A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in rats
There are few studies addressing duodenal inflammation. This study was designed to investigate the effects of a recently developed biotechnological product, a nano-formulation of olmesartan medoxomil (OM) - olmesartan medoxomil zeinmersomes (OMZ) - for the treatment of indomethacin-induced duodeniti...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2023-05-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100636&lng=en&tlng=en |
| _version_ | 1797816888463458304 |
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| author | H.A. Murad T.M. Alqurashi |
| author_facet | H.A. Murad T.M. Alqurashi |
| author_sort | H.A. Murad |
| collection | DOAJ |
| description | There are few studies addressing duodenal inflammation. This study was designed to investigate the effects of a recently developed biotechnological product, a nano-formulation of olmesartan medoxomil (OM) - olmesartan medoxomil zeinmersomes (OMZ) - for the treatment of indomethacin-induced duodenitis in rats. Adult male Wistar rats were given indomethacin (10 mg/kg/day) for four weeks. They were divided into a positive control group (PC, untreated) and two groups treated orally with 3 mg/kg per day of OM or OMZ for the last two weeks of the 4-week indomethacin-treatment. At end of the four weeks, blood and duodenum were collected. Duodenal homogenate was used for measurement of levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, reduced glutathione (GSH), and cleaved caspase-3. Duodenal sections were stained with H&E. Gene expressions of nuclear factor kappa B (NF-κB p65), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) by RT-PCR, and protein expression of survivin by western blot were assessed. Plasma and duodenal olmesartan concentrations were measured by high performance liquid chromatography mass spectrometry. The duodenitis rats showed significantly higher duodenal levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and cleaved caspase-3, a significantly lower GSH level, and histopathological alterations. Moreover, they showed upregulated gene expressions of NF-κB p65 and Bax, downregulated gene expression of Bcl-2, decreased Bcl-2/Bax ratio, and lower protein expression of survivin. OMZ was more effective in protecting the duodenum from indomethacin-induced injuries compared to OM due to improved delivery, higher bioavailability, and better anti-inflammatory, antioxidant, and antiapoptotic effects. OMZ could be a better choice for hypertensive patients with non-steroidal anti-inflammatory drugs-induced duodenitis. |
| first_indexed | 2024-03-13T08:44:21Z |
| format | Article |
| id | doaj.art-adee53d481504e35897287e2501e7377 |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-03-13T08:44:21Z |
| publishDate | 2023-05-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-adee53d481504e35897287e2501e73772023-05-30T07:32:49ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2023-05-015610.1590/1414-431x2023e12665A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in ratsH.A. Muradhttps://orcid.org/0000-0002-8406-4946T.M. Alqurashihttps://orcid.org/0000-0003-4466-7432There are few studies addressing duodenal inflammation. This study was designed to investigate the effects of a recently developed biotechnological product, a nano-formulation of olmesartan medoxomil (OM) - olmesartan medoxomil zeinmersomes (OMZ) - for the treatment of indomethacin-induced duodenitis in rats. Adult male Wistar rats were given indomethacin (10 mg/kg/day) for four weeks. They were divided into a positive control group (PC, untreated) and two groups treated orally with 3 mg/kg per day of OM or OMZ for the last two weeks of the 4-week indomethacin-treatment. At end of the four weeks, blood and duodenum were collected. Duodenal homogenate was used for measurement of levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, reduced glutathione (GSH), and cleaved caspase-3. Duodenal sections were stained with H&E. Gene expressions of nuclear factor kappa B (NF-κB p65), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) by RT-PCR, and protein expression of survivin by western blot were assessed. Plasma and duodenal olmesartan concentrations were measured by high performance liquid chromatography mass spectrometry. The duodenitis rats showed significantly higher duodenal levels of myeloperoxidase, TNF-α, IL-6, malondialdehyde, and cleaved caspase-3, a significantly lower GSH level, and histopathological alterations. Moreover, they showed upregulated gene expressions of NF-κB p65 and Bax, downregulated gene expression of Bcl-2, decreased Bcl-2/Bax ratio, and lower protein expression of survivin. OMZ was more effective in protecting the duodenum from indomethacin-induced injuries compared to OM due to improved delivery, higher bioavailability, and better anti-inflammatory, antioxidant, and antiapoptotic effects. OMZ could be a better choice for hypertensive patients with non-steroidal anti-inflammatory drugs-induced duodenitis.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100636&lng=en&tlng=enIndomethacinZeinmersomesOlmesartan medoxomilDuodenitis, Survivin |
| spellingShingle | H.A. Murad T.M. Alqurashi A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in rats Brazilian Journal of Medical and Biological Research Indomethacin Zeinmersomes Olmesartan medoxomil Duodenitis, Survivin |
| title | A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in rats |
| title_full | A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in rats |
| title_fullStr | A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in rats |
| title_full_unstemmed | A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in rats |
| title_short | A novel nano-formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin-induced duodenitis in rats |
| title_sort | novel nano formulation of olmesartan medoxomil with improved delivery and efficacy in the treatment of indomethacin induced duodenitis in rats |
| topic | Indomethacin Zeinmersomes Olmesartan medoxomil Duodenitis, Survivin |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2023000100636&lng=en&tlng=en |
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