Lipopolysaccharide induces oxidative stress by triggering MAPK and Nrf2 signalling pathways in mammary glands of dairy cows fed a high-concentrate diet

Abstract

The goal of current investigations was to reveal the molecular mechanism triggered through feeding a diet with high-concentrate to dairy cows for subacute ruminal acidosis (SARA) induction and to examine the oxidative stress parameters in their mammary epithelial tissue. In an eighteen-weeks feeding trial, 12 Holstein Friesian cows with a standard weight of 455 ± 28 kg were evenly divided into two groups and given either a low-concentrate (LC, forage to concentrate ratio = 6:4) or a high-concentrate (HC, forage to concentrate ratio = 4:6) diet. A remarkable reduction in ruminal pH also increased ruminal lipopolysaccharide (LPS) concentration that was observed in the high-concentrate group of cows at 4 h post-feeding in the morning. Moreover, reduced milk yield was observed in the HC group. The relative mRNA abundance of glutathione peroxidase (GPX) 1 and 3 and superoxide dismutase (SOD) 1 and 2 were down-regulated in high-concentrate fed animals than in the LC, while mRNA was expressed with no change in the of SOD3 among groups. In addition, genes responsible for oxidative stress e.g., ERK, JNK, and p38 were also showed dramatically high mRNA intensity in HC group. The protein concentration of ERK, pERK, pJNK, with pp38, were up-regulated significantly as JNK & p38 showed no big difference. While Nrf2 and pNrf2 were down-regulated considerably in HC group. The total antioxidant capacity (T-AOC) was significantly decreased but of Malondialdehyde (MDA) concentration was raised in HC group than in LC. We thus proposed that higher levels of endogenous LPS may affect the Mitogen-activated protein kinases (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent antioxidant response.