Home Topics in Depth Science And Environment Multiomics reveal non-alcoholic fatty liver disease in rats following chronic ex

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    Multiomics reveal non-alcoholic fatty liver disease in rats following chronic ex

    Glyphosate-based herbicides (GBH), such as Roundup, are the major pesticides used worldwide1. Residues of GBH are routinely detected in foodstuffs2,3 and drinking water4. Epidemiological data on the human body burden of GBH residues is very limited but evidence suggests that glyphosate and its metabolites are widespread5. The active principle of GBH, glyphosate, is a competitive inhibitor of phosphoenolpyruvate6. Glyphosate acts as a herbicide by inhibiting 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) of the shikimate aromatic amino acid biosynthesis pathway present in plants and some bacteria7.

    Nevertheless, it should be noted that most results from these GBH toxicity studies were obtained at doses far greater than general human population exposure. Doses tested were typically over the glyphosate acceptable daily intake (ADI), which is currently set at 0.3 mg/kg bw/day within the European Union (1.75 mg/kg bw/day in the USA) based on hepatorenal toxicity measurements after chronic exposure in rats16,17. However, no long-term studies investigating the toxicity of complete GBH commercial formulations, which contain a broad spectrum of largely undisclosed “adjuvants” as well as glyphosate, have been conducted (see ref. 9). In an effort to address this gap in commercial GBH toxicity evaluation, a 2-year study was conducted where rats were administered with a Roundup GBH via drinking water at a concentration of 0.1 ppb (0.05 μg/L glyphosate; daily intake 4 ng/kg bw/day), which is an admissible concentration within the European Union (0.1 μg/L) and USA (700 μg/L)18. The results showed that Roundup caused an increased incidence in signs of anatomical pathologies, as well as changes in urine and blood biochemical parameters suggestive of liver and kidney functional insufficiency18.

     

    Conclusions
    The results of the study presented here imply that chronic consumption of extremely low levels of a GBH formulation (Roundup), at admissible glyphosate-equivalent concentrations, are associated with marked alterations of the liver proteome and metabolome. These changes in molecular profile overlap substantially with biomarkers of NAFLD and its progression to NASH. These alterations correlate with the observed signs of hepatic anatomorphological and biochemical pathological changes in this organ18, and as suggested by transcriptome profiling29. Confirmatory studies incorporating testing principles from endocrinology should be performed to investigate potential implications of GBH low dose exposure in the development of metabolic syndrome.

    http://www.nature.com/articles/srep39328

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