Morphine, but not methadone, inhibits microsomal prostaglandin E synthase-1 and prostaglandin-endoperoxide synthase 2 in lipopolysaccharide-stimulated horse synoviocytes.
Abstract: Osteoarthritis (OA) is one of the main locomotor disorders in horses. Although nonsteroidal anti-inflammatory drugs are the first-line treatment for OA, opioids could also be used. In previous studies, opioids showed promising anti-inflammatory and analgesic effects. In this study, we aimed to investigate the effects of two opioids (morphine and methadone) against inflammation in lipopolysaccharide (LPS)-stimulated synoviocytes by analyzing microsomal prostaglandin E synthase-1 (mPGES-1) and prostaglandin-endoperoxide synthase 2 (PTGS2) expression. Synoviocytes were obtained from the joints at the distal limbs of dead animals. The cytotoxic effects of LPS, morphine, and methadone were investigated by using a cell viability assay with crystal violet dye. Synoviocytes were treated with LPS, LPS plus morphine, or LPS plus methadone for 3, 6, and 12 h, and mPGES-1 and PTGS2 expression was measured using real-time polymerase chain reaction. LPS, and morphine did not affect the viability of synoviocytes, even at high concentrations. LPS treatment increased mPGES-1 and PTGS2 expression, whereas morphine inhibited the increase in mPGES-1 and PTGS2 expression in LPS-stimulated synoviocytes. Methadone did not inhibit mPGES-1 or PTGS2 expression. These results suggest that morphine may exhibit anti-inflammatory effect; therefore, it might be beneficial for the treatment of OA.
Copyright © 2019 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.
Publication Date: 2019-02-11 PubMed ID: 30763639DOI: 10.1016/j.biochi.2019.02.004Google Scholar: Lookup
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Summary
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The research investigates the effects of morphine and methadone, types of opioids, on inflammation in horse joint cells, finding that morphine, but not methadone, can reduce an increase in inflammatory markers.
Objective and Background Information
- The primary aim of the study was to explore the impact of two opioids, namely morphine and methadone, on inflammation in lipopolysaccharide-stimulated synoviocytes, which are cells resident in joints, by focusing on microsomal prostaglandin E synthase-1 (mPGES-1) and prostaglandin-endoperoxide synthase 2 (PTGS2) expression.
- As a backdrop to the research, the authors mention that osteoarthritis is among the main locomotor disorders in horses and is commonly treated with nonsteroidal anti-inflammatory drugs. However, recent studies pointed to the potential effectiveness of opioids in anti-inflammatory and analgesic roles.
Methodology
- Synoviocytes were extracted from the distal limb joints of deceased animals for use in the study.
- Using a cell viability assay with crystal violet dye, the researchers checked the cytotoxic effects of lipopolysaccharide (LPS), morphine, and methadone.
- The treatment groups were arranged as follows: synoviocytes treated with only LPS, LPS plus morphine, or LPS plus methadone, for 3, 6, and 12 hours. Afterwards, the levels of mPGES-1 and PTGS2 expression were evaluated using a real-time polymerase chain reaction (PCR) procedure.
Findings
- Results from the cell viability assay showed that both LPS and morphine did not affect the viability of the synoviocytes, even at high concentrations.
- LPS treatment caused an increase in the expression of both mPGES-1 and PTGS2, the molecules implicated in inflammation.
- Morphine was found to inhibit the increase of both mPGES-1 and PTGS2 expression in LPS-stimulated synoviocytes.
- On the other hand, methadone did not have an inhibitory effect on the expression of mPGES-1 or PTGS2.
Implications
- The study’s findings imply that morphine could demonstrate an anti-inflammatory effect since it inhibited the boost in mPGES-1 and PTGS2 expression in inflamed synoviocytes.
- Based on these results, morphine could potentially be useful in treating osteoarthritis, although further studies are needed to confirm this therapeutic role.
Cite This Article
APA
Schwarzbach SV, Melo CF, Xavier PLP, Roballo KC, Cordeiro YG, Ambrósio CE, Fukumasu H, Carregaro AB.
(2019).
Morphine, but not methadone, inhibits microsomal prostaglandin E synthase-1 and prostaglandin-endoperoxide synthase 2 in lipopolysaccharide-stimulated horse synoviocytes.
Biochimie, 160, 28-33.
https://doi.org/10.1016/j.biochi.2019.02.004 Publication
Researcher Affiliations
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.
- Laboratory of Comparative and Translational Oncology (LOCT), Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.
- Innovative Therapies Group (GDTI), Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.
- Laboratory of Comparative and Translational Oncology (LOCT), Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.
- Innovative Therapies Group (GDTI), Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.
- Laboratory of Comparative and Translational Oncology (LOCT), Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.
- Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil. Electronic address: carregaro@usp.br.
MeSH Terms
- Analgesics, Opioid / pharmacology
- Animals
- Cells, Cultured
- Cyclooxygenase 2 / chemistry
- Gene Expression Regulation, Enzymologic / drug effects
- Horses
- Inflammation / chemically induced
- Inflammation / drug therapy
- Inflammation / enzymology
- Lipopolysaccharides / toxicity
- Male
- Methadone / pharmacology
- Microsomes / enzymology
- Morphine / pharmacology
- Prostaglandin-E Synthases / antagonists & inhibitors
- Synoviocytes / drug effects
- Synoviocytes / immunology
- Synoviocytes / metabolism
- Synoviocytes / pathology
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