Augmented cytotoxic, mutagenic and genotoxic response triggered by carvedilol and celecoxib combinations

Ali Attiq, Muhammad Ashraf, Juriyati Jalil, Aqeel Javeed, Aftab Ahmad Anjum, Asad Ullah, Muhammad Umair, Sarwat Ali

Research output: Contribution to journalArticle

Abstract

It is understood that drugs regardless of their order of administration can exhibit drug interactions. Established on the fact that treatment of hypertension may last for decades and prolong usage of multiple drug regimen may induce substantial pathophysiological changes. Hence, This study was designed to evaluate the possible synergistic toxic effects of anti-hypertensive (carvedilol), and anti-inflammatory drug (celecoxib) alone and in combinations. Well-established MTT assay, Single Cell Gel Electrophoresis (SCGE) and Ames assay were employed to evaluate the toxicity at cellular level. Results from MTT assay on Vero cell line revealed that drug combinations have more pronounced anti-proliferative activity with combine IC50 value of 13.7:47.8 µg/mL. Likewise, exposure of peripheral blood mononuclear cells with drug combinations revealed significant (P<0.05) DNA damage (Class 3) in a dose dependent manner at concentrations = 0.78: 2.34 µg/mL. However, carvedilol and celecoxib were non mutagenic against either mutant strain (TA 100 and TA 98) and combinations have also shown mild to moderate mutagenic potential. Nevertheless, upon addition of metabolic activation enzyme, concentration <12.5:37.5 µg/plate exhibited significant (P<0.05) mutagenicity against both tester strains. In conclusion, this study provides additional genotoxicity and mutagenicity data that could be used in considering options for formulating regimens with reduced mutagenic potential.

Original languageEnglish
Article numbere17292
JournalBrazilian Journal of Pharmaceutical Sciences
Volume54
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Celecoxib
Drug Combinations
Pharmaceutical Preparations
Vero Cells
Comet Assay
Poisons
Drug Interactions
Antihypertensive Agents
Inhibitory Concentration 50
DNA Damage
Blood Cells
Anti-Inflammatory Agents
Hypertension
Cell Line
Enzymes
carvedilol

Keywords

  • Carvedilol
  • Celecoxib
  • Cytotoxicity
  • Genotoxicity
  • Mutagenicity

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Augmented cytotoxic, mutagenic and genotoxic response triggered by carvedilol and celecoxib combinations. / Attiq, Ali; Ashraf, Muhammad; Jalil, Juriyati; Javeed, Aqeel; Anjum, Aftab Ahmad; Ullah, Asad; Umair, Muhammad; Ali, Sarwat.

In: Brazilian Journal of Pharmaceutical Sciences, Vol. 54, No. 1, e17292, 01.01.2018.

Research output: Contribution to journalArticle

Attiq, Ali ; Ashraf, Muhammad ; Jalil, Juriyati ; Javeed, Aqeel ; Anjum, Aftab Ahmad ; Ullah, Asad ; Umair, Muhammad ; Ali, Sarwat. / Augmented cytotoxic, mutagenic and genotoxic response triggered by carvedilol and celecoxib combinations. In: Brazilian Journal of Pharmaceutical Sciences. 2018 ; Vol. 54, No. 1.
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