Melatonin Ameliorates Diquat-Induced Testicular Toxicity via Reducing Oxidative Stress, Inhibiting Apoptosis, and Maintaining the Integrity of Blood-Testis Barrier in Mice

Abstract

Diquat is a fast, potent, and widely used bipyridine herbicide in agriculture and it induces oxidative stress in several animal models. However, its genotoxic effects on the male reproductive system remain unclear. Melatonin is an effective free-radical scavenger, which has antioxidant and anti-apoptotic properties and can protect the testes against oxidative damage. This study aimed to investigate the therapeutic effects of melatonin on diquat-induced testicular injury in mice. The results showed melatonin treatment alleviated diquat-induced testicular injury, including inhibited spermatogenesis, increased sperm malformations, declined testosterone level and decreased fertility. Specifically, melatonin therapy countered diquat-induced oxidative stress by increasing production of the antioxidant enzymes GPX1 and SOD1. Melatonin treatment also attenuated diquat-induced spermatogonia apoptosis in vivo and in vitro by modulating the expression of apoptosis-related proteins, including P53, Cleaved-Caspase3, and Bax/Bcl2. Moreover, melatonin restored the blood-testicular barrier by promoting the expression of Sertoli cell junction proteins and maintaining the ordered distribution of ZO-1. These findings indicate that melatonin protects the testes against diquat-induced damage by reducing oxidative stress, inhibiting apoptosis, and maintaining the integrity of the blood–testis barrier in mice. This study provides a theoretical basis for further research to protect male reproductive health from agricultural pesticides.

Naringenin ameliorates cytotoxic effects of bisphenol A on mouse Sertoli cells by suppressing oxidative stress and modulating mitophagy: An experimental study

“…Feng et al showed that naringin reduced cerebral ischemia-reperfusion damage in rats through mitophagy activation. In their study, naringin could suppress apoptosis and inhibit the translocation of Parkin to the mitochondria in the ischemia-reperfused rat brains (12). Conversely, excessive mitophagy induces apoptosis in cancerous cells, in particular (39).…”

“…BPA induces Sertoli cell death in rodents by causing mitochondrial dysfunction and excessive ROS generation (4). Feng et al showed that BPA induces cell cycle arrest and apoptosis by preventing ROS levels in the porcine Sertoli cells (12). It is, therefore, necessary to find preventive and therapeutic agents to address BPA-induced reproductive toxicity.…”

Erythrocyte membrane biomimetic EGCG nanoparticles attenuate renal injury induced by diquat through the NF-κB/NLRP3 inflammasome pathway

“…In cases of large ingestions, patients can develop symptoms of acute renal failure ( Tanen et al, 1999 ; Fortenberry et al, 2016 ; Huang et al, 2021 ). Additionally, DQ can exert toxic effects on other organ systems, including the liver ( Burk Rf Fau - Lawrence et al, 1980 ), lungs ( Manabe J Fau - Ogata et al, 1986 ), heart, central nervous system ( Lu et al, 2022 ), digestive tract, airways ( Tanen et al, 1999 ), skin, and reproductive system ( Guangcai et al, 2022 ; Zhou and Lu, 2022 ; Yang et al, 2023 ).…”