An In Vitro Study on the Interactions of Pycnogenol® with Cisplatin in Human Cervical Cancer Cells.

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 IC50 values of cisplatin were 22.4 µM and 12.3 µM for 24 h and 48 h, respectively. The IC50 values of PYC were 261 µM and 213 µM for 24 h and 48 h, respectively. For 24 h exposure, PYC significantly reduced the IC50 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 H2O2-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.

Evaluation of the DNA damage in lymphocytes, sperm and buccal cells of workers under environmental and occupational boron exposure conditions.

Industrial production and use of boron compounds have increased during the last decades, especially for the manufacture of borosilicate glass, fiberglass, metal alloys and flame retardants. This study was conducted in two districts of Balikesir; Bandirma and Bigadic, which geographically belong to the Marmara Region of Turkey. Bandirma is the production and exportation zone for the produced boric acid and some borates and Bigadic has the largest B deposits in Turkey. 102 male workers who were occupationally exposed to boron from Bandirma and 110 workers who were occupationally and environmentally exposed to boron from Bigadic participated to our study. In this study the DNA damage in the sperm, blood and buccal cells of 212 males was evaluated by comet and micronucleus assays. No significant increase in the DNA damage in blood, sperm and buccal cells was observed in the residents exposed to boron both occupationally and environmentally (p = 0.861) for Comet test in the sperm samples, p = 0.116 for Comet test in the lymphocyte samples, p = 0.042 for micronucleus (MN) test, p = 0.955 for binucleated cells (BN), p = 1.486 for condensed chromatin (CC), p = 0.455 for karyorrhectic cells (KHC), p = 0.541 for karyolitic cells (KLY), p = 1.057 for pyknotic cells (PHC), p = 0.331 for nuclear bud (NBUD)). No correlations were seen between blood boron levels and tail intensity values of the sperm samples, lymphocyte samples, frequencies of MN, BN, KHC, KYL, PHC and NBUD. The results of this study came to the same conclusions of the previous studies that boron does not induce DNA damage even under extreme exposure conditions.

Boron-exposed male workers in Turkey: no change in sperm Y:X chromosome ratio and in offspring's sex ratio.

Boron-associated shifts in sex ratios at birth were suggested earlier and attributed to a decrease in Y- vs. X-bearing sperm cells. As the matter is pivotal in the discussion of reproductive toxicity of boron/borates, re-investigation in a highly borate-exposed population was required. In the present study, 304 male workers in Bandirma and Bigadic (Turkey) with different degrees of occupational and environmental exposure to boron were investigated. Boron was quantified in blood, urine and semen, and the persons were allocated to exposure groups along B blood levels. In the highest ("extreme") exposure group (n = 69), calculated mean daily boron exposures, semen boron and blood boron concentrations were 44.91 ± 18.32 mg B/day, 1643.23 ± 965.44 ng B/g semen and 553.83 ± 149.52 ng B/g blood, respectively. Overall, an association between boron exposure and Y:X sperm ratios in semen was not statistically significant (p > 0.05). Also, the mean Y:X sperm ratios in semen samples of workers allocated to the different exposure groups were statistically not different in pairwise comparisons (p > 0.05). Additionally, a boron-associated shift in sex ratio at birth towards female offspring was not visible. In essence, the present results do not support an association between boron exposure and decreased Y:X sperm ratio in males, even under extreme boron exposure conditions.

Preventive role of Pycnogenol® against the hyperglycemia-induced oxidative stress and DNA damage in diabetic rats.

Diabetes mellitus, a complex progressive metabolic disorder, leads to some oxidative stress related complications. Pycnogenol® (PYC), a plant extract obtained from Pinus pinaster, has been suggested to be effective in many diseases including diabetes, cancer, inflammatory and immune system disorders. The mechanisms underlying the effects of PYC in diabetes need to be elucidated. The aim of this study was to determine the effects of PYC treatment (50 mg/kg/day, orally, for 28 days) on the DNA damage and biochemical changes in the blood, liver, and kidney tissues of experimental diabetic rats. Changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase enzymes, and the levels of 8-hydroxy-2'-deoxyguanosine, total glutathione, malondialdehyde, insulin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, high density lipoprotein, low density lipoprotein, total cholesterol, and triglyceride were evaluated. DNA damage was also determined in the whole blood cells and the liver and renal tissue cells using the alkaline comet assay. PYC treatment significantly ameliorated the oxidative stress, lipid profile, and liver function parameters as well as DNA damage in the hyperglycemic rats. The results show that PYC treatment might improve the hyperglycemia-induced biochemical and physiological changes in diabetes.

An In Vitro Study on the Cytotoxicity and Genotoxicity of Silver Sulfide Quantum Dots Coated with Meso-2,3-dimercaptosuccinic Acid.

OBJECTIVES: Silver sulfide (Ag2S) quantum dots (QDs) are highly promising nanomaterials in bioimaging systems due to their high activities for both imaging and drug/gene delivery. There is insufficient research on the toxicity of Ag2S QDs coated with meso-2,3-dimercaptosuccinic acid (DMSA). In this study, we aimed to determine the cytotoxicity of Ag2S QDs coated with DMSA in Chinese hamster lung fibroblast (V79) cells over a wide range of concentrations (5-2000 µg/mL). MATERIALS AND METHODS: Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays. The genotoxic and apoptotic effects of DMSA/Ag2S QDs were also assessed by comet assay and real-time polymerase chain reaction technique, respectively. RESULTS: Cell viability was 54.0±4.8% and 65.7±4.1% at the highest dose (2000 µg/mL) of Ag2S QDs using the MTT and NRU assays, respectively. Although cell viability decreased above 400 µg/mL (MTT assay) and 800 µg/mL (NRU assay), DNA damage was not induced by DMSA/Ag2S QDs at the studied concentrations. The mRNA expression levels of p53, caspase-3, caspase-9, Bax, Bcl-2, and survivin genes were altered in the cells exposed to 500 and 1000 µg/mL DMSA/Ag2S QDs. CONCLUSION: The cytotoxic effects of DMSA/Ag2S QDs may occur at high doses through the apoptotic pathways. However, DMSA/Ag2S QDs appear to be biocompatible at low doses, making them well suited for cell labeling applications.

Evaluation of FSH, LH, testosterone levels and semen parameters in male boron workers under extreme exposure conditions.

Boric acid and sodium borates are currently classified in the EU-CLP regulation as "toxic to reproduction" under "Category 1B", with hazard statement of H360FD. However, so far field studies on male reproduction in China and in Turkey could not confirm such boron-associated toxic effects. As validation by another independent study is still required, the present study has investigated possible boron-associated effects on male reproduction in workers (n = 212) under different boron exposure conditions. The mean daily boron exposure (DBE) and blood boron concentration of workers in the extreme exposure group (n = 98) were 47.17 ± 17.47 (7.95-106.8) mg B/day and 570.6 ± 160.1 (402.6-1100) ng B/g blood, respectively. Nevertheless, boron-associated adverse effects on semen parameters, as well as on FSH, LH and total testosterone levels were not seen, even within the extreme exposure group. With this study, a total body of evidence has accumulated that allows to conclude that male reproductive effects are not relevant to humans, under any feasible and realistic conditions of exposure to inorganic boron compounds.

Effects of silver sulfide quantum dots coated with 2-mercaptopropionic acid on genotoxic and apoptotic pathways in vitro.

Quantum dots (QDs) are highly promising nanomaterials in bioimaging system because of their bright fluorescence, broad UV excitation, narrow emission band, and high photostability. Recently, there is a great activity on Ag2S quantum dots for both imaging and drug/gene delivery due to the potential of having a better cytocompatability and near infrared luminescence. 2-Mercaptopropionic acid (2 MP A)-coated silver sulfide (Ag2S) QDs were reported as the most luminescent, stable, anionic Ag2S QDs in the literature. In this study, we aim to determine the cytotoxicity of 2 MP A/Ag2S in Chinese hamster lung fibroblast (V79) cells. The genotoxic and apoptotic effects of 2 MP A/Ag2S QDs were assessed by the alkaline single cell electrophoresis assay and real time polymerase chain reaction techniques, respectively. The cell viability decreased above 200 µg/ml and 800 µg/ml for MTT tetrazolium and neural red uptake assays, respectively. DNA damage was not observed by 2 MP A/Ag2S QDs at the studied concentration levels (5-2000 µg/ml). The levels of mRNA expression of p53, caspase 3, caspase 9, bax, bcl-2, survivin were not changed by 2 MP A/Ag2S QDs below IC50 (around 1000 µg/ml). Hence, 2 MP A/Ag2S QDs did not show any cytotoxic or genotoxic effects in V79 cells at lower doses. We conclude that the biocompatibility of 2 MP A/Ag2SODs makes them suitable for cell labeling applications.

Birth weights of newborns and pregnancy outcomes of environmentally boron-exposed females in Turkey.

Boric acid and sodium borates are currently classified as being toxic to reproduction under "Category 1B" with the hazard statement of "H360 FD" in the European CLP regulation. This has prompted studies on boron-mediated reprotoxic effects in male workers in boron mining areas and boric acid production plants. By contrast, studies on boron-mediated developmental effects in females are scarce. The present study was designed to fill this gap. Hundred and ninety nine females residing in Bandirma and Bigadic participated in this study investigating pregnancy outcomes. The participants constituted a study group covering blood boron from low (< 100 ng B/g blood, n = 143) to high (> 150 ng B/g blood, n = 27) concentrations. The mean blood boron concentration and the mean estimated daily boron exposure of the high exposure group was 274.58 (151.81-975.66) ng B/g blood and 24.67 (10.47-57.86) mg B/day, respectively. In spite of the high level of daily boron exposure, boron-mediated adverse effects on induced abortion, spontaneous abortion (miscarriage), stillbirth, infant death, neonatal death, early neonatal death, preterm birth, congenital anomalies, sex ratio and birth weight of newborns were not observed.

Effects of cinnamic acid on complications of diabetes

Background/aim: Diabetes mellitus (DM) is a major health problem worldwide. Cinnamic acid (CA) and its derivatives are synthesized in plants and increasing attention has been given to them in recent years due to the high number of beneficial health properties attributed to their consumption. The aim of this study was to investigate the effects of CA on streptozotocin-induced diabetes in Wistar albino rats. Materials and methods: DNA damage was evaluated in the blood, liver, and kidney cells of rats by the alkaline comet assay. Oxidative stress parameters such as catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase activities and 8-hydroxy-2-deoxyguanosine, total glutathione, and malondialdehyde levels; biochemical parameters including insulin, total bilirubin, and BCA protein levels; hepatic enzyme levels such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase; and lipid profile parameters including high-density lipoprotein, low-density lipoprotein, total cholesterol, and triglyceride levels were also evaluated. Results: DM caused genotoxic damage and alterations in lipid profiles, oxidative stress parameters, and hepatic enzymes levels. CA treatment ameliorated these effects. Conclusion: It seems that CA might have a role in the prevention of the complications of diabetes.

In vitro genotoxicity assessment of dinitroaniline herbicides pendimethalin and trifluralin.

Pendimethalin and trifluralin are widely used dinitroaniline herbicides. Both compounds can be found as residue levels in agricultural products. This study was conducted in order to provide necessary information for the risk assessment of pendimethalin and trifluralin. In this study, reactive oxygen species (ROS) levels were measured to examine the potential of both compounds to induce oxidative damage in Chinese hamster lung fibroblast (V79) cells. Also, the genotoxic effects of pendimethalin and trifluralin at the concentration range of 1-500 µM was determined. Single cell gel electrophoresis (comet) and micronucleus assays were used on human peripheral lymphocytes and V79 cells for the genotoxicity assessment. The cell viability of two dinitroaniline herbicides were determined by the use of neutral red uptake assay on V79 cells. IC50 values were determined as 66 µM and 128 µM for pendimethalin and trifluralin, respectively. They significantly increased ROS levels on V79 cells for 1-24 h. Both herbicides significantly induced the DNA damage and showed genotoxicity on lymphocytes and V79 cells. Micronucleus frequency increased significantly after pendimethalin and trifluralin treatment of the lymphocytes and V79 cells. Therefore, we concluded that both of the herbicides induced the genotoxicity through the activation of oxidative stress pathway and chromosomal damage.

Protective Effects of Ursolic Acid in the Kidneys of Diabetic Rats.

OBJECTIVES: Diabetes, a heteregenous metabolic and chronic disease, is a growing health problem in most countries. It has been claimed that diabetes is associated with the increased formation of free radicals and decreased in antioxidant potential. Oxidative stress formed in diabetes may cause DNA damage in the tissues. Ursolic acid, a well-known pentacylic triterpene, is commonly used in traditional Chinese medicine due to its beneficial health effects such as antioxidant, anticancer, and antiulcer properties. The aim of this study was to investigate the effects of ursolic acid in the kidneys of Wistar albino rats with streptozotocin-induced diabetes. MATERIALS AND METHODS: DNA damage was evaluated in the kidney cells of rats using alkaline comet assays. Oxidative stress parameters such as CAT, SOD, GR, and GSH-Px enzyme activities and total GSH and MDA levels were also evaluated. RESULTS: Ursolic acid treatment was found to significantly decrease DNA damage, GR enzyme activities, and MDA levels, and significantly increase GSH levels and CAT, SOD and GSH-Px enzyme activities in diabetic rats. CONCLUSION: According to our results, it seems that ursolic acid may be beneficial against diabetes-induced renal damage.

Impact of selenium status on Aroclor 1254-induced DNA damage in sperm and different tissues of rats.

Aroclor 1254 is a commercial mixture of polychlorinated biphenyls (PCBs), which are widespread environmental pollutants. It is used as non-flammable heat transfer agent and plasticizer. Animal studies have reported that Aroclor 1254 exerted toxic effects in different organs and systems. Although the evidences are limited, it seems reasonable that Aroclor 1254 may have a potential for similar adverse effects in humans. Selenium (Se) is a trace element and an important component of cellular antioxidant defense. This study was designed to investigate the effects of different Se status on the genotoxicity of Aroclor 1254 in sperm and different organs of Sprague-Dawley rats using Comet assay. Se deficiency (SeD) was generated by feeding 3-week old Sprague-Dawley rats with <0.05 Se mg/kg diet for 5 weeks. Se supplementation groups (SeS) were fed with 1 mg Se/kg diet. Aroclor 1254-treated rats received 10 mg/kg dose by gavage during the last 15 d of feeding period. SeD increased DNA damage in all of the organs as well as in lymphocytes and sperm. Aroclor 1254 treatment caused pronounced changes in liver, kidney and brain cells along with marked increases in lymphocytes and sperm. Se supplementation provided full or partial protection decreases in Aroclor 1254-induced DNA damage in sperm and all of tissues. Se deficiency aggravated the toxicity by increasing DNA damage caused by Aroclor 1254. Further studies should be performed to clarify the mechanism(s) underlying the protective role of Se status against Aroclor 1254 genotoxicity.

d-limonene ameliorates diabetes and its complications in streptozotocin-induced diabetic rats.

It is known that diabetes causes some complications including alterations in lipid profile, hepatic enzyme levels but also it causes oxidative stress. Limonene, a major component of Citrus oils, has important health beneficial effects in lowering the level of oxidative stress due to its antioxidant activity. The aim of this study was to investigate the effects of D-limonene on streptozotocin (STZ)-induced diabetes in Wistar albino rats. For this purpose, DNA damage was evaluated by alkaline comet assay. Changes in the activities of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSHPx) and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), total glutathione (GSH), malondialdehyde (MDA), insulin, total bilirubin and BCA protein, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol and triglyceride were also evaluated. D-limonene treatment was found to significantly decrease DNA damage, GR enzyme activities and MDA levels and significantly increase GSH levels and CAT, SOD and GSH-Px enzyme activities and altered lipid and liver enzyme parameters in diabetic rats. According to our results, it seems that D-limonene might have a role in the prevention of the complication of diabetes in rats.

Are all phytochemicals useful in the preventing of DNA damage?

Phytochemicals derived from natural plants have been used commonly for the prevention and/or treatment of different diseases due to the belief of their safety. Many plant species synthesize toxic chemicals. New natural chemicals are being discovered but their toxic effects are unknown. Phytochemicals have been regarded as possible antioxidants. But on the other hand it is suggested that various phenolic antioxidants can display pro-oxidant properties at high doses. In this review, the role of some phytochemicals (epigallocathecin gallate, carvacrol, galangin, limonene, lycopene, naringin, puerarin, terpinene, thymol and ursolic acid) on the prevention of DNA damage will be discussed.

Antigenotoxic properties of Paliurus spina-christi Mill fruits and their active compounds.

BACKGROUND: Paliurus spina-christi Mill. (PS) fruits are widely used for different medical purposes in Turkey. Like in many medicinal herbs the studies concerning their activity, the activities of PS are also not well clarified. The aim of this study is to evaluate the antigenotoxicity of the compounds isolated and identified from the extracts of PS fruits. METHODS: The active compounds were separated, isolated, and determined by chromatographic methods and their structural elucidation was performed by Nuclear Magnetic Resonance (NMR) methods. The compounds were obtained from either ethyl acetate (EA) or n-butanol extracts. The cytotoxicities of the compounds using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the antigenotoxic activities of the compounds using the alkaline single cell gel electrophoresis techniques (comet assay) were evaluated in Chinese hamster lung fibroblast (V79) cell lines. RESULTS: The isolated major compounds were identified as (+/-) catechins and gallocatechin from EA fraction and rutin from n-butanol fraction of PS fruits. Their chemical structures were identified by 1H-NMR, 13C-NMR, HMBC, and HMQC techniques. Half-maximal inhibitory concentration of catechins, gallocatechin, and rutin were found to be 734 µg/mL, 220 µg/mL, and 1004 µg/mL, respectively. The methanolic extract of PS (1-100 µg/mL) alone did not induce DNA single-strand breaks while catechins (1-100 µg/mL), gallocatechin (1-50 µg/mL), and rutin (1-50 µg/mL) significantly reduced H2O2-induced DNA damage. CONCLUSION: It has been suggested that PS fruits and their compounds catechins, gallocatechin and rutin may have beneficial effects in oxidative DNA damage. It seems that PS fruits may be used in protection of the disorders related to DNA damage.

Use of in vitro assays to assess the potential cytotoxic, genotoxic and antigenotoxic effects of vanillic and cinnamic acid.

Vanillic acid (VA) found in vanilla and cinnamic acid (CA) the precursor of flavonoids and found in cinnamon oil, are natural plant phenolic acids which are secondary aromatic plant products suggested to possess many physiological and pharmacological functions. In vitro and in vivo experiments have shown that phenolic acids exhibit powerful effects on biological responses by scavenging free radicals and eliciting antioxidant capacity. In the present study, we investigated the antioxidant capacity of VA and CA by the trolox equivalent antioxidant capacity (TEAC) assay, cytotoxicity by neutral red uptake (NRU) assay in Chinese Hamster Ovary (CHO) cells and also the genotoxic and antigenotoxic effects of these phenolic acids using the cytokinesis-blocked micronucleus (CBMN) and the alkaline comet assays in human peripheral blood lymphocytes. At all tested concentrations, VA (0.17-67.2 µg/ml) showed antioxidant activity but CA (0.15-59.2 µg/ml) did not show antioxidant activity against 2,2-azino-bis (3-ethylbenz-thiazoline-6-sulphonic acid) (ABTS). VA (0.84, 4.2, 8.4, 16.8, 84 and 168 µg/ml) and CA (0.74, 3.7, 7.4, 14.8, 74, 148 µg/ml) did not have cytotoxic and genotoxic effects alone at the studied concentrations as compared with the controls. Both VA and CA seem to decrease DNA damage induced by H2O2 in human lymphocytes.

Assessment of Genotoxic Effects of Pendimethalin in Chinese Hamster Over Cells by the Single Cell Gel Electrophoresis (Comet) Assay.

OBJECTIVES: Pendimethalin (N-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzeneamine) is a dinitroaniline herbicide compound which selectively controls weeds. It is a cell division and growth inhibitor. It descends plants in a short time after seedling. It is a soil and water pollutant due to the widespread use of formulations in Turkey and around the world. Pendimethalin is manufactured in and imported by Turkey. Pendimethalin is a slightly toxic compound that is classified in toxicity class 3 by the United States Environmental Protection Agency (USEPA). Even though it is classified as group C (human possible carcinogen) compound by the USEPA, there are limited number of studies about its genotoxic effects. The aim of this study was to evaluate in vitro genotoxic effects of different concentrations of pendimethalin in Chinese hamster over (CHO) cells by the single cell gel electrophoresis (comet) assay. MATERIALS AND METHODS: The cells are incubated with 1, 10, 100, 1000 and 10000 µM concentrations of pendimethalin for 30 min at 37°C and DNA damage was compared with CHO cells untreated with pendimethalin. 50 µM hydrogen peroxide was used as positive control. RESULTS: No significant cytotoxic effects were observed within the concentration ranges studied. The DNA damage in CHO cells was significantly increased in the pendimethalin concentrations of 1, 100, 1000 and 10000 µM, however, a significant decrease was observed in 10 µM pendimethalin concentration. CONCLUSION: Our results show that 1-10000 µM concentrations of pendimethalin induce DNA damage in CHO cells, which was assessed by comet assay.

The Ameliorative Effects of Pycnogenol® on Liver Ischemia-Reperfusion Injury in Rats.

OBJECTIVES: Pycnogenol® (PYC®), a standardized extract from the bark of Pinus maritima, consists of different phenolic compounds. PYC® has shown to have protective effects on chronic diseases such as diabetes, asthma, cancer, and immune disorders. The aim of this study was to determine the effects of PYC® against the DNA damage and biochemical changes in blood, liver, and lung tissues of ischemia-reperfusion (IR)-induced Wistar albino rats. MATERIALS AND METHODS: A sham group, IR injury-induced group, and IR+PYC® group were formed. Ischemia was induced and sustained for 45 min, then the ischemic liver was reperfused, which was sustained for a further 120 min at the end of this period. After anesthesia and before the IR inducement, 100 mg/kg PYC® was given to the IR+PYC® group through intraperitoneal injections. The total oxidant (TOS) and total antioxidant status (TAS), total thiol levels (TTL), advanced oxidation protein products (AOPP), and biochemical parameters [myeloperoxidase (MPO), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH)] in the rats were analyzed using spectrophotometric methods and DNA damage was assessed using single-cell gel electrophoresis. RESULTS: The levels of TOS, TTL, MPO, AOPP, ALT, AST, and LDH were significantly decreased in the IR+PYC® group compared with the IR group (p<0.05). The levels of TAS were significantly increased in the IR+PYC® group compared with the IR group (p<0.05). PYC® reduced the DNA damage when compared with the IR group (p<0.05). CONCLUSION: The present results suggest that PYC® treatment might have a role in the prevention of IR-induced oxidative damage by decreasing DNA damage and increasing antioxidant status.

Resveratrol Protects Sepsis-Induced Oxidative DNA Damage in Liver and Kidney of Rats.

BACKGROUND: The increases of free radicals have been proposed to be involved in the pathogenesis of sepsis, which leads to multiple-organ dysfunction syndromes. The uses of antioxidants as a complementary tool in the medical care of oxidative stress-related diseases have attracted attention of researchers. Resveratrol (RV) has suggested being antioxidant, anti-proliferative, and anti-inflammatory effects in various experimental models and clinical settings. AIMS: This study was undertaken to evaluate the protective effects of RV on oxidative DNA damage induced by sepsis in the liver and kidney tissues of Wistar albino rats. STUDY DESIGN: Animal experimentation. METHODS: Four experimental groups consisting of eight animals for each was created using a total of thirty-two male Wistar albino rats. Sham group was given 0.5 mL of saline intra-peritoneal (ip) only following laparatomy. Sepsis group was given 0.5 mL saline ip only following the induction of sepsis. RV-treated group was given a dose of 100 mg/kg ip RV in 0.5 mL saline following laparatomy. RV-treated sepsis group was given 100 mg/kg ip RV in 0.5 mL saline following the induction of sepsis. A model of sepsis was created by cecal ligation and puncture technique. In the liver and kidney tissues, oxidative stress parameters (malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX)) and a proinflammatory cytokine (tumor necrosis factor alpha (TNF-alpha)), were evaluated spectrophotometrically and DNA damage was determined by the alkaline single cell gel electrophoresis (comet assay) technique using formamidopyrimidine DNA glycosylase protein. RESULTS: In the RV-treated sepsis group, the levels of MDA and TNF-alpha were lower and GSH levels, SOD and GPX activities were higher than in the septic rats (p<0.05). RV treatment significantly reduced the sepsis-induced oxidative DNA damage in the liver and kidney cells (p<0.05). CONCLUSION: It is suggested that RV treatment might reduce the sepsis-induced oxidative DNA damages in sepsis-related diseases; however, there is a need for more studies to clear up the protective mechanisms of RV against sepsis.

MCM3AP and POMP Mutations Cause a DNA-Repair and DNA-Damage-Signaling Defect in an Immunodeficient Child.

Immunodeficiency patients with DNA repair defects exhibit radiosensitivity and proneness to leukemia/lymphoma formation. Though progress has been made in identifying the underlying mutations, in most patients the genetic basis is unknown. Two de novo mutated candidate genes, MCM3AP encoding germinal center-associated nuclear protein (GANP) and POMP encoding proteasome maturation protein (POMP), were identified by whole-exome sequencing (WES) and confirmed by Sanger sequencing in a child with complex phenotype displaying immunodeficiency, genomic instability, skin changes, and myelodysplasia. GANP was previously described to promote B-cell maturation by nuclear targeting of activation-induced cytidine deaminase (AID) and to control AID-dependent hyperrecombination. POMP is required for 20S proteasome assembly and, thus, for efficient NF-κB signaling. Patient-derived cells were characterized by impaired homologous recombination, moderate radio- and cross-linker sensitivity associated with accumulation of damage, impaired DNA damage-induced NF-κB signaling, and reduced nuclear AID levels. Complementation by wild-type (WT)-GANP normalized DNA repair and WT-POMP rescued defective NF-κB signaling. In conclusion, we identified for the first time mutations in MCM3AP and POMP in an immunodeficiency patient. These mutations lead to cooperative effects on DNA recombination and damage signaling. Digenic/polygenic mutations may constitute a novel genetic basis in immunodeficiency patients with DNA repair defects.