Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats

Irene Paterniti, Rosanna Di Paola, Michela Campolo, Rosalba Siracusa, Marika Cordaro, Giuseppe Bruschetta, Gemma Tremolada, Anna Maestroni, Francesco Bandello, Emanuela Esposito, Gianpaolo Zerbini, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Although the pathogenesis of diabetic retinopathy (DR) is still insufficiently understood, new evidences indicate 'retinal inflammation' as an important player in the pathogenesis of the complication. Accordingly, common sets of upregulated inflammatory cytokines are found in serum, vitreous and aqueous samples obtained from subjects with DR, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. Thus, based on previously published data, we investigated the effects of Palmitoylethanolamide (PEA), an endogenous lipid amide that belongs to the N-acyl-ethanolamines family, on DR in streptozotocin (STZ)-induced diabetic rats. PEA (10 mg/kg) was administered orally daily starting 3 days after the iv administration of STZ. The rats were killed 15 and 60 day later and eyes were enucleated to evaluate, through immunohistochemical analysis, the key inflammatory events involved in the breakdown of blood retinal barrier (BRB). Immunohistochemical analysis confirmed the presence of VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions in the retina of STZ-treated rats. Of interest, the extent of injury was significantly reduced after treatment with PEA. Altogether, this study provides the first evidence that PEA attenuates the degree of inflammation while preserving the blood-retinal barrier in rats with experimental DR.

Original languageEnglish
Pages (from-to)313-323
Number of pages11
JournalEuropean Journal of Pharmacology
Volume769
DOIs
Publication statusPublished - Dec 15 2015

Fingerprint

Diabetic Retinopathy
Streptozocin
Blood-Retinal Barrier
Inflammation
Ethanolamines
Cytokines
Peroxynitrous Acid
Tight Junctions
Intercellular Adhesion Molecule-1
Amides
Vascular Endothelial Growth Factor A
Retina
Lipids
palmidrol
Wounds and Injuries
Serum

Keywords

  • Diabetic retinopathy
  • Inflammation
  • Palmitoylethanolamide
  • Streptozotocin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Paterniti, I., Di Paola, R., Campolo, M., Siracusa, R., Cordaro, M., Bruschetta, G., ... Cuzzocrea, S. (2015). Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats. European Journal of Pharmacology, 769, 313-323. https://doi.org/10.1016/j.ejphar.2015.11.035

Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats. / Paterniti, Irene; Di Paola, Rosanna; Campolo, Michela; Siracusa, Rosalba; Cordaro, Marika; Bruschetta, Giuseppe; Tremolada, Gemma; Maestroni, Anna; Bandello, Francesco; Esposito, Emanuela; Zerbini, Gianpaolo; Cuzzocrea, Salvatore.

In: European Journal of Pharmacology, Vol. 769, 15.12.2015, p. 313-323.

Research output: Contribution to journalArticle

Paterniti, I, Di Paola, R, Campolo, M, Siracusa, R, Cordaro, M, Bruschetta, G, Tremolada, G, Maestroni, A, Bandello, F, Esposito, E, Zerbini, G & Cuzzocrea, S 2015, 'Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats', European Journal of Pharmacology, vol. 769, pp. 313-323. https://doi.org/10.1016/j.ejphar.2015.11.035
Paterniti, Irene ; Di Paola, Rosanna ; Campolo, Michela ; Siracusa, Rosalba ; Cordaro, Marika ; Bruschetta, Giuseppe ; Tremolada, Gemma ; Maestroni, Anna ; Bandello, Francesco ; Esposito, Emanuela ; Zerbini, Gianpaolo ; Cuzzocrea, Salvatore. / Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats. In: European Journal of Pharmacology. 2015 ; Vol. 769. pp. 313-323.
@article{413d516941bd4156af7838e247644025,
title = "Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats",
abstract = "Although the pathogenesis of diabetic retinopathy (DR) is still insufficiently understood, new evidences indicate 'retinal inflammation' as an important player in the pathogenesis of the complication. Accordingly, common sets of upregulated inflammatory cytokines are found in serum, vitreous and aqueous samples obtained from subjects with DR, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. Thus, based on previously published data, we investigated the effects of Palmitoylethanolamide (PEA), an endogenous lipid amide that belongs to the N-acyl-ethanolamines family, on DR in streptozotocin (STZ)-induced diabetic rats. PEA (10 mg/kg) was administered orally daily starting 3 days after the iv administration of STZ. The rats were killed 15 and 60 day later and eyes were enucleated to evaluate, through immunohistochemical analysis, the key inflammatory events involved in the breakdown of blood retinal barrier (BRB). Immunohistochemical analysis confirmed the presence of VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions in the retina of STZ-treated rats. Of interest, the extent of injury was significantly reduced after treatment with PEA. Altogether, this study provides the first evidence that PEA attenuates the degree of inflammation while preserving the blood-retinal barrier in rats with experimental DR.",
keywords = "Diabetic retinopathy, Inflammation, Palmitoylethanolamide, Streptozotocin",
author = "Irene Paterniti and {Di Paola}, Rosanna and Michela Campolo and Rosalba Siracusa and Marika Cordaro and Giuseppe Bruschetta and Gemma Tremolada and Anna Maestroni and Francesco Bandello and Emanuela Esposito and Gianpaolo Zerbini and Salvatore Cuzzocrea",
year = "2015",
month = "12",
day = "15",
doi = "10.1016/j.ejphar.2015.11.035",
language = "English",
volume = "769",
pages = "313--323",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

TY - JOUR

T1 - Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats

AU - Paterniti, Irene

AU - Di Paola, Rosanna

AU - Campolo, Michela

AU - Siracusa, Rosalba

AU - Cordaro, Marika

AU - Bruschetta, Giuseppe

AU - Tremolada, Gemma

AU - Maestroni, Anna

AU - Bandello, Francesco

AU - Esposito, Emanuela

AU - Zerbini, Gianpaolo

AU - Cuzzocrea, Salvatore

PY - 2015/12/15

Y1 - 2015/12/15

N2 - Although the pathogenesis of diabetic retinopathy (DR) is still insufficiently understood, new evidences indicate 'retinal inflammation' as an important player in the pathogenesis of the complication. Accordingly, common sets of upregulated inflammatory cytokines are found in serum, vitreous and aqueous samples obtained from subjects with DR, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. Thus, based on previously published data, we investigated the effects of Palmitoylethanolamide (PEA), an endogenous lipid amide that belongs to the N-acyl-ethanolamines family, on DR in streptozotocin (STZ)-induced diabetic rats. PEA (10 mg/kg) was administered orally daily starting 3 days after the iv administration of STZ. The rats were killed 15 and 60 day later and eyes were enucleated to evaluate, through immunohistochemical analysis, the key inflammatory events involved in the breakdown of blood retinal barrier (BRB). Immunohistochemical analysis confirmed the presence of VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions in the retina of STZ-treated rats. Of interest, the extent of injury was significantly reduced after treatment with PEA. Altogether, this study provides the first evidence that PEA attenuates the degree of inflammation while preserving the blood-retinal barrier in rats with experimental DR.

AB - Although the pathogenesis of diabetic retinopathy (DR) is still insufficiently understood, new evidences indicate 'retinal inflammation' as an important player in the pathogenesis of the complication. Accordingly, common sets of upregulated inflammatory cytokines are found in serum, vitreous and aqueous samples obtained from subjects with DR, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. Thus, based on previously published data, we investigated the effects of Palmitoylethanolamide (PEA), an endogenous lipid amide that belongs to the N-acyl-ethanolamines family, on DR in streptozotocin (STZ)-induced diabetic rats. PEA (10 mg/kg) was administered orally daily starting 3 days after the iv administration of STZ. The rats were killed 15 and 60 day later and eyes were enucleated to evaluate, through immunohistochemical analysis, the key inflammatory events involved in the breakdown of blood retinal barrier (BRB). Immunohistochemical analysis confirmed the presence of VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions in the retina of STZ-treated rats. Of interest, the extent of injury was significantly reduced after treatment with PEA. Altogether, this study provides the first evidence that PEA attenuates the degree of inflammation while preserving the blood-retinal barrier in rats with experimental DR.

KW - Diabetic retinopathy

KW - Inflammation

KW - Palmitoylethanolamide

KW - Streptozotocin

UR - http://www.scopus.com/inward/record.url?scp=84949035546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949035546&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2015.11.035

DO - 10.1016/j.ejphar.2015.11.035

M3 - Article

C2 - 26607470

AN - SCOPUS:84949035546

VL - 769

SP - 313

EP - 323

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -