Effects of glyphosate residues and different concentrate feed proportions in dairy cow rations on hepatic gene expression, liver histology and biochemical blood parameters.

Ann-Katrin Heymann,Jana Frahm,Sven Dänicke,Nares Trakooljul,Liane Hüther,Ulrich Meyer,Dirk Von Soosten,Fabian Billenkamp,Susanne Bühler,Karina Schnabel,Jens Peter Teifke,Susanne Kersten,Ibukun Ogunade

doi:10.1371/journal.pone.0246679

Ann-Katrin Heymann, Jana Frahm + Show 11 more

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https://doi.org/10.1371/journal.pone.0246679

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Abstract

Glyphosate (GLY) is worldwide one of the most used active substances in non-selective herbicides. Although livestock might be orally exposed via GLY-contaminated feedstuffs, not much is known about possible hepatotoxic effects of GLY. As hepatic xenobiotic and nutrient metabolism are interlinked, toxic effects of GLY residues might be influenced by hepatic nutrient supply. Therefore, a feeding trial with lactating dairy cows was conducted to investigate effects of GLY-contaminated feedstuffs and different concentrate feed proportions (CFP) in the diets as tool for varying nutrient supply to the liver. For this, 61 German Holstein cows (207 ± 49 days in milk; mean ± standard deviation) were either fed a GLY-contaminated total mixed ration (TMR, GLY groups, mean GLY intake 122.7 μg/kg body weight/day) or control TMR (CON groups, mean GLY intake 1.2 μg/kg body weight/day) for 16 weeks. Additionally, both groups were further split into subgroups fed a lower (LC, 30% on dry matter basis) or higher (HC, 60% on dry matter basis) CFP resulting in groups CONHC (n = 16), CONLC (n = 16), GLYHC (n = 15), GLYLC (n = 14). Blood parameters aspartate aminotransferase, γ-glutamyltransferase, glutamate dehydrogenase, cholesterol, triglyceride, total protein, calcium, phosphorus, acetic acid and urea and histopathological evaluation were not influenced by GLY, whereas all mentioned parameters were at least affected by time, CFP or an interactive manner between time and CFP. Total bilirubin blood concentration was significantly influenced by an interaction between GLY and CFP with temporarily elevated concentrations in GLYHC, whereas the biological relevance remained unclear. Gene expression analysis indicated 167 CFP-responsive genes, while seven genes showed altered expression in GLY groups compared to CON groups. Since expression changes of GLY-responsive genes were low and liver-related blood parameters changed either not at all or only slightly, the tested GLY formulation was considered to have no toxic effects on the liver of dairy cows.

Highlights

Glyphosate (GLY; N-phosphonomethylglycine) is one of the most used active substances in herbicides worldwide [1]
The concentration of urea started to increase from week 4 onwards in Low CFP groups (LC) groups while high CFP groups (HC) groups maintained their urea levels until the end of the experiment giving rise to significant interactions between concentrate feed proportions (CFP) and time
Cholesterol levels remained constant until week 12 in HC groups and dropped slightly thereafter while a linear decrease was noticed in LC groups from week 4 irrespective of GLY exposure, which explained the significant interactions between time and CFP

Summary

Introduction

Glyphosate (GLY; N-phosphonomethylglycine) is one of the most used active substances in herbicides worldwide [1]. Ruminal absorption capacity and systemic absorption of GLY appear to be low [5], GLY residues were detected in different organs such as liver, intestine or muscles of German dairy cows [6]. In this context, the liver is of special interest, since next to its key role in energy metabolism, it is responsible for the degradation and excretion of xenobiotics like herbicides [7, 8]. In order to get further insights, putative hepatotoxicity of GLY at different hepatic nutrient status was addressed in the present investigations

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