Hydrogen peroxide-induced oxidative stress activates NF-κB and Nrf2/Keap1 signals and triggers autophagy in piglets

Abstract

In various pathological conditions of tissue injury, oxidative stress is often associated with autophagy. However, H₂O₂-induced oxidative stress initiates autophagy and its molecular mechanism is still obscure. Here we report that intragastric and peritoneal administration of H₂O₂ caused different degrees of oxidative stress and changed intestinal permeability, morphology, and barrier function in piglets. Western blotting studies revealed that H₂O₂ increased the autophagosome-related protein LC3-I and LC3-II abundance and the ratio of LC3-II to LC3-I content after exposure to 10% H₂O₂ in the jejunum. Meanwhile, the data from beclin1 also indicated that H₂O₂ initiated autophagy in response to oxidative stress. In addition, H₂O₂ activates the NF-κB and Nrf2/Keap1 signals, which may be involved in H₂O₂-induced autophagy. In conclusion, administration of H₂O₂ caused intestinal oxidative stress and triggered an autophagic response, which might be associated with NF-κB and Nrf2/Keap1 signals.