Hande Gürer-Orhan | Ege University (original) (raw)

Papers by Hande Gürer-Orhan

Ankara Üniversitesi Eğitim Bilimleri Fakültesi Dergisi, 2013

Kimyasal maddelerin güvenli kullanımı ile ilgili toplumda genel bilgi eksikliği olması, özellikle... more Kimyasal maddelerin güvenli kullanımı ile ilgili toplumda genel bilgi eksikliği olması, özellikle çocukları kimyasal maddeler konusunda bilinçlendirmenin gerekliliğini ortaya koymaktadır. Bu amaçla Avrupa Birliği Yaşam boyu Öğrenme Programı Leonardo da Vinci (LdV) Ortaklık Projeleri kapsamında "Đç ve dış ortam kimyasal maddelerin zararları konusunda çocukların farkındalıklarını arttırmak" adlı bir proje hazırlanmıştır. Proje için üç ülkedeki (Türkiye, Polonya, Đsveç) sekiz kurumdan oluşan disiplinler arası bir ekip oluşturulmuştur. Hazırlanacak eğitim materyalinin temel kavramlar, evimizdeki ilaçlar, ev içi temizlik ürünleri, pestisitler, plastikler, çevresel sigara dumanı ve karbonmonoksit başlıklarını içermesi planlanmış ve DVD ile öğretmenlere yönelik bir el kitabı hazırlanmıştır. Çalışmada ilköğretim 4. ve 5. sınıfa devam eden yaşları yaklaşık 10-12 arasında olan çocuklardan oluşan iki deney ve iki kontrol grubu yer almıştır. Araştırma sonucunda, ele alınan kimyasallar...

Meme kanseri, dunyada gorulme sikligi hizla artan ve kadinlarda kanserden olum nedenleri arasinda... more Meme kanseri, dunyada gorulme sikligi hizla artan ve kadinlarda kanserden olum nedenleri arasinda ikinci sirada yer alan bir kanser turudur. Endojen ostrojenlerin ve bazi eksojen ostrojenik bilesiklerin reseptor araciligiyla hucre proliferasyonunu arttirarak, ya da metabolizmalari sonucu olusan reaktif kinon metabolitlerinin DNA’ya baglanmasi ile meme kanserinin olusum ve gelisimine katkida bulundugu bildirilmektedir. Hormon bagimli meme kanserinin adjuvan tedavisinde ostrojenin etkisini ortadan kaldirmayi amaclayan mekanizmalar araciligi ile iki temel terapotik ajan grubu kullanilmaktadir; ostrojenin reseptoru araciligiyla gerceklesen etkilerini hedef alan selektif ostrojen reseptor modulatorleri (SERM) ve ostrojen sentezinde yer alan enzimatik yolaklari hedef alan selektif ostrojen enzim modulatorleri (SEEM). Bu ilaclarin cesitli yan etkilerinin olmasi ve tedavi sirasinda bazi ilaclara direnc gelismesi gibi faktorler meme kanseri tedavisinde yeni ajanlarin gelistirilmesi konusunda...

Molecules, 2021

Oxidative stress is defined as a disturbance in the prooxidant/antioxidant balance in favor of th... more Oxidative stress is defined as a disturbance in the prooxidant/antioxidant balance in favor of the former and a loss of control over redox signaling processes, leading to potential biomolecular damage. It is involved in the etiology of many diseases, varying from diabetes to neurodegenerative diseases and cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor and reported as one of the most important oxidative stress regulators. Due to its regulatory role in the expression of numerous cytoprotective genes involved in the antioxidant and anti-inflammatory responses, the modulation of NRF2 seems to be a promising approach in the prevention and treatment of cancer. Breast cancer is the prevalent type of tumor in women and is the leading cause of death among female cancers. Oxidative stress-related mechanisms are known to be involved in breast cancer, and therefore, NRF2 is considered to be beneficial in its prevention. However, its overactivation may lead ...

Antioxidants, 2020

Oxidative stress is represented as an imbalance between reactive oxygen species (ROS) production ... more Oxidative stress is represented as an imbalance between reactive oxygen species (ROS) production and the response of antioxidant proteins [...]

Xenobiotica; the fate of foreign compounds in biological systems, Jan 12, 2018

A causal association is reported between prolonged exposures to elevated levels of estrogen and b... more A causal association is reported between prolonged exposures to elevated levels of estrogen and breast cancer. Therefore inhibiting aromatase (CYP19A), which catalyses the conversion of androgens to estrogens, is an important approach in prevention and treatment of estrogen receptor positive (ER+) breast cancer. Melatonin, a natural indolic hormone, is reported to prevent free radical induced carcinogenesis and block local estrogen synthesis in breast tissue via aromatase inhibition. However several features of melatonin limit its therapeutic use. In the present study aromatase inhibiting potential of 2-methyl indole hydrazones are investigated, and compared with melatonin, by two in vitro models; a cell-free assay using a fluorescence substrate and a cell-based assay where cell proliferation was determined in ER + human breast cancer cells (MCF-7 BUS) in the absence of estrogen and the presence of testosterone. Aromatase inhibitory effect is also explored by molecular modelling stu...

Current medicinal chemistry, Jan 11, 2017

Latest data from International Agency for Cancer Research shows that breast cancer is the leading... more Latest data from International Agency for Cancer Research shows that breast cancer is the leading cancer site in women and is the leading cause of death among female cancers. Induction of reactive oxygen species (ROS) and oxidative stress as a consequence of impaired balance between prooxidants and antioxidants are suggested to be involved in induction and progression of breast cancer. Cancer cells are found to exhibit higher levels of ROS compared to normal cells. However increased antioxidant defence which balances the oxidative status within the cancer cells suggests that high ROS levels may prevent tumorigenesis via various mechanisms. These contradictory roles of ROS and oxidative stress in breast cancer let scientists investigate potential oxidative stress modulators as anticancer strategies. In the present review we address the mechanisms of ROS production in breast cancer cells, the role of impaired oxidative status as well as the benefits of introducing oxidative stress mod...

Bioorganic & medicinal chemistry, Jan 15, 2016

Oxidative stress has been recognized as a contributing factor in ageing and various diseases incl... more Oxidative stress has been recognized as a contributing factor in ageing and various diseases including cancer and neuropathological disorders. Indole derivatives such as the neurohormone melatonin (MLT) constitute an important class of therapeutic agent in medicinal chemistry. MLT can scavenge different reactive oxygen species and can also stimulate the synthesis of antioxidant enzymes. As a part of our ongoing studies, a series of new indole-based hydrazide/hydrazone derivatives were synthesized as MLT analogues. Their antioxidant activity was investigated in human erythrocytes by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Possible inherent cytotoxicity of the compounds was investigated in CHO-K1 cells by lactate dehydrogenase leakage test. Protection of neuronal PC12 cells against amyloid β-induced damage was examined by MTT assay and their ability in reduction of ROS generation induced by amyloid β was tested. MLT analogues having a...

Journal of enzyme inhibition and medicinal chemistry, Jan 8, 2016

Melatonin (MLT) is a well-known free-radical scavenger, involving in the prevention of cellular d... more Melatonin (MLT) is a well-known free-radical scavenger, involving in the prevention of cellular damage that can lead to cancer, ageing and a variety of neurodegenerative diseases. Research on MLT-related compounds has been required to optimise the maximum pharmaceutical activity with the lowest side effects. In our ongoing research, we have synthesized new indole-based MLT analogues as potential antioxidant agents by modifying the MLT molecule. In this study, we build on previous findings, through the synthesis, characterization and in vitro antioxidant profiling of a series of new indole-based MLT analogues which possess triazole, thiadiazole and carbothioamides on the third position on the indole ring. In vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox sensitive fluorescent probe and their radical scavenging activity was assessed via the DPPH assay. In addition, in vitro cytotoxic effects of newly synthesized compounds w...

Free Radical Biology and Medicine

The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants mig... more The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate the efficacy of lipoic acid (LA) in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed Chinese hamster ovary (CHO) cells and Fischer 344 rats. Furthermore, LA's ability to decrease lead levels in the blood and tissues of lead-treated rats was examined. LA administration resulted in a significant improvement in the thiol capacity of cells via increasing glutathione levels and reducing malondialdehyde levels in the lead-exposed cells and animals, indicating a strong antioxidant shift on lead-induced oxidative stress. Furthermore, administration of LA after lead treatment significantly decreased catalase and red blood cell glucose-6-phosphate dehydrogenase activity. In vitro administration of LA to cultures of CHO cells significantly increased cell survival, that was inhibited by lead treatment in a concentrationdependent manner. Administration of LA was not effective in decreasing blood or tissue lead levels compared to a well-known chelator, succimer, that was able to reduce them to control levels. Hence, LA seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent.

Archives of Environmental Contamination and Toxicology, 2001

Oxidative stress is proposed as a molecular mechanism in lead toxicity, which suggests that antio... more Oxidative stress is proposed as a molecular mechanism in lead toxicity, which suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate whether taurine has a beneficial effect both on Chinese hamster ovary (CHO) cells and on Fisher 344 (F344) rats following lead exposure. Therefore, oxidative stress parameters (glutathione, malondialdehyde levels, catalase, and glucose-6-phosphate dehydrogenase [G6PD] activities) of lead-exposed CHO cells and F344 rats were determined following taurine treatment. Taurine was found to be effective in (1) increasing glutathione levels that had been diminished by lead; (2) reducing malondialdehyde levels, an end-product of lipid peroxidation; (3) decreasing catalase and erythrocyte G6PD activity, which had been increased by lead exposure; and (4) improving cell survival of CHO cells. However, taurine had no effect on blood and tissue lead levels when 1.1 g/kg/day taurine was administered to F344 rats for 7 days, following 5 weeks of lead exposure (2,000 ppm lead acetate). As a result, taurine seems to be capable of fortifying cells against lead-induced oxidative attack without decreasing lead levels. Therefore, administration of taurine, accompanied by a chelating agent, might increase its effectiveness in the treatment of lead poisoning.

Toxicology Letters, 1997

6-Aminolevulinic Acid (a-ALA) is a heme precursor accumulated in lead poisoning and acute intermi... more 6-Aminolevulinic Acid (a-ALA) is a heme precursor accumulated in lead poisoning and acute intermittent porphyria. Although no single mechanism for lead toxicity has yet been defined, recent studies suggest at least some of the lead-induced damage may originate from d-ALA-induced oxidative stress. The present study was designed to test the hypothesis that a-ALA accumulation in Chinese hamster ovary (CHO) cells contributes to the cumulative oxidative challenge of lead poisoning as indicated by the oxidative stress parameters glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde equivalents (MDA), and catalase (CAT). It will also examine the possibility that this oxidative challenge can be reversed by treatment with an antioxidant such as N-acetylcysteine (NAC). First in vitro administration of B-ALA to CHO cells was found to have a concentration-dependent inhibitory effect on colony formation and cell survival. NAC administration was shown to alleviate this inhibition in CHO survival. The oxidative status of CIHO cell cultures exposed to increasing concentrations of B-ALA was then examined. Decreases in GSH levels (P < 0.05) were observed in the a-ALA-treated cultures as compared to the controls, while GSSG and MDA levels were significantly increased in d-ALA-treated cells (P < 0.05). CAT activity was not significantly affected. NAC administration concurrent with B-ALA exposure resulted in GSH and GSSG levels similar to the control levels, while :no significant improvement in MDA was observed. These results indicate a state of oxidative stress and suggest that the a-ALA-induced inhibitory effect on CHO colony formation may be due to its pro-oxidant effect. To assess whether this oxidative challenge would induce antioxidant increases during extended exposure to S-ALA, CHO cells were exposed to 5 mM d-ALA for increasing time periods. The GSH and GSSG levels were measured and a rebound effect was observed after 12 h of B-ALA exposure.

Toxicology, 1998

Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to bioc... more Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to biochemical and physiological dysfunction. The present study investigated the effects of exposure on the redox status of the lenses of Fisher 344 rats and examined whether antioxidant or chelator administration reversed these changes. Animals were given 5 weeks of 2000 ppm Pb exposure followed by 1 week of either antioxidant, chelator or distilled water administration. Glutathione (GSH) and cysteine (CYS) levels decreased in the Pb-exposed group. N-acetylcysteine or 2,3-dimercaptopsuccinic acid (Succimer) supplementation following Pb intoxication resulted in increases in the GSH and CYS levels. Protein bound glutathione (PSSG) and cysteine (PSSC) increased following Pb exposure. In the Succimer-treated animals, the PSSG decreased significantly. The glutathione disulfide (GSSG) levels remained unchanged. Malondialdehyde (MDA) levels, a major lipid peroxidation byproduct, increased following Pb exposure and decreased following Succimer treatment. Our results suggest that antioxidant supplementation, as well as chelation, following Pb exposure may enhance the reductive status of lenses.

Free Radical Biology and Medicine, 1999

Free Radical Biology and Medicine, 1998

Free Radical Biology and Medicine, 2000

Recent studies have shown that lead causes oxidative stress by inducing the generation of reactiv... more Recent studies have shown that lead causes oxidative stress by inducing the generation of reactive oxygen species, reducing the antioxidant defense system of cells via depleting glutathione, inhibiting sulfhydryl-dependent enzymes, interfering with some essential metals needed for antioxidant enzyme activities, and/or increasing susceptibility of cells to oxidative attack by altering the membrane integrity and fatty acid composition. Consequently, it is plausible that impaired oxidant/antioxidant balance can be partially responsible for the toxic effects of lead. Where enhanced oxidative stress contributes to lead-induced toxicity, restoration of a cell's antioxidant capacity appears to provide a partial remedy. Several studies are underway to determine the effect of antioxidant supplementation following lead exposure. Data suggest that antioxidants may play an important role in abating some hazards of lead. To explain the importance of using antioxidants in treating lead poisoning the following topics are addressed: (i) Oxidative damage caused by lead poisoning; (ii) conventional treatment of lead poisoning and its side effects; and (iii) possible protective effects of antioxidants in lead toxicity.

Free Radical Biology and Medicine, 1999

Lead (Pb) is known to negatively affect glutathione (GSH) metabolism in the lens. The present stu... more Lead (Pb) is known to negatively affect glutathione (GSH) metabolism in the lens. The present study examined the effects of Captopril, Taurine, and ␣-Lipoic acid on the Pb-induced GSH depletion and lipid peroxide increase in the lenticular system. Captopril administration returned the GSH, cysteine (CYS), and malondialdehyde (MDA) levels to near normal. Following Taurine administration the GSH, CYS and MDA levels were intermediate between the control group and the Pb group levels. ␣-Lipoic acid administration, however, only increased the CYS levels. No significant changes in oxidized glutathione (GSSG) levels were observed in any treatment group.

Ankara Üniversitesi Eğitim Bilimleri Fakültesi Dergisi, 2013

Kimyasal maddelerin güvenli kullanımı ile ilgili toplumda genel bilgi eksikliği olması, özellikle... more Kimyasal maddelerin güvenli kullanımı ile ilgili toplumda genel bilgi eksikliği olması, özellikle çocukları kimyasal maddeler konusunda bilinçlendirmenin gerekliliğini ortaya koymaktadır. Bu amaçla Avrupa Birliği Yaşam boyu Öğrenme Programı Leonardo da Vinci (LdV) Ortaklık Projeleri kapsamında "Đç ve dış ortam kimyasal maddelerin zararları konusunda çocukların farkındalıklarını arttırmak" adlı bir proje hazırlanmıştır. Proje için üç ülkedeki (Türkiye, Polonya, Đsveç) sekiz kurumdan oluşan disiplinler arası bir ekip oluşturulmuştur. Hazırlanacak eğitim materyalinin temel kavramlar, evimizdeki ilaçlar, ev içi temizlik ürünleri, pestisitler, plastikler, çevresel sigara dumanı ve karbonmonoksit başlıklarını içermesi planlanmış ve DVD ile öğretmenlere yönelik bir el kitabı hazırlanmıştır. Çalışmada ilköğretim 4. ve 5. sınıfa devam eden yaşları yaklaşık 10-12 arasında olan çocuklardan oluşan iki deney ve iki kontrol grubu yer almıştır. Araştırma sonucunda, ele alınan kimyasallar...

Meme kanseri, dunyada gorulme sikligi hizla artan ve kadinlarda kanserden olum nedenleri arasinda... more Meme kanseri, dunyada gorulme sikligi hizla artan ve kadinlarda kanserden olum nedenleri arasinda ikinci sirada yer alan bir kanser turudur. Endojen ostrojenlerin ve bazi eksojen ostrojenik bilesiklerin reseptor araciligiyla hucre proliferasyonunu arttirarak, ya da metabolizmalari sonucu olusan reaktif kinon metabolitlerinin DNA’ya baglanmasi ile meme kanserinin olusum ve gelisimine katkida bulundugu bildirilmektedir. Hormon bagimli meme kanserinin adjuvan tedavisinde ostrojenin etkisini ortadan kaldirmayi amaclayan mekanizmalar araciligi ile iki temel terapotik ajan grubu kullanilmaktadir; ostrojenin reseptoru araciligiyla gerceklesen etkilerini hedef alan selektif ostrojen reseptor modulatorleri (SERM) ve ostrojen sentezinde yer alan enzimatik yolaklari hedef alan selektif ostrojen enzim modulatorleri (SEEM). Bu ilaclarin cesitli yan etkilerinin olmasi ve tedavi sirasinda bazi ilaclara direnc gelismesi gibi faktorler meme kanseri tedavisinde yeni ajanlarin gelistirilmesi konusunda...

Molecules, 2021

Oxidative stress is defined as a disturbance in the prooxidant/antioxidant balance in favor of th... more Oxidative stress is defined as a disturbance in the prooxidant/antioxidant balance in favor of the former and a loss of control over redox signaling processes, leading to potential biomolecular damage. It is involved in the etiology of many diseases, varying from diabetes to neurodegenerative diseases and cancer. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor and reported as one of the most important oxidative stress regulators. Due to its regulatory role in the expression of numerous cytoprotective genes involved in the antioxidant and anti-inflammatory responses, the modulation of NRF2 seems to be a promising approach in the prevention and treatment of cancer. Breast cancer is the prevalent type of tumor in women and is the leading cause of death among female cancers. Oxidative stress-related mechanisms are known to be involved in breast cancer, and therefore, NRF2 is considered to be beneficial in its prevention. However, its overactivation may lead ...

Antioxidants, 2020

Oxidative stress is represented as an imbalance between reactive oxygen species (ROS) production ... more Oxidative stress is represented as an imbalance between reactive oxygen species (ROS) production and the response of antioxidant proteins [...]

Xenobiotica; the fate of foreign compounds in biological systems, Jan 12, 2018

A causal association is reported between prolonged exposures to elevated levels of estrogen and b... more A causal association is reported between prolonged exposures to elevated levels of estrogen and breast cancer. Therefore inhibiting aromatase (CYP19A), which catalyses the conversion of androgens to estrogens, is an important approach in prevention and treatment of estrogen receptor positive (ER+) breast cancer. Melatonin, a natural indolic hormone, is reported to prevent free radical induced carcinogenesis and block local estrogen synthesis in breast tissue via aromatase inhibition. However several features of melatonin limit its therapeutic use. In the present study aromatase inhibiting potential of 2-methyl indole hydrazones are investigated, and compared with melatonin, by two in vitro models; a cell-free assay using a fluorescence substrate and a cell-based assay where cell proliferation was determined in ER + human breast cancer cells (MCF-7 BUS) in the absence of estrogen and the presence of testosterone. Aromatase inhibitory effect is also explored by molecular modelling stu...

Current medicinal chemistry, Jan 11, 2017

Latest data from International Agency for Cancer Research shows that breast cancer is the leading... more Latest data from International Agency for Cancer Research shows that breast cancer is the leading cancer site in women and is the leading cause of death among female cancers. Induction of reactive oxygen species (ROS) and oxidative stress as a consequence of impaired balance between prooxidants and antioxidants are suggested to be involved in induction and progression of breast cancer. Cancer cells are found to exhibit higher levels of ROS compared to normal cells. However increased antioxidant defence which balances the oxidative status within the cancer cells suggests that high ROS levels may prevent tumorigenesis via various mechanisms. These contradictory roles of ROS and oxidative stress in breast cancer let scientists investigate potential oxidative stress modulators as anticancer strategies. In the present review we address the mechanisms of ROS production in breast cancer cells, the role of impaired oxidative status as well as the benefits of introducing oxidative stress mod...

Bioorganic & medicinal chemistry, Jan 15, 2016

Oxidative stress has been recognized as a contributing factor in ageing and various diseases incl... more Oxidative stress has been recognized as a contributing factor in ageing and various diseases including cancer and neuropathological disorders. Indole derivatives such as the neurohormone melatonin (MLT) constitute an important class of therapeutic agent in medicinal chemistry. MLT can scavenge different reactive oxygen species and can also stimulate the synthesis of antioxidant enzymes. As a part of our ongoing studies, a series of new indole-based hydrazide/hydrazone derivatives were synthesized as MLT analogues. Their antioxidant activity was investigated in human erythrocytes by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Possible inherent cytotoxicity of the compounds was investigated in CHO-K1 cells by lactate dehydrogenase leakage test. Protection of neuronal PC12 cells against amyloid β-induced damage was examined by MTT assay and their ability in reduction of ROS generation induced by amyloid β was tested. MLT analogues having a...

Journal of enzyme inhibition and medicinal chemistry, Jan 8, 2016

Melatonin (MLT) is a well-known free-radical scavenger, involving in the prevention of cellular d... more Melatonin (MLT) is a well-known free-radical scavenger, involving in the prevention of cellular damage that can lead to cancer, ageing and a variety of neurodegenerative diseases. Research on MLT-related compounds has been required to optimise the maximum pharmaceutical activity with the lowest side effects. In our ongoing research, we have synthesized new indole-based MLT analogues as potential antioxidant agents by modifying the MLT molecule. In this study, we build on previous findings, through the synthesis, characterization and in vitro antioxidant profiling of a series of new indole-based MLT analogues which possess triazole, thiadiazole and carbothioamides on the third position on the indole ring. In vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox sensitive fluorescent probe and their radical scavenging activity was assessed via the DPPH assay. In addition, in vitro cytotoxic effects of newly synthesized compounds w...

Free Radical Biology and Medicine

The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants mig... more The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate the efficacy of lipoic acid (LA) in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed Chinese hamster ovary (CHO) cells and Fischer 344 rats. Furthermore, LA's ability to decrease lead levels in the blood and tissues of lead-treated rats was examined. LA administration resulted in a significant improvement in the thiol capacity of cells via increasing glutathione levels and reducing malondialdehyde levels in the lead-exposed cells and animals, indicating a strong antioxidant shift on lead-induced oxidative stress. Furthermore, administration of LA after lead treatment significantly decreased catalase and red blood cell glucose-6-phosphate dehydrogenase activity. In vitro administration of LA to cultures of CHO cells significantly increased cell survival, that was inhibited by lead treatment in a concentrationdependent manner. Administration of LA was not effective in decreasing blood or tissue lead levels compared to a well-known chelator, succimer, that was able to reduce them to control levels. Hence, LA seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent.

Archives of Environmental Contamination and Toxicology, 2001

Oxidative stress is proposed as a molecular mechanism in lead toxicity, which suggests that antio... more Oxidative stress is proposed as a molecular mechanism in lead toxicity, which suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate whether taurine has a beneficial effect both on Chinese hamster ovary (CHO) cells and on Fisher 344 (F344) rats following lead exposure. Therefore, oxidative stress parameters (glutathione, malondialdehyde levels, catalase, and glucose-6-phosphate dehydrogenase [G6PD] activities) of lead-exposed CHO cells and F344 rats were determined following taurine treatment. Taurine was found to be effective in (1) increasing glutathione levels that had been diminished by lead; (2) reducing malondialdehyde levels, an end-product of lipid peroxidation; (3) decreasing catalase and erythrocyte G6PD activity, which had been increased by lead exposure; and (4) improving cell survival of CHO cells. However, taurine had no effect on blood and tissue lead levels when 1.1 g/kg/day taurine was administered to F344 rats for 7 days, following 5 weeks of lead exposure (2,000 ppm lead acetate). As a result, taurine seems to be capable of fortifying cells against lead-induced oxidative attack without decreasing lead levels. Therefore, administration of taurine, accompanied by a chelating agent, might increase its effectiveness in the treatment of lead poisoning.

Toxicology Letters, 1997

6-Aminolevulinic Acid (a-ALA) is a heme precursor accumulated in lead poisoning and acute intermi... more 6-Aminolevulinic Acid (a-ALA) is a heme precursor accumulated in lead poisoning and acute intermittent porphyria. Although no single mechanism for lead toxicity has yet been defined, recent studies suggest at least some of the lead-induced damage may originate from d-ALA-induced oxidative stress. The present study was designed to test the hypothesis that a-ALA accumulation in Chinese hamster ovary (CHO) cells contributes to the cumulative oxidative challenge of lead poisoning as indicated by the oxidative stress parameters glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde equivalents (MDA), and catalase (CAT). It will also examine the possibility that this oxidative challenge can be reversed by treatment with an antioxidant such as N-acetylcysteine (NAC). First in vitro administration of B-ALA to CHO cells was found to have a concentration-dependent inhibitory effect on colony formation and cell survival. NAC administration was shown to alleviate this inhibition in CHO survival. The oxidative status of CIHO cell cultures exposed to increasing concentrations of B-ALA was then examined. Decreases in GSH levels (P < 0.05) were observed in the a-ALA-treated cultures as compared to the controls, while GSSG and MDA levels were significantly increased in d-ALA-treated cells (P < 0.05). CAT activity was not significantly affected. NAC administration concurrent with B-ALA exposure resulted in GSH and GSSG levels similar to the control levels, while :no significant improvement in MDA was observed. These results indicate a state of oxidative stress and suggest that the a-ALA-induced inhibitory effect on CHO colony formation may be due to its pro-oxidant effect. To assess whether this oxidative challenge would induce antioxidant increases during extended exposure to S-ALA, CHO cells were exposed to 5 mM d-ALA for increasing time periods. The GSH and GSSG levels were measured and a rebound effect was observed after 12 h of B-ALA exposure.

Toxicology, 1998

Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to bioc... more Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to biochemical and physiological dysfunction. The present study investigated the effects of exposure on the redox status of the lenses of Fisher 344 rats and examined whether antioxidant or chelator administration reversed these changes. Animals were given 5 weeks of 2000 ppm Pb exposure followed by 1 week of either antioxidant, chelator or distilled water administration. Glutathione (GSH) and cysteine (CYS) levels decreased in the Pb-exposed group. N-acetylcysteine or 2,3-dimercaptopsuccinic acid (Succimer) supplementation following Pb intoxication resulted in increases in the GSH and CYS levels. Protein bound glutathione (PSSG) and cysteine (PSSC) increased following Pb exposure. In the Succimer-treated animals, the PSSG decreased significantly. The glutathione disulfide (GSSG) levels remained unchanged. Malondialdehyde (MDA) levels, a major lipid peroxidation byproduct, increased following Pb exposure and decreased following Succimer treatment. Our results suggest that antioxidant supplementation, as well as chelation, following Pb exposure may enhance the reductive status of lenses.

Free Radical Biology and Medicine, 1999

Free Radical Biology and Medicine, 1998

Free Radical Biology and Medicine, 2000

Recent studies have shown that lead causes oxidative stress by inducing the generation of reactiv... more Recent studies have shown that lead causes oxidative stress by inducing the generation of reactive oxygen species, reducing the antioxidant defense system of cells via depleting glutathione, inhibiting sulfhydryl-dependent enzymes, interfering with some essential metals needed for antioxidant enzyme activities, and/or increasing susceptibility of cells to oxidative attack by altering the membrane integrity and fatty acid composition. Consequently, it is plausible that impaired oxidant/antioxidant balance can be partially responsible for the toxic effects of lead. Where enhanced oxidative stress contributes to lead-induced toxicity, restoration of a cell's antioxidant capacity appears to provide a partial remedy. Several studies are underway to determine the effect of antioxidant supplementation following lead exposure. Data suggest that antioxidants may play an important role in abating some hazards of lead. To explain the importance of using antioxidants in treating lead poisoning the following topics are addressed: (i) Oxidative damage caused by lead poisoning; (ii) conventional treatment of lead poisoning and its side effects; and (iii) possible protective effects of antioxidants in lead toxicity.

Free Radical Biology and Medicine, 1999

Lead (Pb) is known to negatively affect glutathione (GSH) metabolism in the lens. The present stu... more Lead (Pb) is known to negatively affect glutathione (GSH) metabolism in the lens. The present study examined the effects of Captopril, Taurine, and ␣-Lipoic acid on the Pb-induced GSH depletion and lipid peroxide increase in the lenticular system. Captopril administration returned the GSH, cysteine (CYS), and malondialdehyde (MDA) levels to near normal. Following Taurine administration the GSH, CYS and MDA levels were intermediate between the control group and the Pb group levels. ␣-Lipoic acid administration, however, only increased the CYS levels. No significant changes in oxidized glutathione (GSSG) levels were observed in any treatment group.

Ege Üniversitesi Basımevi, 2019

Bu el kitabı, Prof. Dr. Hatice ŞAHİN, Prof. Dr. Hülya ÜÇERLER, Prof. Dr. Ferhan SAĞIN, Prof. Dr. ... more Bu el kitabı, Prof. Dr. Hatice ŞAHİN, Prof. Dr. Hülya ÜÇERLER, Prof. Dr. Ferhan SAĞIN, Prof. Dr. Aynur UYSAL TORAMAN, Prof. Dr. Timuçin GENÇER, Prof. Dr. Mine HOŞGÖR LİMONCU, Prof. Dr. Hande GÜRER ORHAN, Prof. Dr. Nurcan BUDUNELİ, Doç. Dr. Yasemin ERAÇ, Öğr. Gör. Ozan KARACA ve Seher BAYGIN DAŞIKAN tarafından öğretim üyeleri ve öğrencilere lisansüstü eğitimde danışmanlık süreçlerinde rehberlik etmesi amacıyla hazırlanmıştır.