Oxidative Stress Can Be Attenuated by 4-PBA Caused by High-Fat or Ammonia Nitrogen in Cultured Spotted Seabass: The Mechanism Is Related to Endoplasmic Reticulum Stress

Abstract

Oxidative stress is a common phenomenon in aquaculture, which can be induced by nutritional or environmental factors. Generally, oxidative stress causes poor growth performance, metabolic dysregulation, and even the death of aquatic animals. To identify a nutritional intervention strategy, high-fat diet (HFD) feeding (Experiment I) and acute ammonia nitrogen challenge (Experiment II) tests were carried out. In Experiment I, HFD feeding significantly decreased the growth performance concomitantly with excessive fat deposition in the liver and abdomen. The addition of 4-PBA in the diet improved the excessive fat accumulation. The activities of antioxidative enzymes were suppressed, and the levels of lipid and protein peroxidation were increased, indicating that HFD feeding induced oxidative stress. The endoplasmic reticulum stress (ERs) related genes were downregulated in the HFD group. Under a transmission electron microscope (TEM), more swollen and dilated ER lumen could be observed. These results indicated that the HFD induced ERs activation. Although 4-PBA acted as a potent ERs inhibitor, as evidenced by the alleviated alterations of ERs molecules and the ER ultrastructure, the oxidative stress was also attenuated by 4-PBA. In Experiment II, dietary 4-PBA improved the tolerance to the acute ammonia nitrogen challenge, as lower mortality and serum aminotransferase activity was found. Further results showed that 4-PBA decreased the peroxidation content and attenuated ERs, thus confirming the correlation between oxidative stress and ERs. Our findings showed that dietary 4-PBA supplementation can attenuate oxidative stress induced by a HFD or acute ammonia challenge; the mechanism is related to its potent inhibition effect for ERs.

Inhibition of endoplasmic reticulum stress prevents renal pathology in hindlimb unloaded mice

“…Thus, it is possible that restoration of ER function with 4PBA may also have positive effects on mitochondrial bioenergetics in HU mice. In addition, the direct antioxidant effects of 4PBA may also have assisted in mitochondrial restoration in HU conditions [33].…”

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…Originally used in urea cycle disorders and later in the treatment of cystic fibrosis in the 1990s [300,301], phenylbutyrate has been reported to attenuate ROS production in activated microglia [302]. Additionally, 4-PBA has been found to reduce oxidative stress caused by a high-fat diet or acute ammonia challenge by counteracting ER stress [303]. Furthermore, 4-PBA has shown the ability to decrease ER stress and prevent disease phenotypes in murine glaucoma models [304].…”

Substituting Fish Meal with a Bacteria Protein (Clostridium autoethanogenum Protein) Derived from Industrial-Scale Gas Fermentation: Effects on Growth and Gut Health of Juvenile Large Yellow Croakers (Larimichthys crocea)

“…Blood was drawn from the tail vein according to the method in [19] by using a sterile injector, and serum was separated by centrifuging (850× g, 4 • C, 10 min) and then stored at −80 • C till analysis. The liver and gut were collected for histological and other analysis, in accordance with the method described in our recent study [20].…”