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

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

Differential antibrucella activity of bovine and murine macrophages.

Brucella abortus is an intracellular pathogen affecting macrophages. Macrophages release some antibrucella components such as lysozymes (LZ), reactive oxygen species (ROS) and reactive nitrite intermediates (RNI) which prevent intracellular survival of Brucella. The present study compared the antibrucella activity of bovine and murine macrophages following stimulation with B. abortus lipopolysaccharides. Our results revealed increased production of these antibrucella substances in murine macrophages as compared to bovine macrophages. The differential production of these antibrucella components explained the differential B. abortus killing ability of these species (bovine and mice) that was measured in terms of intramacrophagic survival of Brucellae in murine and bovine macrophages.