Perinatal exposure to a glyphosate pesticide formulation induces offspring liver damage

• Published in: Toxicology and applied pharmacology 2022-11, Vol.454, p.116245, Article 116245
• Main Authors: Rieg, Carla Elise Heinz, Cattani, Daiane, Naspolini, Nathalia Ferrazzo, Cenci, Vitoria Hayduck, de Liz Oliveira Cavalli, Vera Lúcia, Jacques, Amanda Virtuoso, Nascimento, Marcus Vinicius Pereira Dos Santos, Dalmarco, Eduardo Monguilhott, De Moraes, Ana Carolina Rabello, Santos-Silva, Maria Cláudia, Silva, Fátima Regina Mena Barreto, Parisotto, Eduardo Benedetti, Zamoner, Ariane
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Calcium; Drinking Water; Female; Glycine - analogs & derivatives; Glyphosate; Hepatotoxicity; Herbicides - toxicity; Interleukin-6; Iron; Iron overload; Liver; Liver Diseases; Oxidative stress; Pesticides; Pregnancy; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Transaminases; Transferrins; Tumor Necrosis Factor-alpha; Type C Phospholipases
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2022.116245

The present study investigated the effects of perinatal exposure to glyphosate-based herbicide (GBH) in offspring's liver. Pregnant Wistar rats were exposed to GBH (70 mg glyphosate/Kg body weight/day) in drinking water from gestation day 5 to postnatal day 15. The perinatal exposure to GBH increased 45Ca2+ influx in offspring's liver. Pharmacological tools indicated a role played by oxidative stress, phospholipase C (PLC) and Akt pathways, as well as voltage-dependent Ca2+ channel modulation on GBH-induced Ca2+ influx in offspring's liver. In addition, changes in the enzymatic antioxidant defense system, decreased GSH content, lipid peroxidation and protein carbonylation suggest a connection between GBH-induced hepatotoxic mechanism and redox imbalance. The perinatal exposure to GBH also increased the enzymatic activities of transaminases and gamma-glutamyl transferase in offspring's liver and blood, suggesting a pesticide-induced liver injury. Moreover, we detected increased iron levels in liver, blood and bone marrow of GBH-exposed rats, which were accompanied by increased transferrin saturation and decreased transferrin levels in blood. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were increased in the liver of rats perinatally exposed to GBH, which were associated with. Increased phospho-p65NFκB immunocontent. Therefore, we propose that excessive amounts of iron in offspring's liver, blood and bone marrow induced by perinatal exposure to GBH may account for iron-driven hepatotoxicity, which was associated with Ca2+ influx, oxidative damage and inflammation. Further studies will clarify whether these events can ultimately impact on liver function. [Display omitted] •Glyphosate-based herbicide leads to iron overload.•Perinatal exposure to glyphosate leads to oxidative damage in liver.•Glyphosate-induced hepatotoxicity is associated with calcium influx.•Glyphosate causes GSH depletion and lipid peroxidation.