A Mixture of Endocrine Disruptors and the Pesticide Roundup® Induce Oxidative Stress in Rabbit Liver When Administered under the Long-Term Low-Dose Regimen: Reinforcing the Notion of Real-Life Risk Simulation

Abstract

Humans are exposed to xenobiotic mixtures daily through the long-term, low-dose regimen. Investigations designed to simulate this exposure profile approach the real-life risk simulation (RLRS) idea of modern toxicology. The purpose of the present study was to investigate the effects of 12-month exposure of New Zealand rabbits to a xenobiotic mixture comprising seven endocrine disruptors (EDs), which are chemical substances raising great concerns for human health, as well as the herbicide glyphosate, and its commercial formulation Roundup®, on blood and tissues redox status. It is reported herein that at the systemic level, the administration of the EDs mixture induced perturbations of blood redox homeostasis at 3 months, whereas at 6 and 12 months, it activated redox adaptations. Contrariwise, exposure to glyphosate and Roundup®, individually, caused mainly disturbances of blood redox equilibrium. At the tissue level, particularly in the liver, the administration of both the EDs mixture and Roundup® induced oxidative stress, whereas glyphosate did not affect it. The RLRS notion appears to be confirmed through these findings. Indeed, the administration of the EDs mixture and Roundup®, under the long-term, low-dose regimen, elicited detrimental effects on the redox status of the liver, a crucial tissue with a valuable biological role in the detoxification of organisms from xenobiotics.

Glyphosate and AMPA in Human Urine of HBM4EU-Aligned Studies: Part B Adults

“…Gut health may also have an influence on brain function via the gut-brain axis [ 42 ]. Overall, there is a need for new studies exploring the links between glyphosate and human health effect markers at environmentally relevant concentrations alone or in combination with other pollutants, searching for links with observed effects found in animal and in vitro studies (e.g., Vardakas et al, 2022) [ 43 ].…”

Heavy Metals, Halogenated Hydrocarbons, Phthalates, Glyphosate, Cordycepin, Alcohol, Drugs, and Herbs, Assessed for Liver Injury and Mechanistic Steps

“…Aside from the NHL issue but due to its systemic detection in the human body, glyphosate may theoretically enter various organs including the liver. In consideration of these aspects, a variety of reports fo-cused on a possible hepatotoxic potential of glyphosate in both, humans [268] and animals [269,270]. High LTs have been observed in a farmer from India with acute liver failure following glyphosate poisoning, who acutely ingested 25 mL glyphosate and had a history of chronic low dosed exposure to glyphosate and alcohol use: serum activities of ALT were 1311 U/L and AST 1021 U/L [271].…”

“…Mechanistic views of steps leading to liver injury by glyphosate are primarily based on animal studies [263,269,280]. Consensus exists that glyphosate produces ROS in the hepatocytes, which in turn cause injurious changes of cell protein and structural membrane proteins via unsaturated lipid peroxidation under regulation of antioxidants, GSH, and catalase [269,280].…”

“…Mechanistic views of steps leading to liver injury by glyphosate are primarily based on animal studies [263,269,280]. Consensus exists that glyphosate produces ROS in the hepatocytes, which in turn cause injurious changes of cell protein and structural membrane proteins via unsaturated lipid peroxidation under regulation of antioxidants, GSH, and catalase [269,280]. Glyphosate is a competitive inhibitor of the shikimate pathway that allows aromatic amino acid biosynthesis in plants, features explaining the herbicide property of glyphosate [263].…”

Evaluation of the antioxidant potency of Greek honey from the Taygetos and Pindos mountains using a combination of cellular and molecular methods

“…Investigations using laboratory animals designed to evaluate the toxicological profile of pesticide mixtures, administered at concentrations below the existing regulatory limits, have revealed the manifestation of detrimental effects when assessed by metabolomics contrary to the conventional biochemical measurements ( 89 ). Furthermore, previous studies have reported that exposure to low levels of pesticides under the long-term, low-dose regimen perturbs the redox homeostasis and induces oxidative stress, thus causing adverse effects on the organism level in the long term ( 90 , 91 ). In the present study, organic raw honey samples were used, which are free of pesticides ( 92 ).…”