scholarly journals Free radical scavengers can modulate the DNA-damaging action of alloxan.

2003 ◽  
Vol 50 (1) ◽  
pp. 205-210 ◽  
Author(s):  
Janusz Blasiak ◽  
Agnieszka Sikora ◽  
Agnieszka Czechowska ◽  
Józef Drzewoski

Alloxan can generate diabetes in experimental animals and its action can be associated with the production of free radicals. It is therefore important to check how different substances often referred to as free radical scavengers may interact with alloxan, especially that some of these substance may show both pro- and antioxidant activities. Using the alkaline comet assay we showed that alloxan at concentrations 0.01-50 microM induced DNA damage in normal human lymphocytes in a dose-dependent manner. Treated cells were able to recover within a 120-min incubation. Vitamins C and E at 10 and 50 microM diminished the extent of DNA damage induced by 50 microM alloxan. Pre-treatment of the lymphocytes with a nitrone spin trap, alpha-(4-pyridil-1-oxide)- N-t-butylnitrone (POBN) or ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), which mimics glutathione peroxides, reduced the alloxan-evoked DNA damage. The cells exposed to alloxan and treated with formamidopyrimidine-DNA glycosylase (Fpg) and 3-methyladenine-DNA glycosylase II (AlkA), enzymes recognizing oxidized and alkylated bases, respectively, displayed greater extent of DNA damage than those not treated with these enzymes. The results confirmed that free radicals are involved in the formation of DNA lesions induced by alloxan. The results also suggest that alloxan can generate oxidized DNA bases with a preference for purines and contribute to their alkylation.

2010 ◽  
Vol 193 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Janusz J. Skolimowski ◽  
Beata Cieślińska ◽  
Marta Żak ◽  
Regina Osiecka ◽  
Alina Błaszczyk

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4353-4353
Author(s):  
Janusz Blasiak ◽  
Jozef Drzewoski ◽  
Tomasz Poplawski ◽  
Agnieszka Czechowska

Abstract Imatinib (STI571) is a 2-phenylaminopyrimidine derivative used mostly in the treatment of chronic myeloid leukaemia. It targets specifically the BCR/ABL oncogenic tyrosine kinase, inhibiting its activity. Using the alkaline comet assay we showed that STI571 at concentrations ranging from 0.05 to 2 μM induced DNA damage in human leukemic K562 cells expressing the BCR/ABL oncogene, whereas it had no effect in normal human lymphocytes. Because the extent of DNA damage observed in the neutral and pH 12.1 versions of the comet assay was much lesser than in the alkaline version, we concluded that the drug induced DNA alkali-labile sites rather than strand breaks. Imatinib did not induce DNA strand breaks in the direct interaction with DNA as examined by the plasmid relaxation assay. K562 cells were unable to repair H2O2-induced DNA damage during a 120-min incubation, if they had been preincubated with STI571, whereas normal lymphocytes did so within 60 min. Pre-treatment of K562 cells with vitamins A, C and E reduced the extent of DNA damage evoked by STI571. Similar results brought experiments with the nitrone spin traps POBN and PBN, suggesting that free radicals may be involved in the formation of DNA lesions induced by STI571 in K562 cells. These cells exposed to imatinib and treated with endonuclease III, formamidopyrimidine-DNA glycosylase and 3-methyladenine-DNA glycosylase II, the enzymes recognizing oxidized and alkylated bases, displayed greater extent of DNA damage than those not treated with these enzymes.


2020 ◽  
Vol 17 (9) ◽  
pp. 1177-1185
Author(s):  
Rafaila Rafique ◽  
Arshia ◽  
Kanwal ◽  
Khalid Mohammed Khan ◽  
Sridevi Chigurupati ◽  
...  

Background: Free radicals are the main cause of numerous diseases. Their overproduction needs to be controlled in order to combat several ailments. The current study deals with the discovery of new free radical scavengers. Methods: Substituted N-hydrazinecarbothioamide indazoles 1-18 were evaluated for DPPH and ABTS radical scavenging activities. Results: All synthetic compounds possess good radical DPPH and ABTS scavenging potential in the ranges of IC50 = 2.11 ± 0.17 - 5.3 ± 0.11 μM and IC50 = 2.31 ± 0.06 - 5.5 ± 0.07 μM, respectively, as compared to standard ascorbic acid having IC50 = 2.02 ± 0.11 μM for DPPH and IC50 = 2.1 ± 0.07 μM for ABTS. Conclusion: These compounds could serve as leads for antioxidant activity that have the ability to control free radical generation and ward off free radical-induced disorders.


2018 ◽  
Vol 16 (11) ◽  
pp. 1890-1902 ◽  
Author(s):  
S. Jeremić ◽  
A. Amić ◽  
M. Stanojević-Pirković ◽  
Z. Marković

In this article, we estimated the scavenger capacity of six selected anthraquinones toward free radicals and their efficacy as inhibitors of P-glycoproteins.


Author(s):  
Raghav Mishra ◽  
Nitin Kumar ◽  
Neetu Sachan

: The field of Free Radical Chemistry has gained considerable interest in the current scenario. The formation of free radicals is attributable to different physiochemical factors, radiation exposure, pathological conditions, environmental contaminants, and as by-products of metabolized drugs. The concentration of free radicals is regulated strongly under normal conditions by physiological antioxidants. Free radicals may cause oxidative damage to proteins, lipids, sugars, and DNA when abundantly produced or when antioxidants are depleted. This imbalance of reduction-oxidation, referred to as oxidative stress, can change the body's physiological conditions and ultimately lead to tissue injury, further contributing to various disease pathologies. A proper balance between free radicals and antioxidants is required for an effective physiological process. The oxidation mechanism is chemically hindered by antioxidants; these are often called free radical scavengers. The application of an external antioxidant source is crucial in addressing the issue of oxidative stress. Plenty of naturally occurring, semi-synthetic, and synthetic antioxidants are used, and the search for an efficient, non-toxic, and safe antioxidant is stepped up over time. As an influential scaffold, thiophene and its derivatives have become a significant source of interest for researchers due to its substantial variety of biological activities. The versatility of thiophene moiety has been identified by an affluent unveiling of its derivatives with anti-inflammatory, antioxidant, anti-cancer, and antimicrobial behaviors. Thiophene activity has been influenced greatly by the nature and orientation of the substitutions. The current study aims at addressing various synthetic compounds with thiophene or condensed thiophene as a fundamental moiety or substituent as radical scavengers.


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