In vivo effects of N/OFQ(1–13)NH2 and its structural analogue [ORN9]N/OFQ(1–13)NH2 on carrageenan-induced inflammation: rat-paw oedema and antioxidant status

Zamfirova, R; Tsvetanova, Elina; Alexandrova, Albena; Petrov, Lubomir; Mateeva, Polina; Павлова, А.; Kirkova, Margarita; Todorov, S

doi:10.2478/s11535-009-0006-4

Cited by 8 publications

(6 citation statements)

References 51 publications

(71 reference statements)

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“…The experiments confirmed our previous findings, that N/OFQ(1-13)NH 2 (applied simultaneously with CG) and [Orn 9 ]N/OFQ(1-13)NH 2 (applied 15 min before CG) in a dose of 20 ñg/kg suppress the carrageenan-induced paw-oedema inflammation [ 17 ]. Our observation indicates the potential value of these pep- tides for treatment of pain, oedema, cough, drug dependence, stress-induced anorexia, etc.…”

supporting

confidence: 90%

Involvement of Vanilloid- and Cannabinoid Receptors in the Anti-inflammatory Action of Nociceptin

Mateeva¹,

Zamfirova²

2013

Proceeding BAS

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In the present study, we have examined the probable interactions of N/OFQ(1-13)NH 2 and its structural analogue [Orn 9 ]N/OFQ(1-13)NH 2 with cannabinoid CB 1 -receptors on acute carrageenan (CG)-induced inflammation in rat paw, as well as the mechanism of these interactions. The study also aims to find out whether the TRPV1-receptors (transient receptor potential vanilloid 1) take part in these processes. Our results showed that the simultaneous treatment of rats with CB 1 -receptor agonist HU-210 and the investigated peptides did not change the specific effects of the nociceptin and [Orn 9 ]N/OFQ(1-13)NH 2 . Applied after blockade of CB 1 -receptors, the peptides did not exert their anti-inflammatory effects. On the contrary, when the TRPV1-receptors were blocked, the anti-inflammatory effects of nociceptin (NOP)-receptor agonists as a whole remained unchanged.In conclusion, based on the results obtained, it might be suggested that N/OFQ(1-13)NH 2 and [Orn 9 ]N/OFQ(1-13)NH 2 influenced the peripheral inflammation by interactions with their own NOP-receptors located on the primary sensory neurons.We also suppose that there is a functional link between NOP-and cannabinoid CB 1 -receptors. It might be assumed that vacant or activated CB 1 -receptors are required for NOP-evoked inhibition of acute peripheral inflammation.Key words: nociceptin, rat-paw inflammation, CB 1 -receptorsThe paper is supported by the National Science Fund of the Ministry of Education, Youth and Science of Bulgaria (Grant L-1510/05). 273Introduction. In spite of the various investigations performed over the last years, the pathophysiology of acute peripheral inflammation still remains unclear. This interest is based on the fact that the inflammation usually accompanies many widespread diseases such as asthma, arthritis, colitis, gastritis, etc. The inflammation process is associated with release of many pro-inflammatory mediators by the cutaneous nerve endings, such as substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A, [ 1 ] usually followed by vasodilatation and increased vascular permeability, plasma extravasation, neutrophil infiltration, oedema, etc., in the area innervated by the stimulated nerve [ 2 ]. It has been found that nociceptive primary afferent neurons express both receptor types -NOP and CB 1 . Many data have shown that cannabinoids [ 3, 4 ] as well as nociceptin (N/OFQ) [ 5 ] reduce acute peripheral inflammation by suppressing the release of substance P and CGPR from the primary sensory neurons. Generally, cannabinoids reduce inflammation and hyperalgesia by activating the peripheral CB 1 -receptor. The effects of some CB 1 -agonists are mediated via the TRPV1-receptor [ 6,7 ]. On the other hand, it is worth mentioning that N/OFQ inhibits the effects of the activated 9,5 ].Taken together, literature data suggest common stages in the mechanisms of action of cannabinoids and nociceptin in inflamed tissues and also that the involvement of vanilloid receptors in them is very likely. Therefore, com...

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supporting

confidence: 90%

Involvement of Vanilloid- and Cannabinoid Receptors in the Anti-inflammatory Action of Nociceptin

Mateeva¹,

Zamfirova²

2013

Proceeding BAS

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“…As observed previously [31], these peptides did not change the antioxidant status of the control-and CG-inflamed paw tissues. This agrees with the data published by Trombella et al [59] that N/OFQ stimulates chemotaxis of monocytes (via NOP receptor activation) but not of neutrophils and that this peptide does not affect neutrophil-dependent O 2 -production.…”

supporting

confidence: 85%

“…Using this CG-model of acute inflammation [31], we studied the effects of N/OFQ(1-13)NH 2 and [Orn 9 ]N/OFQ(1-13)NH 2 on antioxidant status of erythrocytes and liver of control and GC-treated animals.…”

Section: Resultsmentioning

confidence: 99%

In-vivo effects of nociceptin and its structural analogue [Orn9] nociceptin on the antioxidant status of rat blood and liver after carrageenan-induced paw inflammation

et al. 2010

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AbstractThe production of reactive oxygen species (ROS) in cells is well balanced with their elimination by the antioxidant defence system. This balance is essential for maintenance of physiological conditions, and its disturbance (oxidative stress) has been suggested as a potential pathogenic mechanism in a variety of diseases, accompanied by inflammation. In this study, the in-vivo effects of nociceptin (N/OFQ(1–13)NH2) and its structure analogue [Orn9]N/OFQ(1–13)NH2 were studied on markers of oxidative stress in erythrocytes and liver of rats 4 hours after subplantar administration of carrageenan (CG) (1%, 100 µl) in the right hind paw. A considerable inflammatory oedema of the paw was observed. CG did not change blood haemoglobin content, hematocrit value, glutathione level and antioxidant enzyme activities in the erythrocytes, but there was an increase in lipid peroxidation. In liver, CG-induced imbalance was manifested by an increase in lipid peroxidation and a decrease in glutathione level. Both peptides (20 µg, i.p.), when administered alone, had no effect on all parameters tested. When either [Orn9]N/OFQ(1–13)NH2 or N/OFQ(1–13)NH2 was injected simultaneously with CG or 15 minutes before it, they did not affect the CG-induced changes in the antioxidant status of the erythrocytes and liver. Our results suggest that the peptides tested did not play a role in the free radical processes that accompany CG-induced paw inflammation.

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“…6,7,[16][17][18] Our previous studies have shown that CG decreases the total glutathione (GSH/GSSG) level and superoxide dismutase activity (Cu,Zn-SOD) and increases the glutathione peroxidase (GPx) and glucose-6-phospate dehydrogenase (Glu-6-P-DH) activities, as measured in post-nuclear homogenate of the inflamed paw. 19 It increases the LPO but does not change the blood haemoglobin content, haematocrit value, GSH/GSSG level and antioxidant enzyme activities in the erythrocytes; CG-induced imbalance in liver is manifested by increased LPO and decreased GSH/ GSSG level. 20 According to Oyanagui,13 superoxide anion radical (O 2 -) participates in the prostaglandin-phase swelling (2-4 h) of , together with peroxynitrite and hydroxyl radical ( • OH) formed with its participation, are of significance for the acute inflammation and inflammatory pain.…”

Section: Introductionmentioning

confidence: 93%

“…CG‐induced local inflammation leads to enhanced metabolism of arachidonic acid; increased levels of malondialdehyde, nitric oxide and prostaglandin E 2 ; increased production of pro‐inflammatory cytokines and decreased GSH level . Our previous studies have shown that CG decreases the total glutathione (GSH/GSSG) level and superoxide dismutase activity (Cu,Zn‐SOD) and increases the glutathione peroxidase (GPx) and glucose‐6‐phospate dehydrogenase (Glu‐6‐P‐DH) activities, as measured in post‐nuclear homogenate of the inflamed paw . It increases the LPO but does not change the blood haemoglobin content, haematocrit value, GSH/GSSG level and antioxidant enzyme activities in the erythrocytes; CG‐induced imbalance in liver is manifested by increased LPO and decreased GSH/GSSG level …”

Section: Introductionmentioning

confidence: 99%

Effects of desipramine on the antioxidant status in rat tissues at carrageenan‐induced paw inflammation

Vircheva

Nenkova

Georgieva

et al. 2011

Cell Biochemistry & Function

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The pathogenesis of many diseases and different pathological conditions, including inflammation, is associated with excess production of reactive oxygen species (ROS). The present study aimed to investigate the effects of the antidepressant desipramine (DES) on carrageenan (CG)-induced inflammation, as well as on the endogenous levels of cell enzyme and non-enzyme antioxidants in rat liver and spleen, 4 and 24 h after CG injection. The intra-plantar CG injection into the right hind paw resulted in a time-dependent increase in the paw volume; the maximum of CG-induced edema peak was in 2-4 h. A single DES dose of 20 mg · kg(-1) , administered 30 min before CG, had no effect on paw edema, whereas the higher drug dose used (50 mg · kg(-1) ) suppressed the edematous response to CG. The latter drug dose protected CG-induced decrease of glutathione (non-enzyme antioxidant) in the liver; it did not affect CG-unchanged activities of superoxide dismutase, glutathione peroxidase (enzyme antioxidants) and glucose-6-phosphate dehydrogenase (enzyme, important for the activity of glutathione-conjugated antioxidant enzymes) in both liver and spleen. The drug showed an efficient antioxidant capacity in ROS-generating chemical systems; it was higher than that of fluoxetine (another type of antidepressant). The present results suggest that the good antioxidant activity of DES might contribute to its beneficial effects in liver injuries.

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In vivo effects of N/OFQ(1–13)NH2 and its structural analogue [ORN9]N/OFQ(1–13)NH2 on carrageenan-induced inflammation: rat-paw oedema and antioxidant status

Cited by 8 publications

References 51 publications

Involvement of Vanilloid- and Cannabinoid Receptors in the Anti-inflammatory Action of Nociceptin

Involvement of Vanilloid- and Cannabinoid Receptors in the Anti-inflammatory Action of Nociceptin

In-vivo effects of nociceptin and its structural analogue [Orn9] nociceptin on the antioxidant status of rat blood and liver after carrageenan-induced paw inflammation

Effects of desipramine on the antioxidant status in rat tissues at carrageenan‐induced paw inflammation

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