Abstract
Glyphosate (N-phosphonomethyl-glycine, GLP) is the most popular herbicide used worldwide. This study aimed to investigate the effects of glyphosate on rats' liver function and induction of pathological changes in ion levels and oxidative stress in hepatic tissue. Sprague-Dawley rats were treated orally with 0, 5, 50, and 500 mg/kg body weight of the GLP. After 5 weeks of treatment, blood and liver samples were analyzed for biochemical and histomorphological parameters. The various mineral elements content in the organs of the rats were also measured. Significant decreases were shown in the weights of body, liver, kidney and spleen between the control and treatment groups. Changes also happened in the histomorphology of the liver and kidney tissue of GLP-treated rats. The GLP resulted in an elevated level of glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and IL-1β in the serum. Besides, decreased total superoxide dismutase (T-SOD) activity and increased malondialdehyde (MDA) contents in the serum, liver, and kidney indicated the presence of oxidative stress. Moreover, increase of hydrogen peroxide (H2O2) level and catalase (CAT) activity in the serum and liver and decrease of glutathione (GSH) and lutathione peroxidase (GSH-Px) activity in the kidney tissue further confirmed the occurrence of oxidative stress. The results of RT-PCR showed that the mRNA expressions of IL-1α, IL-1β, IL-6, MAPK3, NF-κB, SIRT1, TNF-α, Keap1, GPX2, and Caspase-3 were significantly increased in the GLP-treated groups compared to the control group. Furthermore, PPARα, DGAT, SREBP1c, and SCD1 mRNA expressions were also remarkably increased in the GLP-treated groups compared to the control group. In addition, aluminum (Al), iron (Fe), copper (Cu), zinc (Zn), and magnesium (Mg) levels were showed a significant difference reduction or increase in rat liver, kidney, spleen, lung, heart, muscle, brain, and fat tissues. These results suggested that glyphosate caused obvious damage to rats' liver and caused various mineral elements content imbalances in various organs of rats. Ion imbalance could weaken antioxidant capacity and involve in the mechanism of liver oxidative damage caused by GLP.
Highlights
Glyphosate (GLP) is a non-selective, post-emergence herbicide used for weed control in various crops, especially in rice, maize and soybean (Coutinho et al, 2005)
After administration of GLP, there was a significant distinction in rat body weight between the control group and the 500 mg/kg GLP group (p < 0.05, Table 2)
Hepatic IL-1α and IL1β mRNA expression were significantly increased after GLP exposure compared with the control group (p < 0.05); IL-6, MAPK3, SIRT1, TNF-α, GPX2, and Caspase-3 mRNA expression were significantly increased in the 50 mg/kg and 500 mg/kg GLP-treated group compared with the control group (p < 0.05); NF-κB mRNA expression showed a significant increase in the 50 mg/kg GLP-treated group compared with the control group (p < 0.05); at the same time, we observed a significant increase in Keap1 mRNA expression in 5 mg/kg GLP-treated group compared with the control group (p < 0.05)
Summary
Glyphosate (GLP) is a non-selective, post-emergence herbicide used for weed control in various crops, especially in rice, maize and soybean (Coutinho et al, 2005). Eighty percent of genetically modified crops were GLP-resistant plants, such as corn, soy, cotton and canola and so on (Williams et al, 2000). American farmers have widely used anti-GLP crops since 1996 (Frisvold et al, 2010). It means there will be much more glyphosate in soil and water environment. Study has reported that GLP and its metabolite such as aminomethylphosphonic acid (AMPA) and formaldehyde were found in the soil and rivers (Temple and Smith, 1992). It has been extensively demonstrated that exposure to GLP leads to oxidative stress in several tissue, including the livers and kidneys (Beuret et al, 2005; El-Shenawy, 2009; Modesto and Martinez, 2010; Larsen et al, 2012; Cattani et al, 2014)
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