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Whether ɑ-ketoglutarate Administration could Prevent Piglets Oxidative Stress by Regulating CAR and Nrf2 Signaling?

Stress factors during the development of piglets (i.e. birth and weaning processes, inflammation, mycotoxins contamination, and infection) can induce oxidative injury in piglets, which further causes huge economic losses in the intensive pig industry.

Various nutrients have been demonstrated to exhibit antioxidant effect, such as amino acids, polyphenol plant extracts, antimicrobial peptides, and protease.

Recently, ɑ-ketoglutarate (AKG), as a precursor of glutamate and glutamine synthesis, has been shown to protect different animal models against oxidative stress effectively.

However, the mechanisms of antioxidant function regulated by AKG have not been well understood.

Researchers in the Institute of Subtropical Agriculture (ISA) of the Chinese Academy of Sciences conducted to explore the effects of AKG administration on the regulation of constitutive androstane receptor (CAR)-mediated detoxication pathway and nuclear factor erythroid 2–related factor 2 (Nrf2)-associated antioxidant pathway under piglet oxidative stress conditions.

The team found that AKG treatment not only significantly increased the levels of AKG but also that of some amino acids.

Further, there was an increase in α-ketoglutarate dehydrogenase mRNA levels in enterocytes, and a simultaneous reduction in reduced reactive oxygen species (ROS) levels.
Moreover, AKG treatment increased the activities of the antioxidant enzymes and efficiency of cellular respiration.

In addition, AKG also regulated the key target gene and protein expression levels of the CAR- and Nrf2- mediated pathway involved in antioxidant responses and xenobiotic detoxification in vivo and in vitro.

"Our findings suggest that AKG administration has the potential to be useful in the reduction of oxidative stress via activating CAR signaling and modulating cellular respiration and antioxidant capacity." said ZHOU Xihong, a researcher in ISA.

 The study entitled “Prevention of oxidative stress by α?Ketoglutarate via activation of CAR signaling and modulation of the expression of key antioxidant associated targets in vivo and in vitro” was published in journal of agricultural and food chemistry. It was supported by the NationalNatural Science Foundation of China. Details can be found in https://pubs.acs.org/doi/10.1021/acs.jafc.8b04470

Contact:ZHOU Xihong

Email: xhzhou@isa.ac.cn

Institute of Subtropical Agriculture, The Chinese Academy of Science


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