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Adelmidrol, a palmitoylethanolamide analogue, reduces chronic inflammation in a carrageenin-granuloma model in rats.

De Filippis D, D'Amico A, Cinelli MP, Esposito G, Di Marzo V, Iuvone T - J. Cell. Mol. Med. (2008)

Bottom Line: Our results show that the local administration of the compound under study significantly decreases weight and neo-angiogenesis in granulomatous tissue.The anti-inflammatory effect was due to the modulation of mast cells degranulation, as shown by histological analysis and by the inhibition of the release of several pro-inflammatory and pro-angiogenic enzymes (e.g. iNOS, chymase and metalloproteinase MMP-9), and mediators (e.g. nitric oxide and TNF-alpha).The results indicate that adelmidrol, given locally, may represent a potential therapeutic tool in controlling chronic inflammation.

View Article: PubMed Central - PubMed

Affiliation: Università"Federico II", Napoles, Italy.

ABSTRACT
Palmitoylethanolamide (PEA) and some of its analogues have shown great efficacy in the treatment of pain and inflammation. Adelmidrol - the International Nonproprietary Name (INN) of the di-amide derivative of azelaic acid - is one of these analogues. The anti-inflammatory and analgesic effects of PEA and adelmidrol are hypothesized to be mediated, at least in part, by mast cell down-modulation. Mast cell mediators released at early stage of the inflammatory process drive the inflammatory reaction to chronicity as it happens in X-carrageenin-induced granulomatous tissue formation. In the present study, the choice of testing adelmidrol depends upon the physicochemical properties of the compound, i.e. the amphipatic feature, that make it more easily soluble than PEA. In this study, we investigated the effect of adelmidrol on granuloma formation induced by lambda-carrageenin-soaked sponge implant in rats. Our results show that the local administration of the compound under study significantly decreases weight and neo-angiogenesis in granulomatous tissue. The anti-inflammatory effect was due to the modulation of mast cells degranulation, as shown by histological analysis and by the inhibition of the release of several pro-inflammatory and pro-angiogenic enzymes (e.g. iNOS, chymase and metalloproteinase MMP-9), and mediators (e.g. nitric oxide and TNF-alpha). The results indicate that adelmidrol, given locally, may represent a potential therapeutic tool in controlling chronic inflammation.

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Effect of adelmidrol on λ-carrageenin-induced mast cell activation. (A) Mast cell degranulation was evaluated on microscopically visible connective mast cells stained with 0.05% (w/v) toluidine blue and counterstained with 0.1% (w/v) nuclear fast red (magnification 100×). A differentiation between not degranulated (deep blue) and degranulated (light blue) mast cell was valuable. In (B) is shown the counting of mast cell number. Representative Western blot analysis and relative densitometric analysis of (C) Chymase and (D) MMP-9. Tubulin expression is shown as control. Data are representative of 3 separate experiments. Results are expressed as mean ± S.E.M. of 3 experiments; *P < 0.05, **P < 0.01, ***P < 0.001 versus saline; °P < 0.05, °°P < 0.01, °°°P < 0.001 versusλ-carrageenin alone.
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fig04: Effect of adelmidrol on λ-carrageenin-induced mast cell activation. (A) Mast cell degranulation was evaluated on microscopically visible connective mast cells stained with 0.05% (w/v) toluidine blue and counterstained with 0.1% (w/v) nuclear fast red (magnification 100×). A differentiation between not degranulated (deep blue) and degranulated (light blue) mast cell was valuable. In (B) is shown the counting of mast cell number. Representative Western blot analysis and relative densitometric analysis of (C) Chymase and (D) MMP-9. Tubulin expression is shown as control. Data are representative of 3 separate experiments. Results are expressed as mean ± S.E.M. of 3 experiments; *P < 0.05, **P < 0.01, ***P < 0.001 versus saline; °P < 0.05, °°P < 0.01, °°°P < 0.001 versusλ-carrageenin alone.

Mentions: Fig. 4A shows the toluidine blue stained granulomatous tissue sections. Treatment with λ-carrageenin (b) induced a significant mast cell degranulation (light blue stained cells, i.e. degranulated cells, in comparison to the deep blue stained cells, i.e. non-degranulated mast cells); moreover, histological analyses showed that mast cells are predominantly located in close proximity to blood vessels. Adelmidrol (c) was able to reduce mast cell degranulation. Moreover, histological analysis of granulomatous tissue showed that adelmidrol (70 mg/ml), locally administered at time 0, reduced the number of mast cells by 52% (P < 0.001) in comparison to carrageenin alone (104.66 ± 1.67 number of mast cells P < 0.001 versus saline) (Fig. 4B).


Adelmidrol, a palmitoylethanolamide analogue, reduces chronic inflammation in a carrageenin-granuloma model in rats.

De Filippis D, D'Amico A, Cinelli MP, Esposito G, Di Marzo V, Iuvone T - J. Cell. Mol. Med. (2008)

Effect of adelmidrol on λ-carrageenin-induced mast cell activation. (A) Mast cell degranulation was evaluated on microscopically visible connective mast cells stained with 0.05% (w/v) toluidine blue and counterstained with 0.1% (w/v) nuclear fast red (magnification 100×). A differentiation between not degranulated (deep blue) and degranulated (light blue) mast cell was valuable. In (B) is shown the counting of mast cell number. Representative Western blot analysis and relative densitometric analysis of (C) Chymase and (D) MMP-9. Tubulin expression is shown as control. Data are representative of 3 separate experiments. Results are expressed as mean ± S.E.M. of 3 experiments; *P < 0.05, **P < 0.01, ***P < 0.001 versus saline; °P < 0.05, °°P < 0.01, °°°P < 0.001 versusλ-carrageenin alone.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4496105&req=5

fig04: Effect of adelmidrol on λ-carrageenin-induced mast cell activation. (A) Mast cell degranulation was evaluated on microscopically visible connective mast cells stained with 0.05% (w/v) toluidine blue and counterstained with 0.1% (w/v) nuclear fast red (magnification 100×). A differentiation between not degranulated (deep blue) and degranulated (light blue) mast cell was valuable. In (B) is shown the counting of mast cell number. Representative Western blot analysis and relative densitometric analysis of (C) Chymase and (D) MMP-9. Tubulin expression is shown as control. Data are representative of 3 separate experiments. Results are expressed as mean ± S.E.M. of 3 experiments; *P < 0.05, **P < 0.01, ***P < 0.001 versus saline; °P < 0.05, °°P < 0.01, °°°P < 0.001 versusλ-carrageenin alone.
Mentions: Fig. 4A shows the toluidine blue stained granulomatous tissue sections. Treatment with λ-carrageenin (b) induced a significant mast cell degranulation (light blue stained cells, i.e. degranulated cells, in comparison to the deep blue stained cells, i.e. non-degranulated mast cells); moreover, histological analyses showed that mast cells are predominantly located in close proximity to blood vessels. Adelmidrol (c) was able to reduce mast cell degranulation. Moreover, histological analysis of granulomatous tissue showed that adelmidrol (70 mg/ml), locally administered at time 0, reduced the number of mast cells by 52% (P < 0.001) in comparison to carrageenin alone (104.66 ± 1.67 number of mast cells P < 0.001 versus saline) (Fig. 4B).

Bottom Line: Our results show that the local administration of the compound under study significantly decreases weight and neo-angiogenesis in granulomatous tissue.The anti-inflammatory effect was due to the modulation of mast cells degranulation, as shown by histological analysis and by the inhibition of the release of several pro-inflammatory and pro-angiogenic enzymes (e.g. iNOS, chymase and metalloproteinase MMP-9), and mediators (e.g. nitric oxide and TNF-alpha).The results indicate that adelmidrol, given locally, may represent a potential therapeutic tool in controlling chronic inflammation.

View Article: PubMed Central - PubMed

Affiliation: Università"Federico II", Napoles, Italy.

ABSTRACT
Palmitoylethanolamide (PEA) and some of its analogues have shown great efficacy in the treatment of pain and inflammation. Adelmidrol - the International Nonproprietary Name (INN) of the di-amide derivative of azelaic acid - is one of these analogues. The anti-inflammatory and analgesic effects of PEA and adelmidrol are hypothesized to be mediated, at least in part, by mast cell down-modulation. Mast cell mediators released at early stage of the inflammatory process drive the inflammatory reaction to chronicity as it happens in X-carrageenin-induced granulomatous tissue formation. In the present study, the choice of testing adelmidrol depends upon the physicochemical properties of the compound, i.e. the amphipatic feature, that make it more easily soluble than PEA. In this study, we investigated the effect of adelmidrol on granuloma formation induced by lambda-carrageenin-soaked sponge implant in rats. Our results show that the local administration of the compound under study significantly decreases weight and neo-angiogenesis in granulomatous tissue. The anti-inflammatory effect was due to the modulation of mast cells degranulation, as shown by histological analysis and by the inhibition of the release of several pro-inflammatory and pro-angiogenic enzymes (e.g. iNOS, chymase and metalloproteinase MMP-9), and mediators (e.g. nitric oxide and TNF-alpha). The results indicate that adelmidrol, given locally, may represent a potential therapeutic tool in controlling chronic inflammation.

Show MeSH
Related in: MedlinePlus