Proanthocyanidins Protect against β-Hydroxybutyrate-Induced Oxidative Damage in Bovine Endometrial Cells.

Xi Cheng,Shuhua Yang,Yi Zhang,Jianbin He,Miao Long,Chuang Xu,Cai Zhang,Lanzhi Li,Peng Li,Yang Guo

doi:10.3390/molecules24030400

Abstract

Metabolic diseases, such as ketosis, are closely associated with decreased reproductive performance (such as delayed estrus and decreased pregnancy rate) in dairy cows. The change of β-hydroxybutyrate (BHBA) concentration in dairy cattle is an important mechanism leading to ketosis, and its blood concentration in ketotic cows is always significantly higher than in nonketotic cows. Many studies indicated that BHBA can induce oxidative damage in liver and other organs. Proanthocyanidins (PCs) have gained substantial attention in the last decade as strong antioxidative substances. This study aimed to demonstrate a protective effect of PCs against BHBA-induced oxidative stress damage in bovine endometrial (BEND) cells by activating the nuclear erythroid2-related factor2 (Nrf2) signaling pathway. Our research show that PCs could significantly increase activities of catalase (CAT) and glutathione peroxidase (GSH-PX), glutathione (GSH) content, and antioxidant capacity (T-AOC), while significantly decreasing malondialdehyde (MDA) content in BEND cells. Both mRNA and protein expression levels of Nrf2 were significantly increased in BEND cells, and glutamate–cysteine ligase catalytic subunit (GCLC), heme oxygenase 1 (HO-1), manganese superoxide dismutase (Mn-SOD), and NAD(P)H quinone dehydrogenase 1 (NQO-1) were also significantly increased. These results indicate that PCs can antagonize BHBA-induced oxidative damage by activating the Nrf2 signaling pathway to exert an antioxidant effect.

Highlights

Ketosis occurring in dairy cows during transition period is associated with the negative energy balance (NEB)
Dairy cows undergo tremendous physiological challenges to the homeostatic mechanisms in the transition period leading to transition stress in the form of increased oxidative stress, reduced immunological capacity, and generation of a negative energy balance (NEB), which results in impaired postpartum fertility [30]
Ketosis in cows is usually accompanied by severe oxidative stress and inflammatory response, which were mainly associated with increased BHBA and nonessential fatty acids (NEFAs)

Summary

Introduction

Ketosis occurring in dairy cows during transition period is associated with the negative energy balance (NEB). The main mechanism of NEB was the reduction of dry matter intake and the increase of energy expenditure in early postpartum period [1]. NEB triggers excessive fat mobilization and increases blood concentrations of nonessential fatty acids (NEFAs). NEFAs are first fully oxidized to provide the energy requirement for the liver. BHBA concentration in blood is always used for diagnosis of ketosis [3]. Many studies have shown that BHBA is associated with energy metabolism, neuroprotection, and ATP production [4], and it can cause oxidative stress, inflammatory response, and even cellular apoptosis, by activating signaling pathways [5,6]. BHBA can efficiently activate the Nrf pathway in classical Keap1-Cys151, and induce pathway activation in a dependent manner [7]

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