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Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals

PURPOSE: Although nonsteroidal anti-inflammatory drugs are widely used to treat a variety of disorders, their administration is associated with gastrointestinal side effects, acute kidney injury and liver enzymes’ elevation. Accordingly, researchers are encouraged to create novel agents with better...

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Autores principales: Domiati, Souraya, Mehanna, Mohammed, Ragab, Hanan, Nakkash Chmaisse, Hania, El Mallah, Ahmed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892962/
https://www.ncbi.nlm.nih.gov/pubmed/29662323
http://dx.doi.org/10.2147/JIR.S157955
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author Domiati, Souraya
Mehanna, Mohammed
Ragab, Hanan
Nakkash Chmaisse, Hania
El Mallah, Ahmed
author_facet Domiati, Souraya
Mehanna, Mohammed
Ragab, Hanan
Nakkash Chmaisse, Hania
El Mallah, Ahmed
author_sort Domiati, Souraya
collection PubMed
description PURPOSE: Although nonsteroidal anti-inflammatory drugs are widely used to treat a variety of disorders, their administration is associated with gastrointestinal side effects, acute kidney injury and liver enzymes’ elevation. Accordingly, researchers are encouraged to create novel agents with better safety profile. The aim of the current study was to evaluate the chronic efficacy and safety profile of two compounds previously proven to have acceptable acute anti-inflammatory and analgesic activities. MATERIALS AND METHODS: Doses were determined through formalin-induced mice paw edema-based dose–response curves. Granuloma weight was used to assess the chronic effect of the investigated compounds as compared to the vehicle and diclofenac representing the positive and the negative controls, respectively. Mice kidneys, livers and stomachs were histologically examined. Moreover, troponin I, alanine aminotransferase, aspartate aminotransferase, serum creatinine and blood urea nitrogen levels were measured. RESULTS: The results highlight that the granulomas and exudates developed in mice after 7 days of treatment, with compound I and compound II were significantly lower than that of the negative control group. Moreover, compound I showed significantly better anti-inflammatory effect than diclofenac. Troponin level was undetected in all groups. Histopathological examination of the stomach revealed normal mucosa for both tested compounds and controls. Likewise, kidneys showed neither significant histologic alteration nor biomarkers increase as compared to the control over both 7- and 30-day treatment periods. Mice that received the tested compounds or diclofenac exhibited transient liver damage specifically; congestion, vacuolization, necrosis and inflammation after 7 days of treatment which decreased significantly after 30 days of treatment as emphasized by the Suzuki score and biomarker levels. CONCLUSION: Since the tested compounds, specifically compound I, presented a satisfactory chronic safety profile as well as anti-inflammatory effect, it is worth conducting further molecular pharmacological, toxicological and bioavailability studies to elucidate the efficacy of these potential anti-inflammatory bipyrazole compounds.
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spelling pubmed-58929622018-04-16 Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals Domiati, Souraya Mehanna, Mohammed Ragab, Hanan Nakkash Chmaisse, Hania El Mallah, Ahmed J Inflamm Res Original Research PURPOSE: Although nonsteroidal anti-inflammatory drugs are widely used to treat a variety of disorders, their administration is associated with gastrointestinal side effects, acute kidney injury and liver enzymes’ elevation. Accordingly, researchers are encouraged to create novel agents with better safety profile. The aim of the current study was to evaluate the chronic efficacy and safety profile of two compounds previously proven to have acceptable acute anti-inflammatory and analgesic activities. MATERIALS AND METHODS: Doses were determined through formalin-induced mice paw edema-based dose–response curves. Granuloma weight was used to assess the chronic effect of the investigated compounds as compared to the vehicle and diclofenac representing the positive and the negative controls, respectively. Mice kidneys, livers and stomachs were histologically examined. Moreover, troponin I, alanine aminotransferase, aspartate aminotransferase, serum creatinine and blood urea nitrogen levels were measured. RESULTS: The results highlight that the granulomas and exudates developed in mice after 7 days of treatment, with compound I and compound II were significantly lower than that of the negative control group. Moreover, compound I showed significantly better anti-inflammatory effect than diclofenac. Troponin level was undetected in all groups. Histopathological examination of the stomach revealed normal mucosa for both tested compounds and controls. Likewise, kidneys showed neither significant histologic alteration nor biomarkers increase as compared to the control over both 7- and 30-day treatment periods. Mice that received the tested compounds or diclofenac exhibited transient liver damage specifically; congestion, vacuolization, necrosis and inflammation after 7 days of treatment which decreased significantly after 30 days of treatment as emphasized by the Suzuki score and biomarker levels. CONCLUSION: Since the tested compounds, specifically compound I, presented a satisfactory chronic safety profile as well as anti-inflammatory effect, it is worth conducting further molecular pharmacological, toxicological and bioavailability studies to elucidate the efficacy of these potential anti-inflammatory bipyrazole compounds. Dove Medical Press 2018-04-03 /pmc/articles/PMC5892962/ /pubmed/29662323 http://dx.doi.org/10.2147/JIR.S157955 Text en © 2018 Domiati et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Domiati, Souraya
Mehanna, Mohammed
Ragab, Hanan
Nakkash Chmaisse, Hania
El Mallah, Ahmed
Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals
title Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals
title_full Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals
title_fullStr Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals
title_full_unstemmed Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals
title_short Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals
title_sort investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892962/
https://www.ncbi.nlm.nih.gov/pubmed/29662323
http://dx.doi.org/10.2147/JIR.S157955
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