Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016013997
Venkatesan Kathiresan, S. Subburaman, A. V. Krishna, M. Natarajan, Gandhidasan Rathinasamy, Kumaresan Ganesan, M. Ramachandran
Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2.5 mg/kg) treated, and DOX (2.5 mg/kg) + NAR (50 mg/kg/d) treated. DOX administration significantly altered the levels of functional markers in blood and antioxidant enzymes in kidney, heart, lung, liver, spleen, and tumor tissues. These changes in antioxidant enzymes and successive lipid peroxidation were prevented by NAR supplementation, resulting in decreases in the risk of toxicity due to DOX therapy. Histopathology results and electron paramagnetic resonance imaging (EPRI) of the tumor microenvironment confirmed this evidence. Using EPRI, pharmacokinetics of the nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3-CP) was monitored intratumorally before and after chemotherapy. EPRI of the DOX + NAR-treated mouse model showed reduced tumor size with significant modification of the hypoxic condition inside the tumor microenvironment. Consequently, these findings suggest that NAR treatment significantly reduces DOX-induced toxicity and the hypoxic condition in a DLA tumor-bearing mouse model.
{"title":"Naringenin Ameliorates Doxorubicin Toxicity and Hypoxic Condition in Dalton's Lymphoma Ascites Tumor Mouse Model: Evidence from Electron Paramagnetic Resonance Imaging.","authors":"Venkatesan Kathiresan, S. Subburaman, A. V. Krishna, M. Natarajan, Gandhidasan Rathinasamy, Kumaresan Ganesan, M. Ramachandran","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016013997","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016013997","url":null,"abstract":"Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2.5 mg/kg) treated, and DOX (2.5 mg/kg) + NAR (50 mg/kg/d) treated. DOX administration significantly altered the levels of functional markers in blood and antioxidant enzymes in kidney, heart, lung, liver, spleen, and tumor tissues. These changes in antioxidant enzymes and successive lipid peroxidation were prevented by NAR supplementation, resulting in decreases in the risk of toxicity due to DOX therapy. Histopathology results and electron paramagnetic resonance imaging (EPRI) of the tumor microenvironment confirmed this evidence. Using EPRI, pharmacokinetics of the nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3-CP) was monitored intratumorally before and after chemotherapy. EPRI of the DOX + NAR-treated mouse model showed reduced tumor size with significant modification of the hypoxic condition inside the tumor microenvironment. Consequently, these findings suggest that NAR treatment significantly reduces DOX-induced toxicity and the hypoxic condition in a DLA tumor-bearing mouse model.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"67 1","pages":"249-262"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86975340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016014030
M. Kujawska, Patrycja Kant, I. H. Mayoral, E. Ignatowicz, J. Sikora, J. Oszmiański, J. Czapski, J. Jodynis-Liebert
Because humans commonly consume chokeberry, especially as a nutritional supplement, it must be checked to determine whether its excessive ingestion can cause adverse effects, in particular, in the case of simultaneous exposure to some xenobiotics. From this point of view, we examined the impact of long-term cotreatment of rats with chokeberry juice and hepatic carcinogen N-nitrosodiethylamine (NDEA) on oxidative damages and neoplastic lesions in the liver of rats. Daily exposure to chokeberry juice in a concentration of 10 g/kg feed via diet for 13 wk led to an intensified hepatotoxic effect of NDEA (0.01% in drinking water for 13 wk), as evidenced by changes in histopathological architecture of liver tissue, increased lipid peroxidation, protein carbonyl formation, and DNA degradation. Moreover, we noticed an increase in relative liver weight and a decrease in body weight in this group in comparison to NDEA-alone treated animals. Chokeberry juice applied alone did not cause any adverse effects in rats. On the basis of these findings, it can be concluded that high doses and longterm administration of chokeberry juice may enhance tumor-promoting action of some chemical carcinogens.
{"title":"Effect of Chokeberry Juice on N-Nitrosodiethylamine-Induced Rat Liver Carcinogenesis.","authors":"M. Kujawska, Patrycja Kant, I. H. Mayoral, E. Ignatowicz, J. Sikora, J. Oszmiański, J. Czapski, J. Jodynis-Liebert","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016014030","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016014030","url":null,"abstract":"Because humans commonly consume chokeberry, especially as a nutritional supplement, it must be checked to determine whether its excessive ingestion can cause adverse effects, in particular, in the case of simultaneous exposure to some xenobiotics. From this point of view, we examined the impact of long-term cotreatment of rats with chokeberry juice and hepatic carcinogen N-nitrosodiethylamine (NDEA) on oxidative damages and neoplastic lesions in the liver of rats. Daily exposure to chokeberry juice in a concentration of 10 g/kg feed via diet for 13 wk led to an intensified hepatotoxic effect of NDEA (0.01% in drinking water for 13 wk), as evidenced by changes in histopathological architecture of liver tissue, increased lipid peroxidation, protein carbonyl formation, and DNA degradation. Moreover, we noticed an increase in relative liver weight and a decrease in body weight in this group in comparison to NDEA-alone treated animals. Chokeberry juice applied alone did not cause any adverse effects in rats. On the basis of these findings, it can be concluded that high doses and longterm administration of chokeberry juice may enhance tumor-promoting action of some chemical carcinogens.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"96 1","pages":"317-331"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88408001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016015704
Preety Ghanghas, Shelly Jain, Chandan Rana, S. Sanyal
Cancer cells require nourishment for the growth of the primary tumor mass and spread of the metastatic colony. These needs are fulfilled by tumor-associated neovasculature known as angiogenesis, which also favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore, targeting angiogenesis is profitable as a mechanism to inhibit tumor growth. Furthermore, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in the neoplastic and proinflammatory milieu. We studied the role of two important chemokines (monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [MIP-1β]) along with VEGF and MMPs in nonsteroidal anti-inflammatory drug (NSAID)-induced chemopreventive effects in experimental colon cancer in rats. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used as cancer-inducing agent and three NSAIDs (celecoxib, etoricoxib, and diclofenac) were given orally as chemopreventive agents. Analysis by immunofluorescence and western blotting shows that the expression of VEGF, MMP-2, and MMP-9 was found to be significantly elevated in the DMH- treated group and notably lowered by NSAID coadministration. The expression of MCP-1 was found to be markedly decreased, whereas that of MIP-1β increased after NSAID coadministration. NSAID coadministration was also able to induce apoptosis, confirmed using studies by Hoechst/propidium iodide (PI) costaining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results from the present study indicate the potential role of these chemokines along with VEGF and MMPs against angiogenesis in DMH-induced cancer. The inhibition of angiogenesis and induction of apoptosis by NSAIDs were found to be possible mechanisms in the chemoprevention of colon cancer.
{"title":"Chemoprevention of Colon Cancer through Inhibition of Angiogenesis and Induction of Apoptosis by Nonsteroidal Anti-Inflammatory Drugs.","authors":"Preety Ghanghas, Shelly Jain, Chandan Rana, S. Sanyal","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016015704","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016015704","url":null,"abstract":"Cancer cells require nourishment for the growth of the primary tumor mass and spread of the metastatic colony. These needs are fulfilled by tumor-associated neovasculature known as angiogenesis, which also favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore, targeting angiogenesis is profitable as a mechanism to inhibit tumor growth. Furthermore, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in the neoplastic and proinflammatory milieu. We studied the role of two important chemokines (monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [MIP-1β]) along with VEGF and MMPs in nonsteroidal anti-inflammatory drug (NSAID)-induced chemopreventive effects in experimental colon cancer in rats. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used as cancer-inducing agent and three NSAIDs (celecoxib, etoricoxib, and diclofenac) were given orally as chemopreventive agents. Analysis by immunofluorescence and western blotting shows that the expression of VEGF, MMP-2, and MMP-9 was found to be significantly elevated in the DMH- treated group and notably lowered by NSAID coadministration. The expression of MCP-1 was found to be markedly decreased, whereas that of MIP-1β increased after NSAID coadministration. NSAID coadministration was also able to induce apoptosis, confirmed using studies by Hoechst/propidium iodide (PI) costaining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results from the present study indicate the potential role of these chemokines along with VEGF and MMPs against angiogenesis in DMH-induced cancer. The inhibition of angiogenesis and induction of apoptosis by NSAIDs were found to be possible mechanisms in the chemoprevention of colon cancer.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"60 1","pages":"273-289"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79109345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016379
M. Matysiak, M. Kruszewski, B. Jodłowska-Jędrych, L. Kapka-Skrzypczak
The aim of this study was to summarize the current state of knowledge on pesticide-related fertility problems and disadventeges of childrens due to prenatal pesticides exposure. Available literature was analyzed. Due to the extent of the issue, the study focuses on epidemiological studies conducted in humans, despite evidence from in vitro and animal studies. It seems certain that exposure to harmful chemicals is one of the factors that may cause a decline in fertility and problems with conceiving, whereas exposure during pregnancy can impair foetal development. Prenatal exposure may also result in the occurrence of childhood cancer and neurobehavioral disorders. The meaning of the project is to summarize the role of pesticides in the process of reproduction. This applies especially to people working in agriculture, since they might be occupationally exposed to pesticides.
{"title":"Effect of Prenatal Exposure to Pesticides on Children's Health.","authors":"M. Matysiak, M. Kruszewski, B. Jodłowska-Jędrych, L. Kapka-Skrzypczak","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016379","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016379","url":null,"abstract":"The aim of this study was to summarize the current state of knowledge on pesticide-related fertility problems and disadventeges of childrens due to prenatal pesticides exposure. Available literature was analyzed. Due to the extent of the issue, the study focuses on epidemiological studies conducted in humans, despite evidence from in vitro and animal studies. It seems certain that exposure to harmful chemicals is one of the factors that may cause a decline in fertility and problems with conceiving, whereas exposure during pregnancy can impair foetal development. Prenatal exposure may also result in the occurrence of childhood cancer and neurobehavioral disorders. The meaning of the project is to summarize the role of pesticides in the process of reproduction. This applies especially to people working in agriculture, since they might be occupationally exposed to pesticides.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"69 1","pages":"375-386"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90745452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016184
M. Yazdani, K. Hylland
The kinetics of reactive oxygen species (ROS) formation in a primary culture of rainbow trout hepatocytes was investigated using three fluorescent probes: 5-,6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA), dihydrorhodamine 123 (DHR 123), and dihydroethidium (DHE). The cell cultures were loaded with the three probes, separately. Hepatocytes were then exposed to Cu (0.15-10 mM) in serum-free Leibovitz's medium for 30 min before being quantified by a fluorescence plate reader during 30 min. Membrane integrity and glutathione (GSH) content were quantified using the fluorescent probes 5-carboxyfluorescein diacetate-acetoxymethyl ester (CFDA-AM) and monochlorobimane. Increasing ROS formation with increasing concentrations of Cu was shown using CM-H2DCFDA, whereas DHR 123 fluorescence decreased. Significant differences between control and treatment groups were observed at the highest concentrations (2.5 and 10 mM) for both probes. DHE fluorescence was lower than that of the other two probes and did not appear to be affected by any exposure. Additionally, a dose-dependent depletion of GSH and decreasing membrane integrity with increasing Cu concentrations were demonstrated, with significant effects observed at 2.5 and 10 mM for both endpoints. The results showed that both CMH2DCFDA and DHR 123 detected the development of their target Cu-induced ROS in trout hepatocytes but did so in opposite fashions. DHE was found to be unsuitable for detecting kinetics of ROS formation in this model system.
{"title":"A Kinetic Study of Reactive Oxygen Species in Rainbow Trout Hepatocytes by Fluorometry.","authors":"M. Yazdani, K. Hylland","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016184","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2016016184","url":null,"abstract":"The kinetics of reactive oxygen species (ROS) formation in a primary culture of rainbow trout hepatocytes was investigated using three fluorescent probes: 5-,6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA), dihydrorhodamine 123 (DHR 123), and dihydroethidium (DHE). The cell cultures were loaded with the three probes, separately. Hepatocytes were then exposed to Cu (0.15-10 mM) in serum-free Leibovitz's medium for 30 min before being quantified by a fluorescence plate reader during 30 min. Membrane integrity and glutathione (GSH) content were quantified using the fluorescent probes 5-carboxyfluorescein diacetate-acetoxymethyl ester (CFDA-AM) and monochlorobimane. Increasing ROS formation with increasing concentrations of Cu was shown using CM-H2DCFDA, whereas DHR 123 fluorescence decreased. Significant differences between control and treatment groups were observed at the highest concentrations (2.5 and 10 mM) for both probes. DHE fluorescence was lower than that of the other two probes and did not appear to be affected by any exposure. Additionally, a dose-dependent depletion of GSH and decreasing membrane integrity with increasing Cu concentrations were demonstrated, with significant effects observed at 2.5 and 10 mM for both endpoints. The results showed that both CMH2DCFDA and DHR 123 detected the development of their target Cu-induced ROS in trout hepatocytes but did so in opposite fashions. DHE was found to be unsuitable for detecting kinetics of ROS formation in this model system.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"19 1","pages":"291-297"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89174658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2015014168
C. Sharma, Monika Sharma, B. Aggarwal, V. Sharma
Vitiligo is a hypopigmentation disorder that is caused by the loss of melanocyte activity for melanin pigment generation. Vitiligo is distinguished by the existence of white macules. Vitiligo affects 0.1%-2% of individuals of different populations, irrespective of skin color, ethnic origin, race, or age. Although the actual mechanism behind this disease is not yet known, it is thought to be caused by a cumulative effect of various mechanisms (e.g., neurohormonal, genetic, cytotoxic, oxidative stress, autoimmune, and biochemical). This article reviews the published literature on various treatment modalities that might be effective in successfully treating patients with vitiligo, including phototherapies or some photochemotherapies, vitamin D analogs, topical and systemic corticosteroids, zinc treatment, anti-tumor necrosis factor agents, calcineurin inhibitors (tacrolimus, pimecrolimus), and surgical methods. This critical review also discusses a few herbal medications that may be worthy of future investigation because they have no significant side effects.
{"title":"Different Advanced Therapeutic Approaches to Treat Vitiligo.","authors":"C. Sharma, Monika Sharma, B. Aggarwal, V. Sharma","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2015014168","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2015014168","url":null,"abstract":"Vitiligo is a hypopigmentation disorder that is caused by the loss of melanocyte activity for melanin pigment generation. Vitiligo is distinguished by the existence of white macules. Vitiligo affects 0.1%-2% of individuals of different populations, irrespective of skin color, ethnic origin, race, or age. Although the actual mechanism behind this disease is not yet known, it is thought to be caused by a cumulative effect of various mechanisms (e.g., neurohormonal, genetic, cytotoxic, oxidative stress, autoimmune, and biochemical). This article reviews the published literature on various treatment modalities that might be effective in successfully treating patients with vitiligo, including phototherapies or some photochemotherapies, vitamin D analogs, topical and systemic corticosteroids, zinc treatment, anti-tumor necrosis factor agents, calcineurin inhibitors (tacrolimus, pimecrolimus), and surgical methods. This critical review also discusses a few herbal medications that may be worthy of future investigation because they have no significant side effects.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"17 1","pages":"321-34"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80315173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013946
J. Joy, S. Alarifi, E. Alsuhaibani, C. Nair
This study aims to investigate whether asiaticoside, a triterpene glycoside, can afford protection to DNA from alterations induced by gamma radiation under in vitro, ex vivo, and in vivo conditions. In vitro studies were done on plasmid pBR322 DNA, ex vivo studies were done on cellular DNA of human peripheral blood leukocytes, and in vivo investigations were conducted on cellular DNA of spleen and bone marrow cells of mice exposed to whole-body gamma radiation. The supercoiled form of the plasmid pBR322 DNA upon exposure to the radiation was converted into relaxed open circular form due to induction of strand breaks. Presence of asiaticoside along with the DNA during irradiation prevented the relaxation of the supercoiled form to the open circular form. When human peripheral blood leukocytes were exposed to gamma radiation, the cellular DNA suffered strand breaks as evidenced by the increased comet parameters in an alkaline comet assay. Asiaticoside, when present along with blood during irradiation ex vivo, prevented the strand breaks and the comet parameters were closer to that of the controls. Whole-body exposure of mice to gamma radiation resulted in a significant increase in comet parameters of DNA of bone marrow and spleen cells of mice as a result of radiation-induced strand breaks in DNA. Administration of asiaticoside prior to whole-body radiation exposure of the mice prevented this increase in radiation-induced increase in comet parameters, which could be the result of protection to DNA under in vivo conditions of radiation exposure. Thus, it can be concluded from the results that asiaticoside can offer protection to DNA from radiation-induced alterations under in vitro, ex vivo, and in vivo conditions.
{"title":"Protection of DNA From Ionizing Radiation-Induced Lesions by Asiaticoside.","authors":"J. Joy, S. Alarifi, E. Alsuhaibani, C. Nair","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013946","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013946","url":null,"abstract":"This study aims to investigate whether asiaticoside, a triterpene glycoside, can afford protection to DNA from alterations induced by gamma radiation under in vitro, ex vivo, and in vivo conditions. In vitro studies were done on plasmid pBR322 DNA, ex vivo studies were done on cellular DNA of human peripheral blood leukocytes, and in vivo investigations were conducted on cellular DNA of spleen and bone marrow cells of mice exposed to whole-body gamma radiation. The supercoiled form of the plasmid pBR322 DNA upon exposure to the radiation was converted into relaxed open circular form due to induction of strand breaks. Presence of asiaticoside along with the DNA during irradiation prevented the relaxation of the supercoiled form to the open circular form. When human peripheral blood leukocytes were exposed to gamma radiation, the cellular DNA suffered strand breaks as evidenced by the increased comet parameters in an alkaline comet assay. Asiaticoside, when present along with blood during irradiation ex vivo, prevented the strand breaks and the comet parameters were closer to that of the controls. Whole-body exposure of mice to gamma radiation resulted in a significant increase in comet parameters of DNA of bone marrow and spleen cells of mice as a result of radiation-induced strand breaks in DNA. Administration of asiaticoside prior to whole-body radiation exposure of the mice prevented this increase in radiation-induced increase in comet parameters, which could be the result of protection to DNA under in vivo conditions of radiation exposure. Thus, it can be concluded from the results that asiaticoside can offer protection to DNA from radiation-induced alterations under in vitro, ex vivo, and in vivo conditions.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"39 1","pages":"353-61"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82070852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2015011903
Priyanka Sharma, P. Goyal
The present study was designed to evaluate the effect of green tea catechin (7500 µg/kg/animal/day) against cadmium-induced testicular dysfunctions and oxidative stress in the testes of mice. For this purpose, Swiss albino mice were divided into six groups: group I, negative control; group II, catechin-treated control; group III, cadmium chloride (CdCl2)-treated control; group IV, experimental group I; group V, experimental group II; and group VI, experimental group III. Animals from all of these groups were necropsied at various post-treatment intervals between 12 hours and 30 days for various biochemical alterations in the testes. CdCl2 intoxication resulted in a significant decline in testicular total proteins, cholesterol, and alkaline phosphatase, whereas acid phosphatase and lipid peroxidation exhibited a noticeable augmentation as compared to negative control. Catechin treatment effectively protected CdCl2-induced alterations in all such parameters throughout the experiment. Catechin was effective in reducing the CdCl2-induced augmentation of phase I (P450 and CYPB5) as well as phase II (DT-diaphorase and glutathione-S-transferase) enzymes in testes. Furthermore, CdCl2 intoxication was found to attenuate the antioxidant potential of testes, which was however augmented when supplemented with green tea extract. Compared to CdCl2-treated control mice, superoxide dismutase, glutathione peroxidase, glutathione, and catalase levels were significantly decreased in testes. Indeed, green tea catechin significantly increased testicular antioxidant enzymatic activities compared to those given CdCl2 alone. In conclusion, the use of green tea extract appeared to be beneficial to a great extent in inhibiting and restoring the testicular injuries induced by CdCl2 intoxication in mammals.
本研究旨在评价绿茶儿茶素(7500µg/kg/动物/天)对镉诱导的小鼠睾丸功能障碍和氧化应激的影响。为此，将瑞士白化病小鼠分为6组:1组为阴性对照;II组，儿茶素处理对照组;III组，氯化镉(CdCl2)处理对照;第四组，实验一组;V组，实验II组;第六组为实验第三组。所有这些组的动物在治疗后12小时至30天的不同时间间隔内进行尸检，以观察睾丸的各种生化变化。CdCl2中毒导致睾丸总蛋白、胆固醇和碱性磷酸酶显著下降，而与阴性对照相比，酸性磷酸酶和脂质过氧化反应明显增加。在整个实验过程中，儿茶素处理有效地保护了cdcl2诱导的所有这些参数的改变。儿茶素能有效降低cdcl2诱导的睾丸I期(P450和CYPB5)和II期(DT-diaphorase和谷胱甘肽- s -转移酶)酶的升高。此外，CdCl2中毒会减弱睾丸的抗氧化能力，而绿茶提取物则会增强睾丸的抗氧化能力。与cdcl2处理的对照组小鼠相比，睾丸超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽和过氧化氢酶水平显著降低。事实上，绿茶儿茶素与单独服用CdCl2的小鼠相比，显著提高了睾丸抗氧化酶的活性。综上所述，绿茶提取物在很大程度上有利于抑制和恢复哺乳动物CdCl2中毒引起的睾丸损伤。
{"title":"Ameliorative Effect of Green Tea Catechin Against Cadmium Chloride-Induced Testicular Toxicity in Mice.","authors":"Priyanka Sharma, P. Goyal","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2015011903","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2015011903","url":null,"abstract":"The present study was designed to evaluate the effect of green tea catechin (7500 µg/kg/animal/day) against cadmium-induced testicular dysfunctions and oxidative stress in the testes of mice. For this purpose, Swiss albino mice were divided into six groups: group I, negative control; group II, catechin-treated control; group III, cadmium chloride (CdCl2)-treated control; group IV, experimental group I; group V, experimental group II; and group VI, experimental group III. Animals from all of these groups were necropsied at various post-treatment intervals between 12 hours and 30 days for various biochemical alterations in the testes. CdCl2 intoxication resulted in a significant decline in testicular total proteins, cholesterol, and alkaline phosphatase, whereas acid phosphatase and lipid peroxidation exhibited a noticeable augmentation as compared to negative control. Catechin treatment effectively protected CdCl2-induced alterations in all such parameters throughout the experiment. Catechin was effective in reducing the CdCl2-induced augmentation of phase I (P450 and CYPB5) as well as phase II (DT-diaphorase and glutathione-S-transferase) enzymes in testes. Furthermore, CdCl2 intoxication was found to attenuate the antioxidant potential of testes, which was however augmented when supplemented with green tea extract. Compared to CdCl2-treated control mice, superoxide dismutase, glutathione peroxidase, glutathione, and catalase levels were significantly decreased in testes. Indeed, green tea catechin significantly increased testicular antioxidant enzymatic activities compared to those given CdCl2 alone. In conclusion, the use of green tea extract appeared to be beneficial to a great extent in inhibiting and restoring the testicular injuries induced by CdCl2 intoxication in mammals.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"11 1","pages":"335-52"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85445504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013806
Shruti Gade, N. Gandhi
Hypoxia inducible factor (HIF) is a key transcription factor responsible for imparting adaptability to the cancer cells growing in tumors. HIF induces the modulation of glucose metabolism, angiogenesis, and prosurvival signaling. Therefore, HIF is one of the attractive targets to treat solid tumors. Results presented in this study indicate that Baicalein (BA) inhibits HIF stabilization and also reduces its transcription activity in MCF-7 cells in vitro. Furthermore, BA was found to have antiproliferative ability as determined by the MTT assay and clonogenic survival. BA also induces apoptosis in MCF-7 cells at the concentration of 50 µM. We also report the radiosensitization of MCF-7 cells when they are treated with BA, resulting in higher γ-radiation-induced DNA damage. BA is extensively used in Chinese medicine and is known to be nontoxic at pharmacological doses. Our studies indicate that BA is one of the attractive natural compounds suitable for further evaluation as an adjuvant therapy.
{"title":"Baicalein Inhibits MCF-7 Cell Proliferation In Vitro, Induces Radiosensitivity, and Inhibits Hypoxia Inducible Factor.","authors":"Shruti Gade, N. Gandhi","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013806","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013806","url":null,"abstract":"Hypoxia inducible factor (HIF) is a key transcription factor responsible for imparting adaptability to the cancer cells growing in tumors. HIF induces the modulation of glucose metabolism, angiogenesis, and prosurvival signaling. Therefore, HIF is one of the attractive targets to treat solid tumors. Results presented in this study indicate that Baicalein (BA) inhibits HIF stabilization and also reduces its transcription activity in MCF-7 cells in vitro. Furthermore, BA was found to have antiproliferative ability as determined by the MTT assay and clonogenic survival. BA also induces apoptosis in MCF-7 cells at the concentration of 50 µM. We also report the radiosensitization of MCF-7 cells when they are treated with BA, resulting in higher γ-radiation-induced DNA damage. BA is extensively used in Chinese medicine and is known to be nontoxic at pharmacological doses. Our studies indicate that BA is one of the attractive natural compounds suitable for further evaluation as an adjuvant therapy.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"11 1","pages":"299-308"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82226300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013397
A. Ghio, E. Pavlisko, V. Roggli
We tested the postulate that iron homeostasis is altered among patients diagnosed to have asbestosis. Lung tissue from six individuals diagnosed to have had asbestosis at autopsy was stained for iron, ferritin, divalent metal transporter 1 (DMT1), and ferroportin 1 (FPN1). Slides from six individuals having pneumonectomy for lung cancer were employed as controls. Lung tissue from those patients with asbestosis demonstrated stainable iron, whereas control lung tissue did not. Staining for this metal was observed predominantly in airway and alveolar macrophages. Expression of the iron-related proteins ferritin, DMT1, and FPN1 was elevated in lung tissue from the six asbestosis patients relative to controls. This increased expression of iron-transport and iron-storage proteins was evident in both airway and alveolar epithelial cells. Asbestos bodies were abundant in lung tissue from patients diagnosed to have had asbestosis. While staining for iron, ferruginous bodies did not demonstrate uptake of antibodies for ferritin, DMT1, and FPN1. We conclude that iron homeostasis is altered in lung disease among those diagnosed to have asbestosis with an accumulation of the metal and a modified expression of iron-related proteins being evident.
{"title":"Iron and Iron-Related Proteins in Asbestosis.","authors":"A. Ghio, E. Pavlisko, V. Roggli","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013397","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2015013397","url":null,"abstract":"We tested the postulate that iron homeostasis is altered among patients diagnosed to have asbestosis. Lung tissue from six individuals diagnosed to have had asbestosis at autopsy was stained for iron, ferritin, divalent metal transporter 1 (DMT1), and ferroportin 1 (FPN1). Slides from six individuals having pneumonectomy for lung cancer were employed as controls. Lung tissue from those patients with asbestosis demonstrated stainable iron, whereas control lung tissue did not. Staining for this metal was observed predominantly in airway and alveolar macrophages. Expression of the iron-related proteins ferritin, DMT1, and FPN1 was elevated in lung tissue from the six asbestosis patients relative to controls. This increased expression of iron-transport and iron-storage proteins was evident in both airway and alveolar epithelial cells. Asbestos bodies were abundant in lung tissue from patients diagnosed to have had asbestosis. While staining for iron, ferruginous bodies did not demonstrate uptake of antibodies for ferritin, DMT1, and FPN1. We conclude that iron homeostasis is altered in lung disease among those diagnosed to have asbestosis with an accumulation of the metal and a modified expression of iron-related proteins being evident.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"24 1","pages":"277-85"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90301928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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