits cytC release from the mitochondria downregulates caspase-3, and suppresses cardiomyocyte apoptosis induced by H/R in cardiomyocytes, suggesting that picroside improves cardiomyocyte activity by reducing ROS production [ 97 ].…”

Luteolin abates reproductive toxicity mediated by the oxido-inflammatory response in Doxorubicin-treated rats

“…O 2 − radicals. 75 –77 The decrease in LPO, RONS levels, and XO activity coupled with increases in antioxidant status following LUT co-treatment may be ascribed to the antioxidative and peroxidation properties of LUT as previously documented, 25,78,79 thereby suppressing oxidative injury in the testis and epididymis of treated rats.…”

Sinapic acid reduces ischemia/reperfusion injury due to testicular torsion/detorsion in rats

“…(Lysiak, 2004; Shimizu et al., 2016). During reperfusion, ROS stimulates the formation and recruitment of inflammatory cytokines (such as IL‐1β and TNF‐α), causing testicular atrophy, germ cell apoptosis, and destruction of spermatogenesis (Altavilla et al., 2012; Li et al., 2019; Turner et al., 2004). In our study, after testicular I/R injury, the TNF‐α, IL‐1β, and IL6 levels of the IR group rats increased significantly compared to those of the sham group rats.…”

“…Apoptosis is an essential physiological process that occurs during normal spermatogenesis; however, the generation of excessive ROS or antioxidant depletion reduces anti‐apoptotic Bcl‐2, leading to the activation of caspases that triggers the apoptotic pathway (Elmore, 2007; Musaogullari et al., 2020; Shaha et al., 2010). Many studies have shown that testicular I/R injury can lead to the generation of excessive ROS and inflammatory factors and increase the apoptosis of spermatogenic cells, leading to infertility (Gultekin et al., 2018; Kostakis et al., 2017; Li et al., 2019). Apoptosis is the cell's natural mechanism for programmed cell death.…”