NSAIDs are promising agents for preventing cold injury (frigoprotectors). The influence of prophylactic administration of the non-selective COX inhibitor diclofenac sodium (7 mg/kg) and the highly selective COX-2 inhibitor etoricoxib (5 mg/kg) on cyclooxygenase pathway biomarkers was studied on the model of acute general cooling (air hypothermia at -18 °С for 2 hours). Diclofenac completely prevented a decrease in body temperature, surpassing etoricoxib. In the liver of the rats immediately after cold exposure, the content of COX-1 was increased moderately and the content of COX-2 highly significantly. Very significantly, the level of PGE2 decreased, and the levels of PGF2α, especially PGI2 and TXB2, were elevated. In the blood serum, the level of COX-1 was decreased, and the changes in COX-2 and prostaglandins levels were similar to those in the liver. Diclofenac exerted a moderate effect towards the normalization of both COX isoforms in the liver, moderately increased the content of PGE2, and decreased - PGF2α and TXB2 without changing the level of PGI2. In serum, diclofenac reduced COX-1 level to subnormal values, and its effect on other biomarkers was similar to that in the liver, except for a moderate decrease in PGI2. Thus, diclofenac was inferior to etoricoxib, which normalized COX-1, COX-2, PGE2, and PGI2 in the liver and reduced the content of PGF2α and TXB2 in the liver to subnormal values. At the same time, in the blood serum, it decreased COX-1, COX-2, and PGE2 to subnormal values, normalized PGF2α, and PGI2, and significantly reduced TXB2. The opposite degree of intensity of the influence of diclofenac and etoricoxib on the cyclooxygenase pathway and body temperature indicates a dissociation of anti-inflammatory and frigoprotective activity. Inhibition of oxidative stress is not determinative for the frigoprotective activity of NSAIDs since diclofenac, despite the weaker influence on the content of 8-isoprostane in the liver, still exerts the maximum frigoprotective activity.
- Klíčová slova
- Body temperature, body temperature, cold injury prevention, cyclooxygenase, diclofenac sodium, etoricoxib, frigoprotective activity, prostaglandins,
- MeSH
- antiflogistika nesteroidní farmakologie MeSH
- cyklooxygenasa 2 MeSH
- diklofenak farmakologie MeSH
- dinoprost MeSH
- dinoproston MeSH
- etoricoxib MeSH
- hypotermie * MeSH
- krysa rodu Rattus MeSH
- kyselina arachidonová MeSH
- tělesná teplota MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- cyklooxygenasa 2 MeSH
- diklofenak MeSH
- dinoprost MeSH
- dinoproston MeSH
- etoricoxib MeSH
- kyselina arachidonová MeSH
OBJECTIVES: There is good evidence that opioids can potentiate analgesic activity of some older non-opioid analgesics (such as paracetamol or ibuprofen) but it is not known whether this also holds true for newer non-opioid analgesics that selectively inhibit cyclooxygenase 2 (coxibs). This study was undertaken to determine the nature of the interaction between codeine and celecoxib or etoricoxib in peritoneal irritation-induced visceral pain in mice. For comparison, interactions of codeine with paracetamol and ibuprofen were also tested using the same method. MATERIAL AND METHODS: A small volume of a weak acetic acid (0.6%) was injected into the peritoneal cavity and the number of writhes (contractions of abdominal muscles) was counted. All drugs were given orally. Their interaction was characterized using isobolographic analysis. RESULTS: Codeine, etoricoxib, celecoxib, ibuprofen and paracetamol all independently produced dose-dependent suppression of writhing. The isobolographic analysis carried out using equipotent dose ratios showed that the interactions between codeine and etoricoxib or celecoxib were sub-additive or additive, respectively. This was in contrast to combinations of codeine with ibuprofen or paracetamol, which were supra-additive. Interaction indexes γ, determined as a ratio between experimental and theoretical ED50 values of the mixture, were as follows: 2.7 for codeine + etoricoxib, 0.62 for codeine + celecoxib, 0.43 for codeine + ibuprofen and 0.33 for codeine + paracetamol. CONCLUSIONS: These and other results suggest that opioids do not seem to potentiate analgesic effects of selective COX-2 inhibitors, in contrast to nonselective COX inhibitors or paracetamol.
- MeSH
- bolest chemicky indukované farmakoterapie MeSH
- celekoxib MeSH
- etoricoxib MeSH
- ibuprofen terapeutické užití MeSH
- inbrední kmeny myší MeSH
- inhibitory cyklooxygenasy 2 terapeutické užití MeSH
- interpretace statistických dat MeSH
- kodein terapeutické užití MeSH
- kyselina octová škodlivé účinky MeSH
- lékové interakce MeSH
- modely u zvířat MeSH
- myši MeSH
- neopioidní analgetika terapeutické užití MeSH
- opioidní analgetika terapeutické užití MeSH
- paracetamol terapeutické užití MeSH
- pyrazoly terapeutické užití MeSH
- pyridiny terapeutické užití MeSH
- regresní analýza MeSH
- sulfonamidy terapeutické užití MeSH
- sulfony terapeutické užití MeSH
- synergismus léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- celekoxib MeSH
- etoricoxib MeSH
- ibuprofen MeSH
- inhibitory cyklooxygenasy 2 MeSH
- kodein MeSH
- kyselina octová MeSH
- neopioidní analgetika MeSH
- opioidní analgetika MeSH
- paracetamol MeSH
- pyrazoly MeSH
- pyridiny MeSH
- sulfonamidy MeSH
- sulfony MeSH
We investigated the role of prostaglandin E2 in reptilian regeneration. Prostaglandin E2 is known to play a vital role during wound healing and cell proliferation. A significant delay in the rate of growth of regenerate after autotomy was observed when the production of prostaglandin E2 was blocked by usage of specific cyclooxygenase inhibitors as compared to control animals and this delay continued to all the defined stages of regeneration. Therefore, prostaglandin E2 could be one of the essential requirements for a successful process of regeneration.
- MeSH
- celekoxib MeSH
- cyklooxygenasa 2 biosyntéza MeSH
- dinoproston antagonisté a inhibitory fyziologie MeSH
- etoricoxib MeSH
- inhibitory cyklooxygenasy farmakologie MeSH
- ještěři fyziologie MeSH
- ocas účinky léků fyziologie MeSH
- pyrazoly farmakologie MeSH
- pyridiny farmakologie MeSH
- regenerace účinky léků fyziologie MeSH
- sulfonamidy farmakologie MeSH
- sulfony farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- celekoxib MeSH
- cyklooxygenasa 2 MeSH
- dinoproston MeSH
- etoricoxib MeSH
- inhibitory cyklooxygenasy MeSH
- pyrazoly MeSH
- pyridiny MeSH
- sulfonamidy MeSH
- sulfony MeSH
