de Liz Oliveira Cavalli VL, Cattani D, Elise Heinz Rieg C, Pierozan P, Zanatta L, Benedetti Parisotto E, Wilhelm Filho D, Regina Mena Barreto Silva F, Pessoa-Pureur R, Zamoner A.
Free Radic Biol Med. 2013 Jun 29. pii: S0891-5849(13)00326-2. doi: 10.1016/j.freeradbiomed.2013.06.043. [Epub ahead of print]
Source
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis-Santa Catarina, Brazil.
Open access: http://www.ncbi.nlm.nih.gov/pubmed/23820267

Abstract
Glyphosate is the primary active constituent of the commercial pesticide Roundup®. The present results show that acute Roundup® exposure at low doses (36ppm, 0.036g/L) for 30min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca2+ concentration by opening L-type voltage-dependent Ca2+ channels (L-VDCC) as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca2+ overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30min incubation of testis with glyphosate alone (36ppm) also increased 45Ca2+ uptake. These events have been prevented by the antioxidants Trolox® and ascorbic acid. Activated protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K) and the mitogen-activated protein kinases (MAPKs), such as ERK1/2 and p38MAPK have played a role in eliciting Ca2+ influx and cell death. Roundup® decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric reactive species (TBARS) and protein carbonyls. Also, exposure to the glyphosate-Roundup® has stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione-S-transferase, gamma-glutamyl transferase (γGT), catalase, superoxide dismutase and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We could propose that Roundup® toxicity, implicating in Ca2+ overload, cell signaling misregulation, stress response of the endoplasmic reticulum and/or depleted antioxidant defenses could contribute to Sertoli cell disruption of spermatogenesis that could impact male fertility.