1. Effect of melatonin on attenuating the isoflurane-induced oxidative damage is related to PKCα/Nrf2 signaling pathway in developing rats.
- Author
-
Li B, Feng XJ, Hu XY, Chen YP, Sha JC, Zhang HY, and Fan HG
- Subjects
- Animals, Antioxidants pharmacology, Female, Glutathione metabolism, Hippocampus drug effects, Isoflurane pharmacology, Male, Malondialdehyde metabolism, Melatonin metabolism, NF-E2-Related Factor 2 drug effects, NF-E2-Related Factor 2 metabolism, Neuroprotective Agents pharmacology, Oxidation-Reduction drug effects, Oxidative Stress drug effects, Pregnancy, Protein Kinase C-alpha drug effects, Protein Kinase C-alpha metabolism, Rats, Rats, Wistar, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Superoxide Dismutase metabolism, Melatonin pharmacology
- Abstract
Isoflurane, an inhalational anesthesia, has frequently been used in pediatric anesthesia. However, research indicates that isoflurane can induce oxidative stress and affect neural and cognitive development. Melatonin, an endogenous hormone that exhibits antioxidant functions, can play a neuroprotective role by activating the PKCα/Nrf2 signaling pathway in response to oxidative stress. This study aims to determine whether the effect of melatonin on isoflurane-induced oxidative stress is related to activation of the PKCα/Nrf2 signaling pathway. Rat pups at postnatal day 7 were treated with control or 1.5% isoflurane for 4 h after pretreatment for 15 min with either melatonin (10 mg/kg i.p.) or 1% ethanol. The hematoxylin and eosin staining and transmission electron microscopic examination were used for observation of histopathology. The oxidative stress-related indicators were detected by using assay kits. The western blotting, immunohistochemistry and immunofluorescence were used to detect the activation of PKCα/Nrf2 signaling pathway. Results showed that isoflurane induced nerve damage in the hippocampus, and melatonin could reduce this injury. Oxidative stress-related indicators suggested that isoflurane can significantly increase reactive oxygen species and malondialdehyde levels, and decrease superoxide dismutase and glutathione activity compared with the control group, whereas melatonin ameliorated these indices. Expression of proteins associated with the PKCα/Nrf2 signaling pathway indicated that the neuroprotective effect of melatonin is related to activation of the PKCα/Nrf2 signaling pathway. These results suggest that the attenuating effect of melatonin on isoflurane-induced oxidative stress is related to activation of the PKCα/Nrf2 signaling pathway. These findings promote further research into underlying mechanisms and effective treatments to attenuate anesthesia neurotoxicity., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF