Hydrixyl radical generation by the tetracycline antibiotics with free radical damage to DNA, lipids and carbohydrate in the presence of iron and copper salts

Quinlan, Gregory J.; Gutteridge, John M.C.

doi:10.1016/0891-5849(88)90106-2

Cited by 46 publications

(20 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A significant normalization of the level of the marker enzymes during LUT treatment may be beneficial, as indicated by the protective role of the drug. Increased free radical production stimulates LPO and is the source of the degradation of DNA, lipids and carbohydrates (23). Numerous flavonoid aglycones have been shown to have chain-breaking antioxidant properties and to quench free radicals, thereby exerting protective effects on macromolecules (24).…”

Section: Discussionmentioning

confidence: 99%

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

2016

View full text Add to dashboard Cite

Abstract. Liver cancer is one of the leading causes of cancer-associated mortality worldwide. Due to changes in lifestyle and daily exposure to various chemicals, which may lead to chemical intoxication, liver cancer has become a prominent disease in humans. Chemical-induced carcinogenesis in experimental animals has become a reliable model for the investigation of liver cancer-associated biological alterations that may mimic human hepatic cancer. Liver cancer in BALB/c mice was induced by administering diethylnitrosamine (DN) in drinking water for 6 weeks. Luteolin (LUT) is a flavone that is found in the leaves of the majority of spice-associated plants. In the present study, 20 µg/kg of body weight LUT was administered intraperitoneally every alternate day to treat the DN-induced liver cancer in mice. LUT improved the host system by modifying the levels of α-fetoprotein, enzymatic antioxidants, such as superoxide dismutase and catalase, marker enzymes, such as AST and ALT, and lipid peroxides in the plasma or liver tissue. LUT also reduced the levels of glutathione and the inflammatory cytokines interleukin-2 and interferon-γ in the plasma or liver tissue. These findings augmented the treatment against liver cancer and supported the effective anticancer activity of LUT against DN-induced liver carcinogenesis in mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

2016

View full text Add to dashboard Cite

show abstract

“…With regard to the etiology and prediction of cancer, the technology employed should have wide application to a variety of clinical and laboratory studies in which the status of DNA structure is important. Among such possible applications are studies of the effects of DNA cleaving molecules having selective anti-cancer activity (28,29), DNA damage resulting from radiation (30), antioxidant protection against DNA oxidation (31,32), structural alterations in DNA resulting from hormones (26) and xenobiotics (27), and somatic changes in genes (33).…”

Section: Discussionmentioning

confidence: 99%

Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation

Malins

Polissar

Gunselman

1996

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Wavenumber-absorbance relationships of infrared spectra of DNA analyzed by principal components analysis may be expressed as points in space. Each point represents a highly discriminating measure of DNA structure. Structural modifications of DNA, such as those induced by free radicals, alter vibrational and rotational motion and consequently change the spatial location of the points. Using this technology to analyze breast tumor DNA, we revealed a 94؇ difference in direction between the progression of normal DNA 3 primary tumor DNA and the progression of primary tumor DNA 3 metastatic tumor DNA (P < 0.001). This sharp directional change was accompanied by a substantial increase in the structural diversity of the metastatic tumor DNA (P ‫؍‬ 0.003), which, on the basis of the volume of the core cluster of points, could comprise as many as 11 ؋ 10 9 different phenotypes. This suggests that the heterogeneity and varied physiological properties known to characterize malignant tumor cell populations may at least partially arise from these diverse phenotypes. The evidence suggests that the progression to the metastatic state involves structural modifications in DNA that are markedly different from the modifications associated with the formation of the primary tumor. Overall, the findings of this and earlier studies imply that the observed DNA alterations are a pivotal factor in the etiology of breast cancer and a formidable barrier to overcome in intervention to control the disease. In terms of cancer etiology and prediction, the technology described has potentially wide application to studies in which the structural status of DNA is an important consideration.A significant body of evidence points to the involvement of the hydroxyl radical (⅐OH) in introducing mutagenic structures into DNA of the normal female breast, thus statistically increasing the probability of breast cancer (1-5). In a recent study (5), the transformation of primary breast tumors to the metastatic state was shown to involve a Ͼ2-fold increase in ⅐OH damage in DNA, as indicated by modified nucleotide base models comprising mutagenic 8-hydroxyadenine (6) and the putatively nonmutagenic ring-opened product 4,6-diamino-5-formamidopyrimidine (fapyadenine; refs. 7-11). In addition, plots of the modified nucleotide base model log 10 (fapyadenine͞8-hydroxyadenine) versus the size of metastatic and nonmetastatic breast tumors revealed that the metastatic tumor DNA had significantly greater structural diversity than the nonmetastatic tumor DNA (P ϭ 0.01; ref. 5).Principal components analysis (PCA) of data obtained by Fourier transform-infrared (FT-IR) spectroscopy yielded plots in which individual spectra were represented as points in twoor three-dimensional space. Each point was a highly discriminating representation of an individual DNA structure in that spatially and visually close points had Ͻ3% average spectral difference over the range 1750-700 cm Ϫ1 (5). The core cluster of metastatic tumor DNA points was substantially larger than the core c...

show abstract

“…Among other suggested mechanisms, ROS generation, as indicated by a few reports, may be increased in the presence of certain tetracyclines, e.g., OTC (21,29). However, a role for ROS in the mechanism of OTC action has yet to be clearly established.…”

mentioning

confidence: 99%

Copper/Zinc-Superoxide Dismutase Is Required for Oxytetracycline Resistance of Saccharomyces cerevisiae

et al. 2000

View full text Add to dashboard Cite

Saccharomyces cerevisiae, along with other eukaryotes, is resistant to tetracyclines. We found that deletion of SOD1 (encoding Cu/Zn superoxide dismutase) rendered S. cerevisiae hypersensitive to oxytetracycline (OTC): a sod1⌬ mutant exhibited a >95% reduction in colony-forming ability at an OTC concentration of 20 g ml ؊1 , whereas concentrations of up to 1,000 g ml ؊1 had no effect on the growth of the wild type. OTC resistance was restored in the sod1⌬ mutant by complementation with wild-type SOD1. The effect of OTC appeared to be cytotoxic and was not evident in a ctt1⌬ (cytosolic catalase) mutant or in the presence of tetracycline. SOD1 transcription was not induced by OTC, suggesting that constitutive SOD1 expression is sufficient for wild-type OTC resistance. OTC uptake levels in wild-type and sod1⌬ strains were similar. However, lipid peroxidation and protein oxidation were both enhanced during exposure of the sod1⌬ mutant, but not the wild type, to OTC. We propose that Sod1p protects S. cerevisiae against a mode of OTC action that is dependent on oxidative damage.Reactive oxygen species (ROS) are generated during normal cellular respiratory metabolism, but their damaging effects are generally suppressed by antioxidant defenses. Protective enzymes operating in the budding yeast Saccharomyces cerevisiae are well characterized (30); these include superoxide dismutases (SODs) and catalases, which specifically protect against O 2 ⅐ Ϫ and H 2 O 2 , respectively. S. cerevisiae mutants lacking the principal cellular SOD (Cu/Zn SOD; encoded by SOD1) display certain aerobic growth defects, e.g., reduced growth rate, and methionine and lysine auxotrophies (4). Moreover, sod1⌬ strains are hypersensitive to several types of stress, including oxidative stress (16), metal toxicity (6, 36), prolonged stationary incubation (24), and freeze-thaw stress (28). Such evidence has underscored the central role of ROS in mediating various stresses. However, there is presently no evidence to suggest that antioxidant defenses play a role in the insensitivity of eukaryotes, such as S. cerevisiae, to the action of prokaryotespecific antibiotics.The tetracyclines (e.g., tetracycline, doxycycline, and oxytetracycline [OTC]) are classic broad-spectrum bacteriostatic antibiotics. They are commonly thought to act by inhibiting protein synthesis, through inhibition of binding by aminoacyltRNA to the ribosomal A site (22). Although binding of the tetracyclines to eukaryotic ribosomes occurs in vitro, the in vivo insensitivity of eukaryotes to these antibiotics is usually considered a reflection of the inaccessibility of tetracyclines to the eukaryotic intracellular environment (19); genes conferring OTC resistance to prokaryotes generally encode OTC export proteins (18, 32). The generality of fungal tetracycline resistance is exemplified by the use of OTC in fungiselective growth media (Difco manual, Difco, Detroit, Mich.) and the opportunistic yeast infections that commonly arise following tetracycline administration to humans (22).Inhib...

show abstract

Hydrixyl radical generation by the tetracycline antibiotics with free radical damage to DNA, lipids and carbohydrate in the presence of iron and copper salts

Cited by 46 publications

References 32 publications

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation

Copper/Zinc-Superoxide Dismutase Is Required for Oxytetracycline Resistance of Saccharomyces cerevisiae

Contact Info

Product

Resources

About