Olmesartan niosomes ameliorates the Indomethacin-induced gastric ulcer in rats: Insights on MAPK and Nrf2/HO-1 signaling pathway.
Pharm Res
; 38(11): 1821-1838, 2021 Nov.
Article
en En
| MEDLINE
| ID: mdl-34853982
ABSTRACT
AIMS:
Gastric ulcer is a continuous worldwide threat that inquires protective agents. Olmesartan (OLM) has potent anti-oxidant and anti-inflammatory characters, yet having limited bioavailability. We targeted the gastro-protective potential and probable mechanism of OLM and its niosomal form against indomethacin (IND) induced-gastric ulcer in rats. MAINMETHODS:
we prepared OLM niosomes (OLM-NIO) with different surfactant cholesterol molar ratios. We evaluated particle size, zeta-potential, polydispersity, and entrapment efficiency. In-vitro release study, Fourier transform infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy were performed for selected niosomes. In-vivo, we used oral Omeprazole (30 mg/kg), OLM or OLM-NIO (10 mg/kg) for 3 days before IND (25 mg/kg) ingestion. We assessed gastric lesions, oxidative and inflammatory markers. KEYFINDINGS:
OLM-NIO prepared with span 60cholesterol ratio (11) showed high entrapment efficiency 93 ± 2%, small particle size 159.3 ± 6.8 nm, low polydispersity 0.229 ± 0.009, and high zeta-potential -35.3 ± 1.2 mV, with sustained release mechanism by release data. In-vivo macroscopical and histological results showed gastro-protective effects of OLM pretreatment, which improved oxidative stress parameters and enhanced the gastric mucosal cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) contents. OLM pretreatment suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contents and translocation of p38 mitogen-activated protein kinase (p38-MAPK). Besides, OLM substantially promoted the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) protective pathway. OLM-NIO furtherly improved all previous outcomes.SIGNIFICANCE:
We explored OLM anti-ulcerative effects, implicating oxidative stress and inflammation improvement, mediated by the Nrf2/HO-1 signaling pathway and p38-MAPK translocation. Meanwhile, the more bioavailable OLM-NIO achieved better gastro-protective effects compared to conventional OLM form.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Úlcera Gástrica
/
Tetrazoles
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Antiinflamatorios no Esteroideos
/
Indometacina
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Bloqueadores del Receptor Tipo 1 de Angiotensina II
/
Imidazoles
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Pharm Res
Año:
2021
Tipo del documento:
Article
País de afiliación:
Egipto