| Glyphosate is the active component of several commercial formulations,as in Roundup(?),which use as a broad-spectrum herbicide on field crops,particularly small grains,which are then used in livestock,poultry,and human.The commercial form contains other adjuvants with glyphosate,thereby increasing their impact.As with most agricultural chemicals,the possibility exists for accidental contamination of feedstuffs to be used in poultry and livestock feeds after harvesting.Previously,people considered glyphosate and glyphosate-based herbicides to be safe for creatures and the environment.Nevertheless,increasing studies have shown that the incidence of multiple diseases like cytotoxicity,neurotoxicity and reproductive toxicity in pure glyphosate and commercial formulations.Also,it has been extensively shown that oxidative stress was induced in tissues,which has been exposed to glyphosate.Some studies in vitro demonstrated that the adjuvants in Roundup(?) were more toxic compared with glyphosate alone.Some studies reported that impaired sulfate transport and inhibition of the activity of enzymes for the CYP450 family in the various members by glyphosate.An in vitro study indicated glyphosate was more susceptible to the pathogenic bacteria.In addition,glyphosate was able.to disrupt the gut bacteria’s homeostasis.So,there is a danger of having negative effects on the health of animals and humans.The purpose of this study was to explore the effects of glyphosate on the expression of CYP family in the liver and small intestines,hepatic lipid metabolism,tight junction in the small intestines,including embryos(15ED),hatching day,and 7-day-old.1-Effect of in ovo glyphosate injection on embryonic development,serum biochemistry,and antioxidant status in hatching chicksThis experiment was designed to determine the toxicity of glyphosate or Roundup(?) on hatchability,serum biochemistry,antioxidant enzyme activity.Four hundred and fifty fertilized eggs were obtained from Huafeng breeder hens(Jiangsu,China).On ED six,eggs were randomly divided into three groups:CON(control group,n=150),GLP(10 mg glyphosate/Kg egg mass,n=150),and RU(10mg of the active ingredient glyphosate/Kg egg mass,n=1 50).Hatching day,the results showed that a decrease in the hatchability rate in chicks treated with Roundup(?)(66%)compared to other groups.Furthermore,the results showed that serum protein profiles were linearly significantly increased of serum phosphor,uric acid,aspirate aminotransferase,alanine transaminase,and alkaline phosphatase in groups treated with Roundup(?),as well as oxidative stress was observed in the treated chicks,the glyphosate and Roundup(?) decrease of total superoxide dismutase and catalase activity in the serum.Moreover,on day 7,significant change(P<0.05)was observed in body weights in chicks that were treated with Roundup(?) compared to other groups.Furthermore,a significant decrease(P<0.05)of serum albumin and total superoxide dismutase activity was observed in Roundup(?) compared to other groups,also a sign1ficant increase(P<0.05)of serum uric acid in chicks treated with glyphosate or Roundup(?) compare to the control.Furthermore,a significant increase(P<0.05)of serum y-glutamyl transpeptidase was observed in Roundup(?) compared to other groups.These results show that Roundup(?) as a probable decrease of hatchability than the active ingredient itself(glyphosate),with decreasing body weight on day 7.Exposure to glyphosate alone or Roundup(?) caused serum parameters imbalances and oxidative stress,also induced a variety of liver biochemical alterations that might impair normal organ functioning in hatched chicks.2-Disruption of cytochrome P450 enzymes in the liver of chicks exposed to glyphosateThe aim of the present study was to explore the effects of glyphosate or Roundup(?) on the changes in the gene expression of CYP family members,ABC family transporters,and modulation of the proinflammatory cytokines in the liver tissue.On ED six,eggs were randomly divided into three groups:CON(control group,n=150),GLP(10 mg glyphosate/Kg egg mass,n=150),and RU(10mg of the active ingredient glyphosate/Kg egg mass,n=150).The results showed that the levels of alanine transaminase were significantly raised(P<0.05)in Roundup(?) treated group at different time points(ED 15,hatching day,and day 7).Aspirate aminotransferase enzymes w as significantly increased(P<0.05)after hatching in groups treated glyphosate or Roundup(?) compared with the control.Regard to the activities of antioxidant enzymes of the liver,at ED 15,total superoxide dismutase and malondialdehyde content were significantly raised(P<0.05)in the Roundup(?)lreated group.In addition,the activity of catalase activity was significantly decreased(P<0.05)in Roundup(?) and glyphosate groups compared with the control.Furthermore,malondialdehyde content was significantly raised(P<0.05)in the glyphosate and Roundup(?) treated groups at hatching day compared to the control group.On day 7,the activity of catalase activity was significantly decreased(P<0.05)in glyphosate and Roundup(?) groups compared with the control.Moreover,the level of malondialdehyde of the liver in glyphosate and Roundup(?)groups was significantly raised(P<0.05)compared to the control group.Moreover,histopathological changes were spotted in the liver tissues.At ED 15,hepatic CYP1A2,CYP1A4,CYP1B1,and MDR1 mRNA expressions were significantly decreased(P<0.05)after Roundup(?) exposure compared with the control group,but CYP3A5 mRNA expression was significantly increased(p<0.05)in the treated group with glyphosate or Roundup(?)compared with the control group.With respect to hatching day,hepatic CYP1A2 and CYP1A4 expressions were significantly increased(P<0.05)after glyphosate exposure,suppression of CYP1C1 mRNA expression was significant(P<0.05)after Roundup(?)exposure compared with the control group.The proinflammatory cytokines genes IFNY and IL-1B expression were significantly increased(P<0.05)after Roundup(?) exposure compared with the control group.At post hatch day 7,hepatic CYP3A5 was significantly suppressed(P<0.05)in chicks treated with glyphosate or Roundup(?).Also,hepatic CYP1B1 and MRP2 were significantly suppressed(P<0.05)by chickens treated with Roundup(?),but CYP1C1 and IFNY mRNA expression were significantly increased(p<0.05)in the treated group with Roundup(?)compared with the control group.Exposure of glyphosate caused to increase liver function enzymes,histopathological alterations,and induced oxidative stress in chicks.Moreover,the toxicity of pure glyphosate and Roundup(?)has the ability to modulate the expression of cytochrome P450,MDR1 and MRP2 transporters in the liver,and thus may cause dysfunction of the hepatic enzymes system in chicks.3-Effects of glyphosate exposure on hepatic lipid metabolism in chicksThe aim of the present study was to investigate the toxic effects of exposure to pure glyphosate or Roundup(?) on lipid metabolism in chicks.On ED six,eggs were randomly divided into three groups:CON(control group,n=150),GLP(10 mg glyphosate/Kg egg mass,n=150),and RU(10mg of the active ingredient glyphosate/Kg egg mass,n=150).The results showed that,at hatching day,serum concentrations of triglyceride were significantly increased(P<0.05)with glyphosate.At day 7,serum concentrations of highdensity lipoprotein cholesterol were significantly increased(P<0.05)with control compared to the other groups.Moreover,triglycerides and cholesterol levels in the glyphosate and Roundup(?) groups significantly increased in hatching day(P<0.05).Furthermore,the lowdensity lipoprotein cholesterol levels on day 7 showed an increase in both the glyphosate and Roundup(?) groups(p<0.05)compared to the control.Liver histological observation in both the glyphosate and Roundup(?) groups showed excessive lipid deposits.The relative expression levels of the genes SCD and HMGCS1 in the glyphosate and Roundup(?) groups showed a significant increase(p<0.05)in ED 15.In addition,the relative expression levels of the genes ACACA,FASN,SCD,SREBF1,and SREBF2 in the glyphosate and Roundup(?)groups showed a significant increase in hatching day(p<0.05).Furthermore,the relative expression levels of the genes PPARA and SREBF1 in the glyphosate and Roundup(?) groups showed a significant increase in day 7(p<0.05)compared to the control.The current study demonstrated that glyphosate can probably cause disruption of lipid metabolism during embryo genesis and after hatching,accompanied by an increase of lipid content in both serum and liver tissue.These alterations in hepatic lipid metabolism might result from high lipogenesis in chicks hepatocytes through increasing expression of lipid metabolism related genes.4-Toxic effects of glyphosate exposure on cytochrome P450 enzymes,barrier function,and morphological changes in small intestines of chicksThe present study focused specifically on reviewing the expression of CYP,tight junction,and related inflammatory genes in the small intestine.On ED six,eggs were randomly divided into three groups:CON(control group,n=150),GLP(10 mg glyphosate/Kg egg mass,n=150).and RU(10mg of the active ingredient glyphosate/Kg egg mass,n=150).The results showed that oxidative stress was observed in the chicks treated with glyphosate or Roundup(?).Furthermore,histopathological changes were spotted in the small intestine tissues,such as congestion of blood vessels,increased cellularity of lamina propria,a fusion of villi.complete fusion of some intestinal villi,decreased number of goblet cells,and necrosis of some submucosal epithelial cells in chicks,especially in age after hatching.Modulation of expression genes involved in biotransformation(CYP1A2,CYP1A4,CYP3A5.CYP1B1,CYP1C1,MDR1 and MRP2)for the small intestine was observed in the glyphosate or Roundup(?) groups compared to the control.Disruption of genes(ZO-I,ZO2,Claudin-1,Claudin-3,JAM2 and Occludin),and the proinflammatory cytokines(IFNY,IL-1B and IL-6)for the small intestine was also observed in the glyphosate or Roundup(?)groups compared to the control.The toxicity of pure glyphosate and Roundup(?) can probably cause disruption of the small intestine of chicks before and after hatching by the expression of cytochrome P450,MDR1,MRP2 transporters,and tight junction related genes in the small intestine.In summary,the current study demonstrated that Roundup(?) as a probable decrease of hatchability than the active ingredient itself(glyphosate).Exposure to glyphosate alone or Roundup(?) caused serum parameters imbalances.Furthermore,disruption of lipid metabolism and modulate the expression of cytochrome P450,MDR1 and MRP2 transporters in the liver and small intestines of chicks.Moreover,tight junction related genes was modulated in the small intestine of embryos and chicks,which may increase the potential health risks to the animal. |
