Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals
Souraya Domiati,1 Mohammed Mehanna,2,3 Hanan Ragab,4 Hania Nakkash Chmaisse,1 Ahmed El Mallah5 1Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut, Le...
Guardado en:
| Autores principales: | , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2018
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/2ddb7569d8e44abfa6fa830345e19290 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:2ddb7569d8e44abfa6fa830345e19290 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:2ddb7569d8e44abfa6fa830345e192902021-12-02T00:21:56ZInvestigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals1178-7031https://doaj.org/article/2ddb7569d8e44abfa6fa830345e192902018-04-01T00:00:00Zhttps://www.dovepress.com/investigation--of-chronic-efficacy-and-safety-profile-of-two-potential-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Souraya Domiati,1 Mohammed Mehanna,2,3 Hanan Ragab,4 Hania Nakkash Chmaisse,1 Ahmed El Mallah5 1Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 3Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 5Department of Pharmacology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt 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. Keywords: peptic ulcer, hepatic injury, kidney injury, nonsteroidal anti-inflammatory drugs, pyrazole, histologyDomiati SMehanna MRagab HNakkash Chmaisse HEl Mallah ADove Medical PressarticlePeptic ulcerHepatic injurykidney injuryNon-steroidal Anti-inflammatory drugsPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 11, Pp 143-153 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Peptic ulcer Hepatic injury kidney injury Non-steroidal Anti-inflammatory drugs Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
Peptic ulcer Hepatic injury kidney injury Non-steroidal Anti-inflammatory drugs Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Domiati S Mehanna M Ragab H Nakkash Chmaisse H El Mallah A Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals |
| description |
Souraya Domiati,1 Mohammed Mehanna,2,3 Hanan Ragab,4 Hania Nakkash Chmaisse,1 Ahmed El Mallah5 1Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 3Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 5Department of Pharmacology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt 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. Keywords: peptic ulcer, hepatic injury, kidney injury, nonsteroidal anti-inflammatory drugs, pyrazole, histology |
| format |
article |
| author |
Domiati S Mehanna M Ragab H Nakkash Chmaisse H El Mallah A |
| author_facet |
Domiati S Mehanna M Ragab H Nakkash Chmaisse H El Mallah A |
| author_sort |
Domiati S |
| title |
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_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_sort |
investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals |
| publisher |
Dove Medical Press |
| publishDate |
2018 |
| url |
https://doaj.org/article/2ddb7569d8e44abfa6fa830345e19290 |
| work_keys_str_mv |
AT domiatis investigationofchronicefficacyandsafetyprofileoftwopotentialantiinflammatorybipyrazolebasedcompoundsinexperimentalanimals AT mehannam investigationofchronicefficacyandsafetyprofileoftwopotentialantiinflammatorybipyrazolebasedcompoundsinexperimentalanimals AT ragabh investigationofchronicefficacyandsafetyprofileoftwopotentialantiinflammatorybipyrazolebasedcompoundsinexperimentalanimals AT nakkashchmaisseh investigationofchronicefficacyandsafetyprofileoftwopotentialantiinflammatorybipyrazolebasedcompoundsinexperimentalanimals AT elmallaha investigationofchronicefficacyandsafetyprofileoftwopotentialantiinflammatorybipyrazolebasedcompoundsinexperimentalanimals |
| _version_ |
1718403791256027136 |