Beneficial Effects of Quercetin on Microcystin-LR Induced Tight Junction Defects.

Yuan Zhou,Miaomiao Zhang,Zongxiang Tang,Mei Xue,Xuyang Wang,Changming Wang,Yunfei Jiang,Guang Yu

doi:10.3389/fphar.2021.733993

Abstract

Quercetin has numerous functions including antioxidant and anti-inflammatory effects. The beneficial effect of quercetin against microcystin-LR (MC-LR)-induced testicular tight junctions (TJs) defects in vitro and in vivo were investigated. Significant reductions in transepithelial electrical resistance, occludin, and zonula occludens-1(ZO-1) levels were detected in the MC-LR-treated TM4 cells, and quercetin attenuated these effects. Interestingly, quercetin suppressed MC-LR-induced phosphorylation of protein kinase B (AKT). It effectively inhibited the accumulation of reactive oxygen species (ROS) in cells stimulated by MC-LR. In addition, ROS inhibitors blocked the TJ damage that is dependent on the AKT signaling pathway induced by MC-LR. In conclusion, our results suggest that alleviates MC-LR-impaired TJs by suppressing the ROS-regulated activation of the AKT pathway.

Highlights

Microcystins (MCs), a cyclic heptapeptide, regard as major hazards to mammals (Hu et al, 2016)
MC-LR can destroy the integrity of the blood-testis barrier (BTB) by regulating tight junctions (TJs) (Zhou et al, 2020)
It is well known that zonula occludens-1 (ZO-1), claudin, and occludin are the main protein of TJs (Qiu et al, 2016), and their changes could arrest spermatogenesis, leading to the decline of sperm concentration

Summary

Introduction

Microcystins (MCs), a cyclic heptapeptide, regard as major hazards to mammals (Hu et al, 2016). It has detected more than 100 MCs variants, of which microcystin-LR (MC-LR) is the most widely studied (Zhou et al, 2014). Accumulating evidence has shown that MC-LR has various toxic effects containing hepatotoxicity and neurotoxicity (Hinojosa et al, 2019; Wang et al, 2019). The blood-testis barrier (BTB) is mainly composed of tight junctions (TJs), adherent junctions, and gap junctions (Squadrito et al, 2016). TJs which are observed between Sertoli cells play a pivot role in BTB integrity (Zhou et al, 2018). MC-LR induces TJ dysfunction, resulting in sperm abnormality (Zhang et al, 2013; Chen et al, 2018; Zhang et al, 2018)

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Results

Conclusion