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Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid

BACKGROUND: Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect...

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Autores principales: A. Ketuly, Kamal, A. Hadi, A. Hamid, Golbabapour, Shahram, Hajrezaie, Maryam, Hassandarvish, Pouya, Ali, Hapipah Mohd, Majid, Nazia Abdul, Abdulla, Mahmood A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596355/
https://www.ncbi.nlm.nih.gov/pubmed/23516624
http://dx.doi.org/10.1371/journal.pone.0059296
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author A. Ketuly, Kamal
A. Hadi, A. Hamid
Golbabapour, Shahram
Hajrezaie, Maryam
Hassandarvish, Pouya
Ali, Hapipah Mohd
Majid, Nazia Abdul
Abdulla, Mahmood A.
author_facet A. Ketuly, Kamal
A. Hadi, A. Hamid
Golbabapour, Shahram
Hajrezaie, Maryam
Hassandarvish, Pouya
Ali, Hapipah Mohd
Majid, Nazia Abdul
Abdulla, Mahmood A.
author_sort A. Ketuly, Kamal
collection PubMed
description BACKGROUND: Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3′H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats. METHODOLOGY/PRINCIPAL FINDING: Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE(2)) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE(2) as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes. CONCLUSION/SIGNIFICANCE: The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.
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spelling pubmed-35963552013-03-20 Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid A. Ketuly, Kamal A. Hadi, A. Hamid Golbabapour, Shahram Hajrezaie, Maryam Hassandarvish, Pouya Ali, Hapipah Mohd Majid, Nazia Abdul Abdulla, Mahmood A. PLoS One Research Article BACKGROUND: Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3′H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats. METHODOLOGY/PRINCIPAL FINDING: Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE(2)) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE(2) as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes. CONCLUSION/SIGNIFICANCE: The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent. Public Library of Science 2013-03-13 /pmc/articles/PMC3596355/ /pubmed/23516624 http://dx.doi.org/10.1371/journal.pone.0059296 Text en © 2013 A http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
A. Ketuly, Kamal
A. Hadi, A. Hamid
Golbabapour, Shahram
Hajrezaie, Maryam
Hassandarvish, Pouya
Ali, Hapipah Mohd
Majid, Nazia Abdul
Abdulla, Mahmood A.
Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid
title Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid
title_full Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid
title_fullStr Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid
title_full_unstemmed Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid
title_short Acute Toxicity and Gastroprotection Studies with a Newly Synthesized Steroid
title_sort acute toxicity and gastroprotection studies with a newly synthesized steroid
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596355/
https://www.ncbi.nlm.nih.gov/pubmed/23516624
http://dx.doi.org/10.1371/journal.pone.0059296
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