Biomedical subjects

Piero Dolara

Publications and source records attributed to Piero Dolara.

At least 19 recordsLinked to original sources

PubMed2006

Daily consumption of a high-phenol extra-virgin olive oil reduces oxidative DNA damage in postmenopausal women.

Extra-virgin olive oils (EVOO), high in phenolic compounds with antioxidant properties, could be partly responsible for the lower mortality and incidence of cancer and CVD in the Mediterranean region. The present study aims to measure oxidative DNA damage in healthy human subjects consuming olive oils with different concentrations of natural phenols. A randomised cross-over trial of high-phenol EVOO (high-EVOO; 592 mg total phenols/kg) v. low-phenol EVOO (low-EVOO; 147 mg/kg) was conducted in ten postmenopausal women in Florence. Subjects were asked to substitute all types of fat and oils habitually consumed with the study oil (50 g/d) for 8 weeks in each period. Oxidative DNA damage was measured by the comet assay in peripheral blood lymphocytes, collected at each visit during the study period. Urine samples over 24 h were collected to measure the excretion of the olive oil phenols. The average of the four measurements of oxidative DNA damage during treatment with high-EVOO was 30 % lower than the average during the low-EVOO treatment (P=0.02). Urinary excretion of hydroxytyrosol and its metabolite homovanillyl alcohol were significantly increased in subjects consuming high-EVOO. Despite the small sample size, the present study showed a reduction of DNA damage by consumption of an EVOO rich in phenols, particularly hydroxytyrosol.

Aged↗

PubMed2006

Calibration of the comet assay for the measurement of DNA damage in mammalian cells.

We used X-rays from a linear accelerator and from a low energy therapeutic source to calibrate the single cell gel electrophoresis (comet assay), a widely used method to measure DNA damage. Gamma-rays from 60Co, with known efficiency in inducing DNA breakage, were used as reference. Human lymphocytes and one murine tumour cell line, F10-M3 cells, were irradiated under different experimental conditions. A similar relationship between radiation dose and induced DNA damage was obtained with gamma- and X-rays. A calibration curve was constructed to convert the comet assay raw data into break frequency. The median levels of DNA breaks and oxidative damage in circulating lymphocytes from healthy volunteers were calculated to be 0.76 and 0.80 breaks/10(9) Da, respectively, (0.50 and 0.52 breaks/10(6) bp). The values of oxidative DNA damage were in the same order of magnitude as those found by others with HPLC methods.

Adult↗

PubMed2005

Red wine polyphenols influence carcinogenesis, intestinal microflora, oxidative damage and gene expression profiles of colonic mucosa in F344 rats.

Polyphenols from tea and other beverages such as red wine have been regarded with interest as possible chemopreventive agents against cancer. Here we report that red wine polyphenols (50 mg/kg) administered with the diet to F344 rats for 16 weeks inhibited colon carcinogenesis induced by azoxymethane (AOM, 7.4 mg/kg, total dose 74 mg/kg) or dimethylhydrazine (DMH, 30 mg/kg, total dose, 300 mg/kg). Polyphenol-treated animals had a consistently lower tumour yield compared to controls. In polyphenol-treated rats, the main bacterial strains in the faeces at sacrifice were Bacteroides, Lactobacillus and Bifidobacterium spp., whereas microorganisms predominantly identified in control-fed rats were Bacteroides, Clostridium and Propionibacterium spp. Wine polyphenols (57 mg/kg for 10 days, by gavage), administered to rats not treated with carcinogens, produced a significant decrease in the basal level of DNA oxidative damage of the colon mucosa as measured with the comet assay (average pyrimidine oxidation was reduced by 62% and purine oxidation by 57%, p<0.05). To further explore the molecular effects of wine polyphenols we used the microarray technology to study gene expression profiles: rats were treated with 50 mg/kg wine polyphenols for 14 days, mixed in the diet. Global expression analysis of 5707 genes revealed an extensive down-regulation of genes involved in a wide range of physiological functions, such as metabolism, transport, signal transduction and intercellular signalling. By analysing metabolic pathways with the GenMAPP software program we observed that two major regulatory pathways were down-regulated in the colon mucosa of polyphenols-treated rats: inflammatory response and steroid metabolism. We also found a down-regulation of many genes regulating cell surface antigens, metabolic enzymes and cellular response to oxidative stress. In conclusion, reduction of oxidative damage, modulation of colonic flora and variation in gene expression may all concur in the modulation of intestinal function and carcinogenesis by wine polyphenols.

1,2-Dimethylhydrazine↗

PubMed2005

Mucin-depleted foci have beta-catenin gene mutations, altered expression of its protein, and are dose- and time-dependent in the colon of 1,2-dimethylhydrazine-treated rats.

Mucin-depleted foci (MDF) are purported preneoplastic lesions that can be easily visualized in the unsectioned colon of carcinogen-treated rats stained with high-iron diamine alcian blue (HID-AB). In F344 rats treated twice with 150 mg/kg of 1,2-dimethylhydrazine (DMH) and sacrificed after 5, 9, 13 and 28 weeks, MDF increased over time from 5 to 13 weeks, whereas they decreased at 28 weeks, when tumors appear. MDF multiplicity (crypts/MDF) linearly increased with time. Increasing doses of DMH (100, 150 and 200 mg/kg x 2 times) caused a dose-related increase in MDF. Mutations in Ctnnb1 gene codifying for beta-catenin were identified with PCR amplification and direct sequencing in 6/15 tumors (40%), 7/28 MDF (25%) and 2/27 (7%) aberrant crypt foci (ACF) identified in HID-AB-stained colon. All mutations in tumors and MDF caused amino acid substitution, while one mutation in ACF was silent. Beta-catenin detected at membrane level by immunohistochemistry was markedly reduced in MDF and tumors and, to a lesser extent, in ACF identified with HID-AB. By contrast, nuclear localization of beta-catenin was significantly increased in MDF and tumors, while no variation was observed in ACF. Beta-catenin cytoplasmic expression was also significantly increased in MDF and tumors but to a lesser extent in ACF. In conclusion, MDF are induced dose-dependently by DMH, increase in size with time, have mutations in the beta-catenin gene and marked alterations in beta-catenin cellular localization. Since all these phenomena are considered specific steps for colon tumorigenesis, these results further support the hypothesis that MDF are cancer precursors and can be proposed as endpoints in short-term carcinogenesis experiments.

1,2-Dimethylhydrazine↗

PubMed2005

Seasonal variations of DNA damage in human lymphocytes: correlation with different environmental variables.

Several types of DNA damage, including DNA breaks and DNA base oxidation, display a seasonal trend. In the present work, a sample of 79 healthy subjects living in the city of Florence, Italy, was used to analyse this effect. Three possible causative agents were taken into consideration: solar radiation, air temperature and air ozone level. DNA damage was measured in isolated human lymphocytes at different times during the year and the observed damage was correlated with the levels of these three agents in the days preceding blood sampling. Three time windows were chosen: 3, 7 and 30 days before blood sampling. DNA strand breaks and the oxidized purinic bases cleaved by the formamidopyrimidine glycosylase (FPG sites) were measured by means of the comet assay. The results of multivariate regression analysis showed a positive correlation between lymphocyte DNA damage and air temperature, and a less strong correlation with global solar radiation and air ozone levels.

Adult↗

PubMed2005

The comet assay approach to senescent human diploid fibroblasts identifies different phenotypes and clarifies relationships among nuclear size, DNA content, and DNA damage.

The comet assay methodology was used to monitor nuclear changes occurring in MRC5 human fibroblasts during transition from young to senescent cultures and to study heterogeneity of senescent populations. Nuclear morphology and size, DNA content per nucleus, and DNA damage (basal strand break, total damage, and oxidized base levels) were evaluated; moreover, visually identified large and small nuclei were analyzed separately and arranged in classes of increasing DNA damage. Oxidized base levels were definitely lower in young versus senescent fibroblasts of which, however, a significant proportion showed negligible DNA damage. Nuclear size enlargement accompanying senescence was almost equally influenced by cell ploidy increase and also by a chromatin decondensation process involving diploid cells. It is noteworthy that DNA damage in senescent fibroblasts correlated significantly to nuclear size, but not to DNA content. The comet assay allowed us to identify different senescent phenotypes and to investigate changes in nuclear features and/or DNA damage irrespective of time elapsed in culture.

Cell Nucleus↗

PubMed2005

Active and passive smoking and lifestyle determinants of 8-oxo-7,8-dihydro-2'-deoxyguanosine levels in human leukocyte DNA.

We investigated the effects of smoking and exposure to environmental tobacco smoke (ETS) on oxidative DNA damage by measuring 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels in DNA of leukocytes of healthy donors (30 smokers, 29 nonsmokers, and 28 ETS-exposed subjects). Nonsmokers had lower 8-oxodGuo levels compared with smokers (5.94 +/- 0.87 x 10(-6) and 19.85 +/- 4.75 x 10(-6) 2-deoxyguanosine, respectively, means +/- SE, P = 0.00007). Subjects exposed to ETS had higher mean value of 8-oxodGuo compared with nonsmokers (9.18 +/- 1.53 x 10(-6) 2-deoxyguanosine, mean +/- SE), nonsignificant by univariate analysis (P = 0.074). Multiregression analysis indicated that the increase of 8-oxodGuo levels induced by ETS was significant (P = 0.045) and that coffee and tea consumption reduced DNA oxidation (P = 0.0053). Oxidative leukocyte DNA damage was positively correlated with plasma cotinine levels in ETS-exposed subjects (r = 0.47, P < 0.01, n = 28) and was increased by age in nonsmokers and ETS-exposed subjects (P = 0.049). The results seem to confirm that ETS exposure is capable of inducing some oxidative DNA damage in circulating leukocytes and that coffee and tea consumption might partially protect against smoking-induced oxidation damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

Extremely low-frequency electromagnetic fields do not affect DNA damage and gene expression profiles of yeast and human lymphocytes.

We studied the effects of extremely low-frequency (50 Hz) electromagnetic fields (EMFs) on peripheral human blood lymphocytes and DBY747 Saccharomyces cerevisiae. Graded exposure to 50 Hz magnetic flux density was obtained with a Helmholtz coil system set at 1, 10 or 100 microT for 18 h. The effects of EMFs on DNA damage were studied with the single-cell gel electrophoresis assay (comet assay) in lymphocytes. Gene expression profiles of EMF-exposed human and yeast cells were evaluated with DNA microarrays containing 13,971 and 6,212 oligonucleotides, respectively. After exposure to the EMF, we did not observe an increase in the amount of strand breaks or oxidated DNA bases relative to controls or a variation in gene expression profiles. The results suggest that extremely low-frequency EMFs do not induce DNA damage or affect gene expression in these two different eukaryotic cell systems.

Blood Proteins↗

PubMed2004

Increased oxidative DNA damage in mononuclear leukocytes in vitiligo.

Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo.

Adolescent↗

PubMed2004

Loss of tyrosinase activity confers increased skin tumor susceptibility in mice.

The tyrosinase (Tyr) gene encodes the enzyme tyrosinase that catalyses the conversion of L-tyrosine into DOPA (3,4-dihydroxyphenylalanine)-quinone. The albino mutation abrogates functional activity of tyrosinase resulting in deficiency of melanin pigment production in skin and retina. Tyr maps to a region in the central position of Chromosome 7 that contains a skin tumor-modifier locus. We rescued the albino mutation in transgenic mice to assess a possible role of Tyr gene in two-stage skin carcinogenesis. Transgenic expression of the functional Tyr(Cys) allele in albino mice (Tyr(Ser)) caused a reduction in skin papilloma multiplicity, in four independent experiments and at three dose levels of DMBA (9,10-dimethyl-1,2-benzanthracene). In vitro mechanistic studies demonstrated that transfection of the Tyr(Cys) allele in a human squamous cell carcinoma cell line (NCI-H520) increases tyrosinase enzyme activity and confers resistance to hydrogen peroxide-induced oxidative DNA damage. These results provide direct evidence that the Tyr gene can act as a skin cancer-modifier gene, whose mechanism of action may involve modulation of oxidative DNA damage.

Albinism↗

PubMed2004

Effect of polyphenolic extracts from red wine and 4-OH-coumaric acid on 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.

BACKGROUND: Total polyphenolic extracts from red wine protect against azoxymethane (AOM)-induced colon carcinogenesis in rats. Since red wine contains more than 200 different polyphenolic compounds, it is still unclear which substances are responsible for this effect. AIM OF THE STUDY: We investigated the effect of high molecular weight polyphenols (HMWP), low molecular weight polyphenols (LMWP) and total polyphenolic extracts from red wine (WE) on colon carcinogenesis. We also tested the effect of 4-OH-coumaric acid, a potent phenolic antioxidant present in wine and fruit. METHODS: F344 rats were treated weekly with 1,2-dimethylhydrazine (DMH) (30 mg/kg b.w. subcutaneously x 10 times). One week after the final DMH injection rats were divided into five groups and fed: a) a high fat (HF) diet containing 23% corn oil (w/w), as control or the same basal diet supplemented with b) 0.11 % (w/w) WE; c) 0.027% (w/w) HMWP d) 0.083% (w/w) LMWP or e) 0.1 % (w/w) 4-OH-coumaric acid. The dietary treatments continued until sacrifice, 16 weeks after the last DMH injection. RESULTS: WE treated rats had significantly fewer (p < 0.05) colorectal adenomas than controls, while rats in other treatment groups did not differ significantly from controls (colorectal adenomas/rat were: 2.2 +/- 0.3; 1.4 +/- 0.2; 2.9 +/- 0.5; 2.6 +/- 0.4; 2.3 +/- 0.3; in controls, WE, HMWP, LMWP and 4-OH-coumaric acid groups, respectively; means +/- SE). The mean number of colorectal carcinomas per rat was similar among all experimental groups. Proliferative activity in the normal colon mucosa did not vary among experimental groups. CONCLUSIONS: Total polyphenolic extracts (WE) from red wine, but neither the HMWP nor the LMWP, have some inhibitory effect on the process of colon carcinogenesis by DMH reducing the number of adenomas.

1,2-Dimethylhydrazine↗

PubMed2004

Benzo(a)pyrene diolepoxide (BPDE)-DNA adduct levels in leukocytes of smokers in relation to polymorphism of CYP1A1, GSTM1, GSTP1, GSTT1, and mEH.

Benzo(a)pyrene [B(a)P] diolepoxide (BPDE)-DNA adducts were measured in the leukocytes of 41 healthy smokers using high-performance liquid chromatography coupled with a fluorimetric detector. The correlation between exposure to B(a)P through smoking and BPDE-DNA adduct levels was poor (r = 0.31), although subjects in the high exposure group [B(a)P > 50 ng/d] had a slightly higher level of adducts compared with the less exposed group (mean +/- SE, 1.70 +/- 0.3 versus 1.09 +/- 0.1; P = 0.057). We studied the effect on BPDE-DNA adducts of individual variations in genes controlling B(a)P metabolism, classifying subjects in "low-risk" and "high-risk" genotypes for smoking-related B(a)P DNA damage. The high-risk group included subjects characterized by a combination of increased B(a)P activation [cytochrome P450 1A1 (CYP1A1) MspI and/or exon 7 Ile462Val allele variants and microsomal epoxide hydrolase (mEH) fast activity] and decreased deactivation ability [presence of glutathione S-transferase M1 (GSTM1) null allele and wild-type glutathione S-transferase P1 (GSTP1)]. The low-risk group included smokers with lower B(a)P activation (wild-type CYP1A1, low or intermediate mEH activity) and higher deactivation capacity (active GSTM1, GSTP1 Ile105Val allele). Subjects in the low-risk group had lower levels of BPDE-DNA adducts compared with subjects in the high-risk genotype group; this difference was significant using two markers (CYP1A1 and GSTM1, median +/- SD, 0.77 +/- 1.16 versus 1.89 +/- 0.39; P = 0.03) or three markers (CYP1A1, GSTM1, and GSTP1, median +/- SD, 0.66 +/- 0.93 versus 1.43 +/- 1.17; P = 0.013). The discrimination between groups was reduced when including mEH as an additional marker (P = 0.085). In conclusion, CYP1A1, GSTM1, and GSTP1 genotyping seems to be a risk predictor of BPDE-DNA adduct formation in leukocytes.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed2003

Mucin-depleted foci (MDF) in the colon of rats treated with azoxymethane (AOM) are useful biomarkers for colon carcinogenesis.

Crypt foci with absent or scant mucous production (mucin-depleted foci, MDF) were recently described by our group in the colon of azoxymethane (AOM)-treated rats. Since MDF are dysplastic and easy to quantify, we think that MDF are pre-neoplastic lesions that could be used as biomarkers for carcinogenesis. To test this hypothesis, we studied MDF in azoxymethane (AOM)-initiated rats treated with cholic acid (CHA), a promoter of colon carcinogenesis or with piroxicam (PXC), a colon cancer-inhibiting drug. Aberrant crypt foci (ACF) were determined as well. F344 male rats were treated with AOM (15 mg/kg x 2, s.c.) and then divided into: controls, which were fed AIN76 diet; CHA group, which was fed AIN76 diet containing CHA 0.5% w/w; PXC group, which was fed AIN76 diet containing PXC 0.02% w/w. Ten weeks after the first dose of AOM, the total number of MDF was significantly increased in rats treated with CHA (P<0.05) and drastically reduced (P<0.01) in rats treated with PXC (MDF/colon were 6.10 +/- 1.26, 10.59 +/- 1.96 and 1.31 +/- 0.21 in controls, CHA and PXC groups, respectively, means +/- SE). The multiplicity of MDF was also increased in CHA-treated rats. On the contrary, ACF multiplicity was significantly decreased by CHA. In PXC-treated rats there were fewer ACF with lower multiplicity. The effect of PXC was also investigated 15 weeks after the first AOM dose and the results showed that the total number of MDF in the PXC group was significantly lower than in controls. The number of 'large' MDF, formed by 12 or more crypts, was also reduced (P<0.01) by PXC ('large' MDF were 1.7 +/- 0.5 and 0.4 +/- 0.2 in control and PXC groups, respectively). Since CHA promotes and PXC reduces colon cancer, MDF are correlated with carcinogenesis and can be proposed as endpoints to study the modulation of colon carcinogenesis in short-term experiments.

Animals↗

PubMed2003

Oxidative DNA damage in peripheral blood cells in type 2 diabetes mellitus: higher vulnerability of polymorphonuclear leukocytes.

Since oxidative stress is thought to play an important role in the pathogenesis and complications of diabetes, we used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as FPG (formamidopyrimidine DNA glycosylase)-sensitive sites, in peripheral blood cells (PBC) from type 2 diabetes patients and healthy controls. Oxidative DNA damage in leukocytes was increased in diabetic compared to normal subjects. However, no differences in the levels of DNA damage in isolated lymphocytes were found between the two groups. These data indicate a higher vulnerability to oxidative damage of polymorphonuclear as compared to mononuclear leukocytes in type 2 diabetes. Thus, the measurement of oxidative DNA damage in leukocytes by means of the comet assay is a suitable marker for the evaluation of systemic oxidative stress in diabetic patients.

Blood Cells↗

PubMed2003

Measurement of DNA breaks and oxidative damage in polymorphonuclear and mononuclear white blood cells: a novel approach using the comet assay.

DNA damage is thought to play a relevant role in degenerative diseases and aging. Therefore, measuring DNA damage in living cells without artifacts is a critical issue, especially with very sensitive methods, such as the comet assay, which can detect very low levels of DNA damage. We show here that the procedures of cell subtype isolation increase DNA damage measured in human white blood cells (WBC) with the comet assay. We describe a novel and simple method to measure DNA strand breaks and oxidative damage separately in polymorphonuclear and mononuclear leukocytes, using whole blood without previous cell isolation. This method can be useful for measuring DNA damage in different subtypes of human peripheral leukocytes, avoiding the artifacts and the time involved in the cell separation procedures.

Cell Separation↗

PubMed2003

Identification of mucin-depleted foci in the unsectioned colon of azoxymethane-treated rats: correlation with carcinogenesis.

We tested the association between aberrant crypt foci (ACF) and tumor induction by feeding azoxymethane-induced rats (15 mg/kg x 2, s.c.) with synbiotics (Raftilose Synergy 1, a derivative of inulin, 10% of the diet, along with lactobacilli and bifidobacteria). After 16 weeks of feeding, synbiotics significantly increased ACF multiplicity. On the contrary, after 32 weeks, synbiotics significantly decreased intestinal tumors. When the same unsectioned colon used for ACF determination was stained with high-iron diamine Alcian blue, foci of crypts with scarce or absent mucins were identified. We defined these lesions as mucin-depleted foci (MDF), and they were visible in all azoxymethane-treated rats and correlated with tumor induction (MDF/colon: 8.2 +/- 0.9 and 3.8 +/- 0.9 in controls and synbiotic-fed rats, respectively, P < 0.01; crypts/MDF: 12.2 +/- 2 and 6.4 +/- 1 in controls and synbiotic-fed rats, respectively, P < 0.05, means +/- SE, n = 7). There were fewer MDF/colon than ACF, and they were histologically more dysplastic than mucinous lesions identified as ACF in high-iron diamine Alcian blue-stained colon. In conclusion, MDF may be premalignant lesions that predict colon carcinogenesis.

Animals↗

PubMed2003

Vulnerability to DNA damage in the aging rat substantia nigra: a study with the comet assay.

Oxidative DNA damage was measured in the substantia nigra (SN), cortex, hippocampus, striatum and hypothalamus of 3- and 24-month-old rats, using single-cell gel electrophoresis (SCGE, 'comet' assay) which allows the detection of DNA breaks and oxidized bases. A significant increase in basal DNA damage was selectively found in the SN of aged rats. FPG-sensitive oxidative DNA damage was also significantly increased in the SN of aged rats and, to a lesser extent, in the cortex and hypothalamus. These data show a higher vulnerability of SN to oxidative damage with aging and indicate that the detection of DNA damage within discrete brain nuclei can provide a reliable tool for investigating oxidative damage in neurodegenerative processes.

Aging↗

PubMed2003

Protection against ultraviolet B-induced oxidative DNA damage in rabbit corneal-derived cells (SIRC) by 4-coumaric acid.

The exposure of cells to ultraviolet B radiation (UV-B) can induce the production of reactive oxygen species (ROS) which damage cellular components. Free radical scavengers and antioxidants can interfere with the production of ROS. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, a marker of oxidative DNA damage in rabbit corneal-derived cells (SIRC) exposed to UV-B in the presence of 4-coumaric acid, a natural polyphenol. The levels of 8-OHdG were increased significantly (P<0.01) following irradiation (from 12+/-1.2x10(-6) to 29+/-6.2x10(-6) dG, means+/-SE). When 10 microM 4-coumaric acid was added to the medium, 8-OHdG levels were similar to those of unexposed cells (16.8+/-0.8x10(-6) dG). UV-B irradiation decreased superoxide dismutase (SOD) activity in SIRC cells from 0.29+/-0.6 to 0.15+/-0.04 mU/mg (means+/-SE). The presence of 10 microM 4-coumaric acid prevented the decrease in SOD activity (0.20+/-0.05 mU/mg, P<0.05). On the contrary, SIRC cells exposed to UV-B had higher levels of xanthine oxidase (XO) activity compared with control ones (0.40+/-0.07 and 0.24+/-0.08 mU/mg, means+/-SE, respectively). In the presence of 10 microM 4-coumaric acid, the increase in XO activity was prevented (0.16+/-0.03 mU/mg; mean+/-SE). In conclusion, UV-B-induced oxidative DNA damage in SIRC cells is inhibited by 4-coumaric acid, which, probably through its free radical scavenging activity, stabilizes SOD activity and blocks the increase of XO activity following UV-B irradiation. Thus, the topical use of 4-coumaric acid may prevent free radical damage in the cornea.

8-Hydroxy-2'-Deoxyguanosine↗