Resveratrol Ameliorates Microcystin-LR-Induced Testis Germ Cell Apoptosis in Rats via SIRT1 Signaling Pathway Activation.

Haohao Liu,Phelisters Marwa,Donggang Zhuang,Chuanrui Liu,Jinxia Wu,Yueqin Wang,Rui Wang,Xingde Du,Le Yuan,Shenshen Zhang,Xuemin Cheng,Huizhen Zhang

doi:10.3390/toxins10060235

Abstract

Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by cyanobacteria, is a strong reproductive toxin. Studies performed in rat Sertoli cells and Chinese hamster ovary cells have demonstrated typical apoptosis after MC-LR exposure. However, little is known on how to protect against the reproductive toxicity induced by MC-LR. The present study aimed to explore the possible molecular mechanism underlying the anti-apoptosis and protective effects of resveratrol (RES) on the co-culture of Sertoli–germ cells and rat testes. The results demonstrated that MC-LR treatment inhibited the proliferation of Sertoli–germ cells and induced apoptosis. Furthermore, sirtuin 1 (SIRT1) and Bcl-2 were inhibited, while p53 and Ku70 acetylation, Bax expression, and cleaved caspase-3 were upregulated by MC-LR. However, RES pretreatment ameliorated MC-LR-induced apoptosis and SIRT1 inhibition, and downregulated the MC-LR-induced increase in p53 and Ku70 acetylation, Bax expression, and caspase-3 activation. In addition, RES reversed the MC-LR-mediated reduction in Ku70 binding to Bax. The present study indicated that the administration of RES could ameliorate MC-LR-induced Sertoli–germ cell apoptosis and protect against reproductive toxicity in rats by stimulating the SIRT1/p53 pathway, suppressing p53 and Ku70 acetylation and enhancing the binding of Ku70 to Bax.

Highlights

Cyanobacterial blooms caused by water eutrophication represent a health hazard to humans and animals, evoking global concerns [1,2]
Taken levels, which was similar to the untreated group (Figure 4B). These results indicate that together, these results indicate that RES could protect against Microcystin-leucine arginine (MC-LR)-induced germ cell apoptosis
We used a higher dose than that suggested by the World Health Organization (WHO) (1 μg/L), the concentration is usually much higher in natural water (10 μg/L)

Summary

Introduction

Cyanobacterial blooms caused by water eutrophication represent a health hazard to humans and animals, evoking global concerns [1,2]. Microcystins (MCs) are a family of over 100 different structural analogue compounds with seven stable cyclic heptapeptide structures, and are produced by cyanobacteria such as Microcystis [3]. Microcystin-leucine arginine (MC-LR) is the most abundant and most toxic MC found in natural water, causing growing environmental and public health issues [4]. Humans are most likely exposed to MC-LR through the consumption of contaminated water and food resources, and dermal exposure/inhalation during recreational activities in contaminated surface. A safety limit (1.0 μg/L) of MC-LR has been set by World Health Organization (WHO). The concentration is usually much higher in natural water.

Methods

Results

Conclusion