Perinatal Exposure to a Glyphosate Pesticide Formulation Induces Liver Damage in Immature Rat Pups

Abstract

The present study investigated the effects of perinatal exposure to glyphosate-based herbicide (GBH) on liver of immature Wistar rats. Female rats were exposed to GBH (70 mg glyphosate/Kg body weight/day) in drinking water from gestation day 5 and continually up to lactation 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 to GBH-induced Ca2+ influx in liver. In addition, changes in the enzymatic antioxidant defense system, decreased GSH content, lipid peroxidation and protein carbonylation suggest a connection between GBH 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 exposed to GBH. We also detected increased phospho-p65NFκB immunocontent, corresponding to the active form of this transcription factor. Therefore, we propose that excessive amounts of iron induced by perinatal exposure to GBH in offspring’s liver, blood and bone marrow may account for iron-driven hepatotoxicity, which was associated with Ca2+ influx, oxidative damage and inflammation in immature rats. Further studies will clarify whether these events can ultimately impact on liver function.