The Mechanisms Of Subacute Ruminal Acidosis Induced Oxidative Stress In Ruminants

The liver is the most complex digestive organ in animals,which has an important role in the digestion,absorption,excretion and detoxification.Feeding a high grain diet to goats and cows resulted in the increased entry of lipopolysaccharide(LPS)into the liver via portal circulation and trigger a systemic inflammation and oxidative stress as a result of reduced hepatic clearance of LPS.The objectives of this study were to investigate the mechanism of oxidative stress triggered by induced subacute ruminal acidosis in the liver and rumen epithelium of lactating cows and liver of lactating goats and to evaluate the effect of sodium butyrate against the negative effect of high grain diet induced subacute ruminal acidosis in lactating goats.1-LIPOPOLYSACCHARIDE DERIVED FROM THE DIGESTIVE TRACT PROVOKES OXIDATIVE STRESS IN THE LIVER OF DAIRY COWS FED HIGH-GRAIN DIET.The aims of this study were to investigate oxidative stress parameters and to study the molecular mechanism induced by grain diet-induced subacute ruminal acidosis(SARA)in mid-lactation cows.Twelve holstein-friesian cows with an average weight of 455 ± 28 kg were divided into two groups and subjected to two diets over eighteen weeks:either low-grain(forage to concentrate 6:4)or a high-grain(forage to concentrate4:6)diet based on dry matter.Being fed a long-term high-grain diet resulted in a significant decrease in rumen pH,a significant increase in ruminal lipopolysaccharide(LPS)at 4 hours post feeding in the morning.The increase was also observed in lipopolysaccharide(LPS)concentrations in the hepatic vein,portal vein and jugular vein blood plasma as well as depressed milk yield in a high grain diet.Cows fed a high-grain diet(HG)had lower levels of catalase(CAT)and glutathione peroxidase(GPx)activity and total antioxidant capacity(T-AOC)than cows fed a low-grain diet(LG).However,superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were higher in both the liver and the plasma of high-grain(HG)cows than in low-grain(LG).Positive correlations were seen between plasma LPS versus,plasma MDA,hepatic MDA,and hepatic SOD activity,whereas plasma GPx and hepatic GPx were negatively correlated with plasma LPS.The relative mRNA abundances of CAT and glutathione Peroxidasel(GPX1)were significantly decreased in the liver of cows fed a high-grain diet than that fed alow-grain diet,whereas superoxide dismutasel(SOD1)was significantly increased in cows fed a high-grain diet than cows fed alow-grain diet.The expression levels of nuclear factor E2 related factor2(Nrf2)genes,NAD(P)H,quinone 1(NQO1),metallothionein 1E(MT1E),the UDP glucuronosyltransferase 1 family,polypeptide A1(UGT1A1),microsomal glutathione S-transferase 3(MGST3),and metallothionein-1A(MT1A)were downregulated,whereas nuclear factor kappa B(NF-kB)was upregulated,in cows fed a high-grain diet.Furthermore,Nrf2 total protein and mRNA levels were significantly lower than in low-grains.Our results demonstrate the relationship between the translocated LPS and the suppression of cellular antioxidant defense capacity,which leading to increased oxidative stress and suggest that the Nrf2-dependent antioxidant response may be influenced by higher levels of LPS translocated to the blood circulation.2-MECHANISM OF OXIDATIVE STRESS IN DAIRY COWS WITH INDUCED SUBACUTE RUMINAL ACIDOSIS.The aims of this study were to investigate the effect of high grain diet on signal transduction which has an influence on antioxidant status.Twelve holstein-friesian cows their weight averaged between 455 ± 28 kg were separated into two groups and assigned to two diets for 18 weeks.The first group was assigned to low-grain(forage-to-concentrate ratio = 6:4)and the second group was assigned to a high-grain(forage-to-concentrate ratio= 4:6)diet based on dry matter.The study showed that feeding a high grain diet was significantly decrease rumen pH,increase lipopolysaccharide concentrations in the rumen fluid and portal vein plasma,hepatic vein plasma,and jugular vein plasma.In addition to that,the malondialdehyde(MDA)was also increased,and total Antioxidants was decreased in cows fed high grain compared to those fed low grain diet.Quantitative real-time PCR result showed increased expression of NOX2,P38,and ERK-1in both the liver and rumen epithelial tissue of cows fed a high grain diet.MCP-1 showed the difference in the liver.However,MCP-1 and ERK-2 mRNA expression in the rumen epithelial did not show any significant difference between HG and LG fed cows.JNK-1 and JNK2 were significantly increased in the rumen epithelium in HG diet versus LG Conversely,these genes were not changed in the liver of cows fed HG diet.The western blotting analysis was used to detect the protein,the phosphorylation levels of nuclear factor-kappa B(pp65),total protein of NF-kB(p65),p38 MAPK and pp38 MAPK were significantly increased in the liver and rumen epithelium of cows fed high grain compared to those fed low grain diet.These results indicate that feeding a high grain diet to the med-lactation dairy cow for a long period result in signaling of both NF-kB and MAPK pathways led to an enhanced oxidative stress response.3-SODIUM BUTYRATE IMPROVES ANTIOXIDANT STABILITY IN SUB-ACUTE RUMINAL ACIDOSIS IN DAIRY GOATS.Currently,little information is known about the effect of sodium butyrate(NaB)on oxidative stress following grain-induced subacute ruminal acidosis in dairy goats.In the present study,18 lactating dairy goats implanted with a ruminal cannula and permanent indwelling catheters in the portal and hepatic veins were randomly allocated into 3 treatment groups over 20 weeks:low grain(LG,40%grain;n = 6),high grain(HG,60%grain;n = 6)and high grain with sodium butyrate(HG + NaB,60%grain + NaB;n = 6).When added to the HG diet,NaB increased the mean ruminal pH and reduced the levels of ruminal,portal and hepatic LPS.Additionally,an increase was also observed in SOD1,SOD2,SOD3,GPX1 and CAT mRNA expression,increased levels of TSOD and CAT enzyme activity as well as increased total antioxidant capacity(T-AOC)and decreased malondialdehyde(MDA)in both the liver and plasma,while GPx activity increased in the liver of goats fed the HG + NaB diet.The mRNA abundance of UGT1A1,NQO1,MGST3,and Nrf2,in addition to total Nrf2 protein levels,was increased in goats fed the HG + NaB diet.Our study indicates that sodium butyrate could improve the oxidative status in sub-acute ruminal acidosis through the partial activation of Nrf2-dependent genes.