Abstract
The potential toxicity of glyphosate, a widely used broad-spectrum herbicide, is currently a great matter of debate. As vertebrate insectivores, lizards protect plants from herbivorous insects increasing plant biomass via the trophic cascade and represent an important link between invertebrates and higher predators. A negative effect of glyphosate on lizards' survival could have major impacts at the ecological levels. In this study, we investigated the effects of the exposure to low doses of glyphosate on the liver of the wall lizard Podarcis siculus, a suitable bioindicator of soil pollution. Two different doses of pure glyphosate (0.05 and 0.5 μg/kg body weight) were orally administered every other day for 3 weeks to sexually mature males and females. The results demonstrated that both doses, despite being very low, are toxic for the liver that showed clear signs of suffering, regardless of sex. The histological analysis provided a scenario of severe hepatic condition, which degenerated until the appearance of fibrotic formations. The morphological observations were consistent with a loss of liver physiological functions. Immunocytochemical investigations allowed us to detect an involvement of antioxidant/cytoprotective proteins, such as superoxide dismutase 1 (Cu/Zn SOD, known as SOD1), glutathione peroxidase 1 (GPx1), metallothionein (MT), and tumor suppressor protein 53, (p53) suggesting that the liver was trying to react against stress signals and damage induced by glyphosate. Finally, in situ hybridization and Real-Time PCR analysis showed the upregulation of estrogen receptor α and vitellogenin gene expression, thus demonstrating the xenoestrogenic action of glyphosate. The imbalance of the hormonal homeostasis could threaten the lizards' reproductive fitness and survival, altering the trophic cascade.
Highlights
During the last two decades, environmental pollution caused by the intense use of herbicides is becoming an outstanding problem that can affect human and animal health through feeding [1, 2]
Gly herbicidal action derives from the inhibition of the enolpyruvylshikimate-3-phosphate synthase (EPSPS), a key plant enzyme involved in the synthesis of aromatic amino acids essential for plants growth and for the activation of defence mechanisms in vegetal cells [5]
Classified by the United States Environmental Protection Agency (EPA) as “nontoxic and not an irritant” and by the European Food Safety Authority (EFSA) as “not carcinogenic to humans,” multiple lines of evidence suggest that Glyphosate-based herbicides (GBHs) pose a serious health risk to wildlife [6,7,8,9,10,11,12,13,14,15]
Summary
During the last two decades, environmental pollution caused by the intense use of herbicides is becoming an outstanding problem that can affect human and animal health through feeding [1, 2]. Gly herbicidal action derives from the inhibition of the enolpyruvylshikimate-3-phosphate synthase (EPSPS), a key plant enzyme involved in the synthesis of aromatic amino acids essential for plants growth and for the activation of defence mechanisms in vegetal cells [5]. Since this enzyme is absent in animals, it has long been assumed that glyphosate would not affect non-target species and, today, this is a great matter of debate. Many studies reported controversial results on Gly effects, especially in humans [18]; in addition, most of them focused on the toxicity of the commercial formulations of Gly, such as the Roundup (Monsanto), but the adjuvants or surfactants can often enhance the Gly toxic effects [19]
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