Kanser tedavisinde antikanser etkiyi artırmak ve sitotoksisiteyi azaltmak amacıyla kemoterapötik ... more Kanser tedavisinde antikanser etkiyi artırmak ve sitotoksisiteyi azaltmak amacıyla kemoterapötik ilaçlar ile birlikte çeşitli bitkisel kökenli fenolik bileşiklerin kullanımı hedeflenmektedir. Bir fenolik bileşik olan Piknogenol ® (PYC), birçok çalışmanın konusu olmaktadır. PYC'nin sisplatin ile etkileşme mekanizması tam olarak aydınlatılamadığı için insan serviks kanser hücrelerinde (HeLa) sisplatin sitotoksisitesi üzerine PYC'nin etkilerini belirlemeyi ve PYC'nin sitotoksik olmayan dozlarında PYC'nin genotoksisitesini değerlendirilmeyi hedefledik. Gereç ve Yöntemler: HeLa hücrelerinde, 24 ve 48 saatlik maruziyetlerde, PYC varlığında ve yokluğunda sisplatinin sitotoksisitesi 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür (MTT) yöntemi ile ölçüldü. Oksidatif DNA hasarına karşı PYC'nin etkisi Comet yöntemi ile değerlendirildi. Bulgular: Sisplatinin IC 50 değeri 24 saat ve 48 saat için sırasıyla 22,4 µM ve 12,3 µM idi. PYC'nin IC 50 değerleri 24 saat ve 48 saat için sırasıyla 261 µM ve 213 µM idi. Yirmi dört saatlik maruziyet için, PYC'nin, seçilen konsantrasyonlarda (15,6-500 µM) sisplatinin IC 50 değerini önemli ölçüde azalttı. Kırk sekiz saat maruziyet için, PYC sisplatinin sitotoksisitesini 15,6-125 µM arasındaki konsantrasyonlarda değiştirmedi, ancak 250 µM ve 500 µM konsantrasyonlarda önemli ölçüde azalttı. PYC tek başına 10 µM ve 25 µM konsantrasyonlarında DNA hasarına neden olmadı, ancak daha yüksek konsantrasyonlarında (50-100 µM) DNA hasarını önemli ölçüde indükledi. Ayrıca, çalışılan tüm konsantrasyonlarında (10-100 µM) 50 µM H 2 O 2 tarafından indüklenen DNA hasarını önemli ölçüde azalttı. Objectives: In the treatment of cancer, it is intended to increase the anticancer effect and decrease cytotoxicity using various plant-derived phenolic compounds with chemotherapeutic drugs. Pycnogenol ® (PYC), a phenolic compound, has been the subject of many studies. Since the mechanisms of the interactions of PYC with cisplatin need to be clarified, we aimed to determine the effects of PYC on cisplatin cytotoxicity in human cervix cancer cells (HeLa) and to evaluate the genotoxicity of PYC. Materials and Methods: The cytotoxicity of cisplatin and PYC was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HeLa cells for 24 h and 48 h. The effect of PYC against oxidative DNA damage was evaluated using the comet assay. Results: The IC 50 values of cisplatin were 22.4 µM and 12.3 µM for 24 h and 48 h, respectively. The IC 50 values of PYC were 261 µM and 213 µM for 24 h and 48 h, respectively. For 24 h exposure, PYC significantly reduced the IC 50 value of cisplatin at the selected concentrations (15.6-500 µM). For 48 h exposure, PYC did not change the cytotoxicity of cisplatin at concentrations between 15.6 and 125 µM, but significantly reduced it at concentrations of 250 µM and 500 µM. PYC alone did not induce DNA damage at concentrations of 10 µM or 25 µM; however, it significantly induced DNA damage at higher concentrations (50-100 µM). It also significantly reduced H 2 O 2-induced DNA damage at all concentrations studied (10-100 µM). Conclusion: Our results suggest that PYC may increase the cisplatin cytotoxicity in HeLa cells at nongenotoxic doses. The results might contribute to the anticancer effect of cisplatin with PYC in cervical carcinoma, but in order to confirm this result further in vitro studies with cancer cell lines and in vivo studies are needed.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1998
The flavonoids, silymarin, myricetin, quercitin, kaempferol, rutin and kaempferol-3-rutinoside ha... more The flavonoids, silymarin, myricetin, quercitin, kaempferol, rutin and kaempferol-3-rutinoside have been examined in combination with the food mutagens, 3-amino-1-methyl-5H-pyrido (4,3-b)indole (Trp-P-2) and 2-amino-3-methylimidazo-(4,5-f) quinoline (IQ), in the Comet assay in human lymphocytes from donor A and human sperm from donor B. These compounds alone have been shown to produce positive responses in the Comet assay, as have the food mutagens. However, in combination with the food mutagens, the flavonoids produced antigenotoxic effects since DNA damage was reduced in the Comet assay in lymphocytes and sperm. The assays were performed in the absence of metabolic activation, since when quercetin and kaempferol were examined in blood with metabolic activation, there was little or no difference in response to that obtained in its absence. In the blood, there was an exacerbation or synergy of response at the lowest doses of the flavonoids. In the sperm, with silymarin, myricetin and quercitin, antigenotoxic effects only were observed, but with kaempferol, in general, there were no protective effects. The food mutagen, 2-amino-1-methyl-6-phenylimadazo (4,5-b)pyridine (PhIP), was also examined in addition to Trp-P-2 and IQ in combination with silymarin and myricetin in donors A and C in human lymphocytes only. Similar exacerbation of effects were found at low doses of these flavonoids with antigenotoxic effects at high doses. This was confirmed in the Ames test. There were slightly different profiles in lymphocytes and sperm, but antigenotoxic effects were observed over a similar dose range. This would suggest that effects occur in somatic and germ cells on a one-to-one ratio. These results have implications for man in terms of risk assessment and in the modulation of isolated food constituents.
Reactive oxygen species are believed to be involved in the development of sepsis. Plant-derived p... more Reactive oxygen species are believed to be involved in the development of sepsis. Plant-derived phenolic compounds are thought to be possible therapeutic agents against sepsis because of their antioxidant properties. Rosmarinic acid (RA) is a phenolic compound commonly found in various plants, which has many biological activities including antioxidant activity. The aim of this study was to investigate the effects of RA on sepsis-induced DNA damage in the lymphocytes and liver and kidney cells of Wistar albino rats by alkaline comet assay with and without formamidopyrimidine DNA glycosylase protein. The oxidative stress parameters such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and total glutathione (GSH) and malondialdehyde (MDA) levels in the liver and kidney tissues and an inflammatory cytokine, tumor necrosis factor α (TNF-α) level in plasma were also evaluated. It is found that DNA damage in the lymphocytes, livers, and kidneys of the RA-treated...
The present study was carried out to investigate the modulating effects of the two flavonoids que... more The present study was carried out to investigate the modulating effects of the two flavonoids quercetin and rutin on the mutagenic anticancer drug mitomycin C by single cell gel electrophoresis (Comet assay) in human lymphocytes. Lymphocytes were incubated with different concentrations of quercetin and rutin, with or without mitomycin C, and DNA damage was evaluated. Concentrations of 0.03, 0.15, 0.3, 0.6, 1.5 and 3mM quercetin significantly reduced the DNA strand breakage induced by mitomycin C (P<0.001) but the highest concentration of 6mM quercetin did not show a protective effect. The frequency of damaged cells induced by mitomycin C was not changed at 0.02 mM, and also at the highest concentrations of 1.64 and 3.28 mM rutin. However, at concentrations of 0.08, 0.16, 0.33 and 0.82 mM rutin cells were protected from DNA damage. Thus, in human lymphocytes quercetin and rutin displayed protective effects on DNA damage induced by mitomycin C, in a concentration-dependent manner.
Three new phenylpropanoid glycosides, phlinosides A, B and C were isolated from a methanolic extr... more Three new phenylpropanoid glycosides, phlinosides A, B and C were isolated from a methanolic extract of the aerial parts of Phlomis linearis. On the basis of chemical and spectral evidence their structures were determined
Two new phenethyl alcohol glycosides, darendoside A and B (= deacyl martynoside) were isolated fr... more Two new phenethyl alcohol glycosides, darendoside A and B (= deacyl martynoside) were isolated from the methanolic extract of the aerial parts of Scutellaria orientalis subsp. pinnatifida, along with four known glycosides, syringin, martynoside, leucosceptoside A and verbascoside. On the basis of chemical and spectral evidence the structures of darendoside A and B were determined as beta-(4-hydroxyphenyl)ethyl O-beta-D-apiofuranosyl-(1-->2)-O-beta-D-glucopyranoside and beta-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-rhamnopyranosyl-(1-->3)-O-beta-D-glucopyranoside (= deacyl martynoside), respectively.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2005
The leafy parts of thyme and its essential oil have been used in foods for its flavour, aroma and... more The leafy parts of thyme and its essential oil have been used in foods for its flavour, aroma and preservation for many years. In the present study the genotoxic potential of major compounds of thyme oil, i.e. thymol, carvacrol, and ␥-terpinene and of the methanolic extracts of thyme, were investigated in human lymphocytes by single-cell gel electrophoresis. Also, the effects of these substances on the induction of DNA damage by 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and mitomycin C (MMC) were evaluated. No increase in DNA strand breakage was observed at thymol and ␥-terpinene concentrations below 0.1 mM, but at the higher concentration of 0.2 mM significant increases in DNA damage were seen. Thymol and ␥-terpinene significantly reduced the DNA strand breakage induced by IQ and MMC at the lower concentrations studied. Carvacrol, which is an isomer of thymol, seemed to protect lymphocytes from the genotoxic effects of IQ and MMC at non-toxic concentrations below 0.05 mM, but at the higher concentration of 0.1 mM carvacrol itself induced DNA damage. Also the constituents of the n-hexane and ethyl acetate fractions prepared from the concentrated aqueous methanolic extracts of Thymus spicata protected lymphocytes against IQ-and MMC-induced DNA damage in a concentration-dependent manner.
The present study was carried out to investigate the modulating effects of thyme and its major co... more The present study was carried out to investigate the modulating effects of thyme and its major components against the oxidative DNA damage induced by H 2 O 2. The human lymphocytes with thymol, carvacrol, and γ-terpinene incubated with or without 0.1 mM H 2 O 2 for 30 min at 37°C and the DNA damage were evaluated by singe cell gel electropheresis (comet assay). Concentrations above 0.1 mM thymol and γ-terpinene and 0.05 mM carvacrol significantly induced DNA damage in human lymphocytes, but at the smaller concentrations no additional DNA strand breakage has been observed. At the all concentrations studied, γ-terpinene did not show any protective effect against H 2 O 2 induced oxidative DNA damage, but the phenolic compounds thymol and carvacrol at concentrations below 0.2 and 0.1 mM, respectively, significantly reduced the oxidative DNA damage (p < 0.001). The n-hexane and ethyl acetate fractions prepared from the methanolic extracts of Thymus spicata also were found to inhibit DNA damage.
Sepsis, often initiated by an infection, is a state of disrupted inflammatory homeostasis. There ... more Sepsis, often initiated by an infection, is a state of disrupted inflammatory homeostasis. There is increasing evidence that oxidative stress has an important role in the development of sepsis-induced multiorgan failure. Resveratrol (RV) is a polyphenolic compound found in the skin of red fruits, such as mulberries and red grapes, and in peanuts. RV has been reported to have an antioxidant, antiproliferative, and anti-inflammatory properties in various models. It has also been found to inhibit the proliferation of a variety of human cancer cell lines, including breast, prostate, colon, pancreatic, and thyroid. This study has been undertaken to assess the role of RV on the sepsis-induced oxidative DNA damage in the lymphocytes of Wistar albino rats by the standard and formamidopyrimidine DNA glycosylase (Fpg)-modified comet assays. The parameters of tail length, tail intensity, and tail moment were evaluated for the determination of DNA damage. According to the study, the DNA damage ...
The leafy parts of thyme and its essential oil have been used in foods for the flavour, aroma and... more The leafy parts of thyme and its essential oil have been used in foods for the flavour, aroma and preservation and also in folk medicines. In the present study the genotoxicity of thymol and carvacrol was examined using comet assay. In V79 Chinese hamster lung fibroblast cells treated with 1, 5, 25 microM thymol and carvacrol, only 25 microM thymol caused some clastogenic DNA damage. For detection of oxidative DNA damage, the comet assay with formamido pyrimidine glycosylase (Fpg) protein was used: When V79 cells were treated with 1, 5, 25 microM thymol and carvacrol and post-treated with Fpg enzyme, no significant increase of Fpg-sensitive sites was observed at all concentrations studied. Reactive oxygen species (ROS) generation decreased slightly in the presence of thymol (1-100 microM) and carvacrol (5 microM) between 1 and 4h, yet increased at the highest 100 microM concentration of carvacrol after 24h. Thymol and carvacrol displayed a concentration dependent antioxidant capacity, whilst gamma-terpinene which lacks a phenolic group did not show any antioxidant capacity in the trolox equivalent antioxidant capacity (TEAC) assay. The results of this study indicate a lack of clastogenic activity for thymol and carvacrol at biologically relevant concentrations, and a moderate antioxidant activity in vitro.
Two new phenylpropanoid glycosides, phlinosid~ D and E were isolated from the methanolic extract ... more Two new phenylpropanoid glycosides, phlinosid~ D and E were isolated from the methanolic extract of the aerial parts of Phlomis line&s, along with the known iridoid glucosides, lamiide, ipolamiide and auroside (= 5hydroxy-8epiloganin). On the basis of chemical and spectral evidence the structures of phlinosides D and E were determined as 3
The present study was carried out to investigate the modulating effects of thyme and its major co... more The present study was carried out to investigate the modulating effects of thyme and its major components against the oxidative DNA damage induced by H(2)O(2). The human lymphocytes with thymol, carvacrol, and gamma-terpinene incubated with or without 0.1 mM H(2)O(2) for 30 min at 37 degrees C and the DNA damage were evaluated by singe cell gel electropheresis (comet assay). Concentrations above 0.1 mM thymol and gamma-terpinene and 0.05 mM carvacrol significantly induced DNA damage in human lymphocytes, but at the smaller concentrations no additional DNA strand breakage has been observed. At the all concentrations studied, gamma-terpinene did not show any protective effect against H(2)O(2) induced oxidative DNA damage, but the phenolic compounds thymol and carvacrol at concentrations below 0.2 and 0.1 mM, respectively, significantly reduced the oxidative DNA damage (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The n-hexane and ethyl acetate fractions prepared from the methanolic extracts of Thymus spicata also were found to inhibit DNA damage.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2005
The leafy parts of thyme and its essential oil have been used in foods for its flavour, aroma and... more The leafy parts of thyme and its essential oil have been used in foods for its flavour, aroma and preservation for many years. In the present study the genotoxic potential of major compounds of thyme oil, i.e. thymol, carvacrol, and ␥-terpinene and of the methanolic extracts of thyme, were investigated in human lymphocytes by single-cell gel electrophoresis. Also, the effects of these substances on the induction of DNA damage by 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and mitomycin C (MMC) were evaluated. No increase in DNA strand breakage was observed at thymol and ␥-terpinene concentrations below 0.1 mM, but at the higher concentration of 0.2 mM significant increases in DNA damage were seen. Thymol and ␥-terpinene significantly reduced the DNA strand breakage induced by IQ and MMC at the lower concentrations studied. Carvacrol, which is an isomer of thymol, seemed to protect lymphocytes from the genotoxic effects of IQ and MMC at non-toxic concentrations below 0.05 mM, but at the higher concentration of 0.1 mM carvacrol itself induced DNA damage. Also the constituents of the n-hexane and ethyl acetate fractions prepared from the concentrated aqueous methanolic extracts of Thymus spicata protected lymphocytes against IQ-and MMC-induced DNA damage in a concentration-dependent manner.
Two new phenethyl alcohol glycosides, darendoside A and B (= deacyl martynoside) were isolated fr... more Two new phenethyl alcohol glycosides, darendoside A and B (= deacyl martynoside) were isolated from the methanolic extract of the aerial parts of Scutellaria orientalis subsp. pinnatifida, along with four known glycosides, syringin, martynoside, leucosceptoside A and verbascoside. On the basis of chemical and spectral evidence the structures of darendoside A and B were determined as beta-(4-hydroxyphenyl)ethyl O-beta-D-apiofuranosyl-(1--&gt;2)-O-beta-D-glucopyranoside and beta-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-rhamnopyranosyl-(1--&gt;3)-O-beta-D-glucopyranoside (= deacyl martynoside), respectively.
The present study was carried out to investigate the modulating effects of the two flavonoids que... more The present study was carried out to investigate the modulating effects of the two flavonoids quercetin and rutin on the mutagenic anticancer drug mitomycin C by single cell gel electrophoresis (Comet assay) in human lymphocytes. Lymphocytes were incubated with different concentrations of quercetin and rutin, with or without mitomycin C, and DNA damage was evaluated. Concentrations of 0.03, 0.15, 0.3, 0.6, 1.5 and 3mM quercetin significantly reduced the DNA strand breakage induced by mitomycin C (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) but the highest concentration of 6mM quercetin did not show a protective effect. The frequency of damaged cells induced by mitomycin C was not changed at 0.02 mM, and also at the highest concentrations of 1.64 and 3.28 mM rutin. However, at concentrations of 0.08, 0.16, 0.33 and 0.82 mM rutin cells were protected from DNA damage. Thus, in human lymphocytes quercetin and rutin displayed protective effects on DNA damage induced by mitomycin C, in a concentration-dependent manner.
Kanser tedavisinde antikanser etkiyi artırmak ve sitotoksisiteyi azaltmak amacıyla kemoterapötik ... more Kanser tedavisinde antikanser etkiyi artırmak ve sitotoksisiteyi azaltmak amacıyla kemoterapötik ilaçlar ile birlikte çeşitli bitkisel kökenli fenolik bileşiklerin kullanımı hedeflenmektedir. Bir fenolik bileşik olan Piknogenol ® (PYC), birçok çalışmanın konusu olmaktadır. PYC'nin sisplatin ile etkileşme mekanizması tam olarak aydınlatılamadığı için insan serviks kanser hücrelerinde (HeLa) sisplatin sitotoksisitesi üzerine PYC'nin etkilerini belirlemeyi ve PYC'nin sitotoksik olmayan dozlarında PYC'nin genotoksisitesini değerlendirilmeyi hedefledik. Gereç ve Yöntemler: HeLa hücrelerinde, 24 ve 48 saatlik maruziyetlerde, PYC varlığında ve yokluğunda sisplatinin sitotoksisitesi 3-(4,5-dimetiltiyazol-2-il)-2,5-difeniltetrazolyum bromür (MTT) yöntemi ile ölçüldü. Oksidatif DNA hasarına karşı PYC'nin etkisi Comet yöntemi ile değerlendirildi. Bulgular: Sisplatinin IC 50 değeri 24 saat ve 48 saat için sırasıyla 22,4 µM ve 12,3 µM idi. PYC'nin IC 50 değerleri 24 saat ve 48 saat için sırasıyla 261 µM ve 213 µM idi. Yirmi dört saatlik maruziyet için, PYC'nin, seçilen konsantrasyonlarda (15,6-500 µM) sisplatinin IC 50 değerini önemli ölçüde azalttı. Kırk sekiz saat maruziyet için, PYC sisplatinin sitotoksisitesini 15,6-125 µM arasındaki konsantrasyonlarda değiştirmedi, ancak 250 µM ve 500 µM konsantrasyonlarda önemli ölçüde azalttı. PYC tek başına 10 µM ve 25 µM konsantrasyonlarında DNA hasarına neden olmadı, ancak daha yüksek konsantrasyonlarında (50-100 µM) DNA hasarını önemli ölçüde indükledi. Ayrıca, çalışılan tüm konsantrasyonlarında (10-100 µM) 50 µM H 2 O 2 tarafından indüklenen DNA hasarını önemli ölçüde azalttı. Objectives: In the treatment of cancer, it is intended to increase the anticancer effect and decrease cytotoxicity using various plant-derived phenolic compounds with chemotherapeutic drugs. Pycnogenol ® (PYC), a phenolic compound, has been the subject of many studies. Since the mechanisms of the interactions of PYC with cisplatin need to be clarified, we aimed to determine the effects of PYC on cisplatin cytotoxicity in human cervix cancer cells (HeLa) and to evaluate the genotoxicity of PYC. Materials and Methods: The cytotoxicity of cisplatin and PYC was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HeLa cells for 24 h and 48 h. The effect of PYC against oxidative DNA damage was evaluated using the comet assay. Results: The IC 50 values of cisplatin were 22.4 µM and 12.3 µM for 24 h and 48 h, respectively. The IC 50 values of PYC were 261 µM and 213 µM for 24 h and 48 h, respectively. For 24 h exposure, PYC significantly reduced the IC 50 value of cisplatin at the selected concentrations (15.6-500 µM). For 48 h exposure, PYC did not change the cytotoxicity of cisplatin at concentrations between 15.6 and 125 µM, but significantly reduced it at concentrations of 250 µM and 500 µM. PYC alone did not induce DNA damage at concentrations of 10 µM or 25 µM; however, it significantly induced DNA damage at higher concentrations (50-100 µM). It also significantly reduced H 2 O 2-induced DNA damage at all concentrations studied (10-100 µM). Conclusion: Our results suggest that PYC may increase the cisplatin cytotoxicity in HeLa cells at nongenotoxic doses. The results might contribute to the anticancer effect of cisplatin with PYC in cervical carcinoma, but in order to confirm this result further in vitro studies with cancer cell lines and in vivo studies are needed.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1998
The flavonoids, silymarin, myricetin, quercitin, kaempferol, rutin and kaempferol-3-rutinoside ha... more The flavonoids, silymarin, myricetin, quercitin, kaempferol, rutin and kaempferol-3-rutinoside have been examined in combination with the food mutagens, 3-amino-1-methyl-5H-pyrido (4,3-b)indole (Trp-P-2) and 2-amino-3-methylimidazo-(4,5-f) quinoline (IQ), in the Comet assay in human lymphocytes from donor A and human sperm from donor B. These compounds alone have been shown to produce positive responses in the Comet assay, as have the food mutagens. However, in combination with the food mutagens, the flavonoids produced antigenotoxic effects since DNA damage was reduced in the Comet assay in lymphocytes and sperm. The assays were performed in the absence of metabolic activation, since when quercetin and kaempferol were examined in blood with metabolic activation, there was little or no difference in response to that obtained in its absence. In the blood, there was an exacerbation or synergy of response at the lowest doses of the flavonoids. In the sperm, with silymarin, myricetin and quercitin, antigenotoxic effects only were observed, but with kaempferol, in general, there were no protective effects. The food mutagen, 2-amino-1-methyl-6-phenylimadazo (4,5-b)pyridine (PhIP), was also examined in addition to Trp-P-2 and IQ in combination with silymarin and myricetin in donors A and C in human lymphocytes only. Similar exacerbation of effects were found at low doses of these flavonoids with antigenotoxic effects at high doses. This was confirmed in the Ames test. There were slightly different profiles in lymphocytes and sperm, but antigenotoxic effects were observed over a similar dose range. This would suggest that effects occur in somatic and germ cells on a one-to-one ratio. These results have implications for man in terms of risk assessment and in the modulation of isolated food constituents.
Reactive oxygen species are believed to be involved in the development of sepsis. Plant-derived p... more Reactive oxygen species are believed to be involved in the development of sepsis. Plant-derived phenolic compounds are thought to be possible therapeutic agents against sepsis because of their antioxidant properties. Rosmarinic acid (RA) is a phenolic compound commonly found in various plants, which has many biological activities including antioxidant activity. The aim of this study was to investigate the effects of RA on sepsis-induced DNA damage in the lymphocytes and liver and kidney cells of Wistar albino rats by alkaline comet assay with and without formamidopyrimidine DNA glycosylase protein. The oxidative stress parameters such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and total glutathione (GSH) and malondialdehyde (MDA) levels in the liver and kidney tissues and an inflammatory cytokine, tumor necrosis factor α (TNF-α) level in plasma were also evaluated. It is found that DNA damage in the lymphocytes, livers, and kidneys of the RA-treated...
The present study was carried out to investigate the modulating effects of the two flavonoids que... more The present study was carried out to investigate the modulating effects of the two flavonoids quercetin and rutin on the mutagenic anticancer drug mitomycin C by single cell gel electrophoresis (Comet assay) in human lymphocytes. Lymphocytes were incubated with different concentrations of quercetin and rutin, with or without mitomycin C, and DNA damage was evaluated. Concentrations of 0.03, 0.15, 0.3, 0.6, 1.5 and 3mM quercetin significantly reduced the DNA strand breakage induced by mitomycin C (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) but the highest concentration of 6mM quercetin did not show a protective effect. The frequency of damaged cells induced by mitomycin C was not changed at 0.02 mM, and also at the highest concentrations of 1.64 and 3.28 mM rutin. However, at concentrations of 0.08, 0.16, 0.33 and 0.82 mM rutin cells were protected from DNA damage. Thus, in human lymphocytes quercetin and rutin displayed protective effects on DNA damage induced by mitomycin C, in a concentration-dependent manner.
Three new phenylpropanoid glycosides, phlinosides A, B and C were isolated from a methanolic extr... more Three new phenylpropanoid glycosides, phlinosides A, B and C were isolated from a methanolic extract of the aerial parts of Phlomis linearis. On the basis of chemical and spectral evidence their structures were determined
Two new phenethyl alcohol glycosides, darendoside A and B (= deacyl martynoside) were isolated fr... more Two new phenethyl alcohol glycosides, darendoside A and B (= deacyl martynoside) were isolated from the methanolic extract of the aerial parts of Scutellaria orientalis subsp. pinnatifida, along with four known glycosides, syringin, martynoside, leucosceptoside A and verbascoside. On the basis of chemical and spectral evidence the structures of darendoside A and B were determined as beta-(4-hydroxyphenyl)ethyl O-beta-D-apiofuranosyl-(1--&gt;2)-O-beta-D-glucopyranoside and beta-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-rhamnopyranosyl-(1--&gt;3)-O-beta-D-glucopyranoside (= deacyl martynoside), respectively.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2005
The leafy parts of thyme and its essential oil have been used in foods for its flavour, aroma and... more The leafy parts of thyme and its essential oil have been used in foods for its flavour, aroma and preservation for many years. In the present study the genotoxic potential of major compounds of thyme oil, i.e. thymol, carvacrol, and ␥-terpinene and of the methanolic extracts of thyme, were investigated in human lymphocytes by single-cell gel electrophoresis. Also, the effects of these substances on the induction of DNA damage by 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and mitomycin C (MMC) were evaluated. No increase in DNA strand breakage was observed at thymol and ␥-terpinene concentrations below 0.1 mM, but at the higher concentration of 0.2 mM significant increases in DNA damage were seen. Thymol and ␥-terpinene significantly reduced the DNA strand breakage induced by IQ and MMC at the lower concentrations studied. Carvacrol, which is an isomer of thymol, seemed to protect lymphocytes from the genotoxic effects of IQ and MMC at non-toxic concentrations below 0.05 mM, but at the higher concentration of 0.1 mM carvacrol itself induced DNA damage. Also the constituents of the n-hexane and ethyl acetate fractions prepared from the concentrated aqueous methanolic extracts of Thymus spicata protected lymphocytes against IQ-and MMC-induced DNA damage in a concentration-dependent manner.
The present study was carried out to investigate the modulating effects of thyme and its major co... more The present study was carried out to investigate the modulating effects of thyme and its major components against the oxidative DNA damage induced by H 2 O 2. The human lymphocytes with thymol, carvacrol, and γ-terpinene incubated with or without 0.1 mM H 2 O 2 for 30 min at 37°C and the DNA damage were evaluated by singe cell gel electropheresis (comet assay). Concentrations above 0.1 mM thymol and γ-terpinene and 0.05 mM carvacrol significantly induced DNA damage in human lymphocytes, but at the smaller concentrations no additional DNA strand breakage has been observed. At the all concentrations studied, γ-terpinene did not show any protective effect against H 2 O 2 induced oxidative DNA damage, but the phenolic compounds thymol and carvacrol at concentrations below 0.2 and 0.1 mM, respectively, significantly reduced the oxidative DNA damage (p < 0.001). The n-hexane and ethyl acetate fractions prepared from the methanolic extracts of Thymus spicata also were found to inhibit DNA damage.
Sepsis, often initiated by an infection, is a state of disrupted inflammatory homeostasis. There ... more Sepsis, often initiated by an infection, is a state of disrupted inflammatory homeostasis. There is increasing evidence that oxidative stress has an important role in the development of sepsis-induced multiorgan failure. Resveratrol (RV) is a polyphenolic compound found in the skin of red fruits, such as mulberries and red grapes, and in peanuts. RV has been reported to have an antioxidant, antiproliferative, and anti-inflammatory properties in various models. It has also been found to inhibit the proliferation of a variety of human cancer cell lines, including breast, prostate, colon, pancreatic, and thyroid. This study has been undertaken to assess the role of RV on the sepsis-induced oxidative DNA damage in the lymphocytes of Wistar albino rats by the standard and formamidopyrimidine DNA glycosylase (Fpg)-modified comet assays. The parameters of tail length, tail intensity, and tail moment were evaluated for the determination of DNA damage. According to the study, the DNA damage ...
The leafy parts of thyme and its essential oil have been used in foods for the flavour, aroma and... more The leafy parts of thyme and its essential oil have been used in foods for the flavour, aroma and preservation and also in folk medicines. In the present study the genotoxicity of thymol and carvacrol was examined using comet assay. In V79 Chinese hamster lung fibroblast cells treated with 1, 5, 25 microM thymol and carvacrol, only 25 microM thymol caused some clastogenic DNA damage. For detection of oxidative DNA damage, the comet assay with formamido pyrimidine glycosylase (Fpg) protein was used: When V79 cells were treated with 1, 5, 25 microM thymol and carvacrol and post-treated with Fpg enzyme, no significant increase of Fpg-sensitive sites was observed at all concentrations studied. Reactive oxygen species (ROS) generation decreased slightly in the presence of thymol (1-100 microM) and carvacrol (5 microM) between 1 and 4h, yet increased at the highest 100 microM concentration of carvacrol after 24h. Thymol and carvacrol displayed a concentration dependent antioxidant capacity, whilst gamma-terpinene which lacks a phenolic group did not show any antioxidant capacity in the trolox equivalent antioxidant capacity (TEAC) assay. The results of this study indicate a lack of clastogenic activity for thymol and carvacrol at biologically relevant concentrations, and a moderate antioxidant activity in vitro.
Two new phenylpropanoid glycosides, phlinosid~ D and E were isolated from the methanolic extract ... more Two new phenylpropanoid glycosides, phlinosid~ D and E were isolated from the methanolic extract of the aerial parts of Phlomis line&s, along with the known iridoid glucosides, lamiide, ipolamiide and auroside (= 5hydroxy-8epiloganin). On the basis of chemical and spectral evidence the structures of phlinosides D and E were determined as 3
The present study was carried out to investigate the modulating effects of thyme and its major co... more The present study was carried out to investigate the modulating effects of thyme and its major components against the oxidative DNA damage induced by H(2)O(2). The human lymphocytes with thymol, carvacrol, and gamma-terpinene incubated with or without 0.1 mM H(2)O(2) for 30 min at 37 degrees C and the DNA damage were evaluated by singe cell gel electropheresis (comet assay). Concentrations above 0.1 mM thymol and gamma-terpinene and 0.05 mM carvacrol significantly induced DNA damage in human lymphocytes, but at the smaller concentrations no additional DNA strand breakage has been observed. At the all concentrations studied, gamma-terpinene did not show any protective effect against H(2)O(2) induced oxidative DNA damage, but the phenolic compounds thymol and carvacrol at concentrations below 0.2 and 0.1 mM, respectively, significantly reduced the oxidative DNA damage (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The n-hexane and ethyl acetate fractions prepared from the methanolic extracts of Thymus spicata also were found to inhibit DNA damage.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2005
The leafy parts of thyme and its essential oil have been used in foods for its flavour, aroma and... more The leafy parts of thyme and its essential oil have been used in foods for its flavour, aroma and preservation for many years. In the present study the genotoxic potential of major compounds of thyme oil, i.e. thymol, carvacrol, and ␥-terpinene and of the methanolic extracts of thyme, were investigated in human lymphocytes by single-cell gel electrophoresis. Also, the effects of these substances on the induction of DNA damage by 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) and mitomycin C (MMC) were evaluated. No increase in DNA strand breakage was observed at thymol and ␥-terpinene concentrations below 0.1 mM, but at the higher concentration of 0.2 mM significant increases in DNA damage were seen. Thymol and ␥-terpinene significantly reduced the DNA strand breakage induced by IQ and MMC at the lower concentrations studied. Carvacrol, which is an isomer of thymol, seemed to protect lymphocytes from the genotoxic effects of IQ and MMC at non-toxic concentrations below 0.05 mM, but at the higher concentration of 0.1 mM carvacrol itself induced DNA damage. Also the constituents of the n-hexane and ethyl acetate fractions prepared from the concentrated aqueous methanolic extracts of Thymus spicata protected lymphocytes against IQ-and MMC-induced DNA damage in a concentration-dependent manner.
Two new phenethyl alcohol glycosides, darendoside A and B (= deacyl martynoside) were isolated fr... more Two new phenethyl alcohol glycosides, darendoside A and B (= deacyl martynoside) were isolated from the methanolic extract of the aerial parts of Scutellaria orientalis subsp. pinnatifida, along with four known glycosides, syringin, martynoside, leucosceptoside A and verbascoside. On the basis of chemical and spectral evidence the structures of darendoside A and B were determined as beta-(4-hydroxyphenyl)ethyl O-beta-D-apiofuranosyl-(1--&gt;2)-O-beta-D-glucopyranoside and beta-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-rhamnopyranosyl-(1--&gt;3)-O-beta-D-glucopyranoside (= deacyl martynoside), respectively.
The present study was carried out to investigate the modulating effects of the two flavonoids que... more The present study was carried out to investigate the modulating effects of the two flavonoids quercetin and rutin on the mutagenic anticancer drug mitomycin C by single cell gel electrophoresis (Comet assay) in human lymphocytes. Lymphocytes were incubated with different concentrations of quercetin and rutin, with or without mitomycin C, and DNA damage was evaluated. Concentrations of 0.03, 0.15, 0.3, 0.6, 1.5 and 3mM quercetin significantly reduced the DNA strand breakage induced by mitomycin C (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) but the highest concentration of 6mM quercetin did not show a protective effect. The frequency of damaged cells induced by mitomycin C was not changed at 0.02 mM, and also at the highest concentrations of 1.64 and 3.28 mM rutin. However, at concentrations of 0.08, 0.16, 0.33 and 0.82 mM rutin cells were protected from DNA damage. Thus, in human lymphocytes quercetin and rutin displayed protective effects on DNA damage induced by mitomycin C, in a concentration-dependent manner.
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