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Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening

Cardiac tissue engineering describes techniques to constitute three dimensional force-generating engineered tissues. For the implementation of these ...

University Medical Center Hamburg-Eppendorf and DZHK (German Center for Cardiovascular Research)

Tuberculosis (TB) is one of the leading infectious causes of death due to single infectious agent after HIV/AIDS. Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA) and/or their combinations are extensively prescribed to treat TB. Despite several therapeutic implications, these drugs also produce several toxic effects at cellular level. MTT assay and Ames test were adopted in this study for the determination of cytotoxic and mutagenic potential of these anti-TB drugs. Among all tested drugs, cytotoxic potential of RIF was strongest with highly significant decline (p<0.001) in cell numbers at the concentration of 250μg/ml with LC50 at 325μg/ml, while significant decline (p<0.01) in cell count was observed in INH treated group at the concentration 500μg/ml with LC50 at 1000μg/ml. Moreover, combination RIPE demonstrated significant reduction (p<0.01) in cell number at the concentration of 25-500-500-500μg/ml with LC50 at 60-1200-1200-1200μg/ml. It is apparent from the data that almost all drugs represented identical mutagenic pattern i.e., more significant results were achieved in TA100 with metabolic activation (+S9). RIF proved to be highly mutagenic of all tested drugs with significant mutagenicity (p<0.01) at 0.0525μg/plate against TA98 strain with S9. The combination RIPE exhibited highly significant mutagenic activity (p<0.01) at concentration 0.125-3-3-3μg/plate without S9, while addition of S9 resulted in similar activity at lower doses, i.e., 0.0525-1-1-1μg/plate. It was concluded from the data that all anti-TB drugs possess significant cytotoxic and mutagenic potential, especially in combination, making TB patient more vulnerable to cytotoxic and mutagenic effects of anti-TB drugs, which could produce further health complications in TB patients.

In vitro toxic action potential of anti tuberculosis drugs and their combinations.

Excessive use of pesticides poses increased risks to non target species including humans. In the developing countries, lack of proper awareness about the toxic potential of pesticides makes the farmer more vulnerable to pesticide linked toxicities, which could lead to diverse pathological conditions. The toxic potential of a pesticide could be determined by their ability to induce genetic mutations and cytotoxicity. Hence, determination of genetic mutation and cytotoxicity of each pesticide is unavoidable to legislate health and safety appraisal about pesticides. The objective of current investigation was to determine the genotoxic and cytotoxic potential of Endosulfan (EN) and Lambda-cyhalothrin (LC); individually and in combination. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay was utilized to determine cytotoxicity, while two mutant histidine dependent Salmonella strains (TA98, TA100) were used to determine the mutagenicity of EN and LC. Moreover, mutagenicity assay was conducted with and without S9 to evaluate the effects of metabolic activation on mutagenicity. Even though a dose dependent increase in the number of revertant colonies was detected with EN against both bacterial strains, a highly significant (p<0.05) increase in the mutagenicity was detected in TA98 with S9. In comparison, data obtained from LC revealed less mutagenic potential than EN. Surprisingly, the non-mutagenic individual-concentrations of EN and LC showed dose dependent mutagenicity when combined. Combination of EN and LC synergistically induced mutagenicity both in TA98 and TA100. MTT assay spotlighted comparable dose dependent cytotoxicity effects of both pesticides. Interestingly, the combination of EN and LC produced increased reversion and cytotoxicity at lower doses as compared to each pesticide, concluding that pesticide exposure even at sub-lethal doses can produce cytotoxicity and genetic mutations, which could lead to carcinogenicity.

Umber Saleem

Department of Experimental Pharmacology and Toxicology,
Cardiovascular Research Center,
Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center

University Medical Center Hamburg-Eppendorf and DZHK (German Center for Cardiovascular Research)

Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening

Umber Saleem

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Experimental Pharmacology and Toxicology,Cardiovascular Research Center,Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center

University Medical Center Hamburg-Eppendorf and DZHK (German Center for Cardiovascular Research)

Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening

Department of Experimental Pharmacology and Toxicology,
Cardiovascular Research Center,
Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center