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Objective: The present study aimed to see if 20-Deoxyingenol(20-DOI) could protect hippocampus neurons from the neurotoxic effects of morphine and reduce memory loss in rats. Method: Male Wistar rats were given morphine hydrochloride (45 mg/kg, sc, four weeks) and 20-DOI (10, 20 mg/kg, ip., coadministered with morphine) for the Morris Water Maze (MWM) test to investigate the effects of 20-DOI on spatial learning and memory. Western blotting was used to evaluate the expression of the hippocampal CA1 region of the cleaved caspase-3, Bax, and Bcl2 proteins and so on. Moreover, these assays were used to evaluate the expression of superoxide dismutase (SOD)2, heme oxygenase 1(HO1) protein, and glutathione peroxidase (GPx) activity within the hippocampus CA1 area. Results: The administration of 20-DOI (10 and 20 mg/kg) to morphine-treated mice enhanced spatial learning and reduced memory deficits. Additionally, 20-DOI treatment reduced apoptosis and oxidative stress in the hippocampal CA1 region of morphine-treated rats. Moreover, 20-DOI improved the autophagy level of the hippocampal CA1 area of morphine-treated rats using Transcription factor EB (TFEB), and 20-DOI prevented spatial learning and memory impairment in morphine-treated rats. The current observation could be partially due to the inhibition of neuronal apoptosis and oxidative stress in the hippocampal CA1 region of rats treated with morphine and the improved autophagy in this region. Conclusions: 20-DOI attenuated morphine administration in rats with chronic disease caused spatial learning and memory dysfunction. These mechanistic effects could be partially related to 20-DOI protecting the CA1 region of rat hippocampal neurons from the morphine-induced oxidative stress, apoptosis, and autophagy through TFEB.
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Background: As a class of analgesics, opioids are frequently used to treat both acute and chronic moderate to severe pain. Patients frequently receive opioid painkillers after orthopedic accidents or surgeries. Evidence suggests that opioid drug users have a 55.1% higher risk of fracture and poor bone repair than non-users of opioid drugs. The key pathogenic alterations in the incidence and progression of poor bone repair are over apoptosis and aging of osteoblasts due to the stress caused by oxidation. Dexmedetomidine (Dex) has been proven to protect against a variety of degenerative illnesses by reducing oxidative stress. However, nothing is known about how it affects bone repair. Methods: PI3K/Akt/Nrf2 pathway was detected by immunofluorescence and Western blot. SOD, CAT, JC-1, dihydroethidium and mitosox were used in the Oxidative Stress. Micro-CT, H&E and Masson's staining, immunohistochemically were performed to evaluate the therapeutic effects of DEX on calvarial defects in the morphine-induced rat model. Results: We found that morphine-induced an imbalance in the metabolism and catabolism of primary rat Osteoblasts. However, these conditions could be inhibited by DEX treatment. In the meantime, DEX induced the expression of Nrf2-regulated antioxidant enzymes such as NQO1, HO-1, GCLm, GCLc, and TrxR1. DEX-mediated Nrf2 activation is linked to the PI3K/Akt signaling system. Furthermore, it has been established that intravenous DEX enhanced the growth of bone healing in a model of a surgically produced rat cranial lesion. Conclusion: This is the first description of the unique DEX mechanism acting as a Nrf2 activator against morphine-mediated oxidative harm, raising the possibility that the substance may be used to prevent bone defects.
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Introduction: At present, the mu opioid receptor is the most important neuroaesthetics receptor in anesthesiology research, and the damage that it does to the nervous system is unknown. Methods: We investigated the effects of loperamide, an agonist of the mu opioid receptor, on protein expression in HT22 cells using stable isotope labeling of amino acids in cell culture (SILAC), immobilized metal affinity chromatography (IMAC) enrichment, and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 7,823 proteins were identified. Results and Discussion: Bioinformatic analysis revealed that mu opioid receptor agonism can induce distinct changes in the proteome of HT22 cells. These findings improve our understanding of narcotic drugs.