المؤلفون: Dakota B. Ward, Monica A. Valentovic, Dianne K. Anestis, Gary O. Rankin, John G. Ball, Debbie Preston, Christopher Racine, Travis Ferguson

المصدر: Toxicology. :47-55

مصطلحات موضوعية: Male, 0301 basic medicine, Kidney Cortex, Antioxidant, medicine.medical_treatment, Cell Separation, Pharmacology, Toxicology, medicine.disease_cause, Article, Antioxidants, Mixed Function Oxygenases, Nephrotoxicity, Protein Carbonylation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Lactate dehydrogenase, medicine, Animals, Cytochrome P-450 Enzyme Inhibitors, Enzyme Inhibitors, Biotransformation, Aniline Compounds, L-Lactate Dehydrogenase, biology, Cytochrome P450, Glutathione, Rats, Inbred F344, Rats, Oxidative Stress, 030104 developmental biology, chemistry, Biochemistry, Enzyme inhibitor, 030220 oncology & carcinogenesis, biology.protein, Kidney Diseases, Oxidative stress, Peroxidase

الوصف: Among the mono- and dichloroanilines, 3,5-Dichloroaniline (3,5-DCA) is the most potent nephrotoxicant in vivo and in vitro. However, the role of renal biotransformation in 3,5-DCA induced nephrotoxicity is unknown. The current study was designed to determine the in vitro nephrotoxic potential of 3,5-DCA in isolated renal cortical cells (IRCC) obtained from male Fischer 344 rats, and the role of renal bioactivation and oxidative stress in 3,5-DCA nephrotoxicity. IRCC (~4 million cells/ml) from male rats were exposed to 3,5-DCA (0-1.0 mM) for up to 120 min. In IRCC, 3,5-DCA was cytotoxic at 1.0 mM by 60 min as evidenced by the increased release of lactate dehydrogenase (LDH), but 120 min was required for 3,5-DCA 0.5 mM to increase LDH release. In subsequent studies, IRCC were exposed to a pretreatment (antioxidant or enzyme inhibitor) prior to exposure to 3,5-DCA (1.0 mM) for 90 min. Cytotoxicity induced by 3,5-DCA was attenuated by pretreatment with inhibitors of flavin-containing monooxygenase (FMO; methimazole, N-octylamine), cytochrome P450 (CYP; piperonyl butoxide, metyrapone), or peroxidase (indomethacin, mercaptosuccinate) enzymes. Use of more selective CYP inhibitors suggested that the CYP 2C family contributed to 3,5-DCA bioactivation. Antioxidants (glutathione, N-acetyl-L-cysteine, α-tocopherol, ascorbate, pyruvate) also attenuated 3,5-DCA nephrotoxicity, but oxidized glutathione levels and the oxidized/reduced glutathione ratios were not increased. These results indicate that 3,5-DCA may be activated via several renal enzyme systems to toxic metabolites, and that free radicals, but not oxidative stress, contribute to 3,5-DCA induced nephrotoxicity in vitro.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f5013d3b336c03cbebdeb199c9baca0aTest
https://doi.org/10.1016/j.tox.2016.01.006Test

المؤلفون: Noriyasu Hirasawa, Natsumi Mizuno, Yu Kishimoto, Sanki Asakawa, Taiki Sato, Masahiro Hiratsuka

المصدر: Toxicology. :37-45

مصطلحات موضوعية: Male, 0301 basic medicine, Lactate dehydrogenase A, medicine.medical_treatment, Inflammation, Real-Time Polymerase Chain Reaction, Toxicology, Prosthesis Implantation, Mice, 03 medical and health sciences, 0302 clinical medicine, Nickel, Leukocytes, medicine, Animals, education, Cells, Cultured, education.field_of_study, biology, Chemistry, Glucose transporter, Fibroblasts, Flow Cytometry, medicine.disease, Molecular biology, Mice, Inbred C57BL, 030104 developmental biology, Biochemistry, Cyclooxygenase 2, 030220 oncology & carcinogenesis, biology.protein, Monocarboxylate transporter 4, Microsome, GLUT1, medicine.symptom, Infiltration (medical), Prostaglandin E

الوصف: Many types of medical alloys include nickel (Ni), and the elution of Ni ions from these materials causes toxicities and inflammation. We have previously reported that inflammation enhances Ni elution, although the molecular mechanisms underlying this effect remain unclear. In this study, we investigated how inflammatory responses enhanced Ni elution in a wire-implantation mouse model. Subcutaneous implantation of Ni wire induced the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 ( mPGES-1 ) mRNA in the surrounding tissues. Immunostaining analysis showed that cells expressing COX-2 were mainly fibroblast-like cells 8 h after implantation of a Ni wire, but were mainly infiltrated leukocytes at 24 h. NiCl 2 induced the expression of COX-2 mRNA in primary fibroblasts, neutrophils, RAW 264 cells, and THP-1 cells, indicating that Ni ions can induce COX-2 expression in various types of cells. The elution of Ni ions from the implanted Ni wire at 8 h was reduced by dexamethasone (Dex), indomethacin (Ind), or celecoxib (Cel) treatment. Ni wire implantation induced an increase in mRNA levels for anaerobic glycolytic pathway components glucose transporter 1 ( GLUT1 ), hexokinase 2 ( HK2 ), lactate dehydrogenase A ( LDHA ), and monocarboxylate transporter 4 ( MCT4 ); the expression of these genes was also inhibited by Dex, Ind, and Cel. In primary fibroblasts, the expression of these mRNAs and the production of lactate were induced by NiCl 2 and further potentiated by PGE 2 . Furthermore, Ni wire-induced infiltration of inflammatory leukocytes was significantly reduced by Dex, Ind, or Cel. Depletion of neutrophils with a specific antibody caused reduction of both leukocyte infiltration and Ni elution. These results indicate that Ni ions eluted from wire induced COX-2 expression, which further promoted elution of Ni ions by increasing lactate production and leukocyte infiltration. Since COX inhibitors and Dex reduced the elution of Ni ions, these drugs may be useful for prevention of metal-related inflammation and allergy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91ac7ad45bff8821a43d00b6ac742999Test
https://doi.org/10.1016/j.tox.2016.07.013Test

المؤلفون: Bijan Naghibi, Ardeshir Talebi, Valiollah Hajhashemi, Diana Taheri, Taghi Ghafghazi

المصدر: Toxicology. 232:192-199

مصطلحات موضوعية: Male, medicine.medical_treatment, Intraperitoneal injection, CD13 Antigens, Pharmacology, Iron Chelating Agents, Toxicology, Antioxidants, Nephrotoxicity, Cyclic N-Oxides, Superoxide dismutase, Random Allocation, chemistry.chemical_compound, Vancomycin, Lactate dehydrogenase, Hydroxybenzoates, medicine, Animals, Urea, Drug Interactions, Rats, Wistar, Antibacterial agent, Creatinine, L-Lactate Dehydrogenase, biology, Histocytochemistry, 2,3-Dihydroxybenzoic acid, gamma-Glutamyltransferase, Rats, Biochemistry, chemistry, Toxicity, biology.protein, Kidney Diseases, Spin Labels

الوصف: One of the major adverse effects of vancomycin (VAN) is nephrotoxicity, which the mechanism is not fully understood. However, there is some evidence that oxidative injury could be involved in its pathogenesis. In this study, we examined two antioxidants 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) a superoxide dismutase mimetic and 2,3-dihydroxybenzoic acid (DHB) an iron chelator in VAN-induced nephrotoxicity in rats. DHB at doses of 50 and 100 mg/kg and tempol at doses of 7.5, 15 and 30 mg/kg were administered subcutaneously to rats 30 min prior to intraperitoneal injection of 200 mg/kg VAN. Drug administrations were done every 12 h for 7 days. In animals which received only VAN, the activity of urinary gamma-glutamyl-transferase (GGT) decreased and the activity of lactate dehydrogenase (LDH) in urine increased significantly compared to controls. Serum urea and creatinine (Cr) concentrations and the weight of animals' kidneys increased and body weights were decreased significantly in this group compared to controls. DHB at both doses normalized the GGT activity, but only at the higher dose restore the LDH activity. Both doses of DHB ameliorated the rise in serum urea and Cr concentrations and improved the changes in kidney and body weights significantly. Tempol did not show any beneficial effects at all. There were marked pathologic changes in tubules of kidneys of VAN treated animals. The tissue injury was prevented by both doses of DHB and there was almost no sign of tubular injury in 100 mg/kg treated group. Tempol in any doses could not prevent the tissue injury and there were significant differences in tissue injury in all tempol treated rats with controls. It seems that VAN-induced nephrotoxicity is at least partly due to free radical formation. Hydroxyl radicals might play a major role in VAN-induced nephrotoxicity, since an iron chelator (DHB) could reverse the adverse effects. However, production of other radicals such as superoxide is also probable.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::83ba856f958e0e93537d5f2ace23f821Test
https://doi.org/10.1016/j.tox.2007.01.005Test

المؤلفون: Yiqun Mo, Rong Wan, Sufan Chien, Qunwei Zhang, David J. Tollerud, Jianpu Wang

المصدر: Toxicology. 262:130-137

مصطلحات موضوعية: Blood Glucose, medicine.medical_specialty, Cell Survival, medicine.medical_treatment, Gene Expression, Toxicology, medicine.disease_cause, Diabetes Mellitus, Experimental, chemistry.chemical_compound, Internal medicine, Alloxan, Diabetes mellitus, Macrophages, Alveolar, medicine, Animals, Macrophage, RNA, Messenger, Cells, Cultured, chemistry.chemical_classification, Air Pollutants, Enzyme Precursors, COPD, Reactive oxygen species, L-Lactate Dehydrogenase, medicine.diagnostic_test, Chemistry, Urban Health, medicine.disease, Bronchoalveolar lavage, Cytokine, Endocrinology, Matrix Metalloproteinase 9, Gelatinases, Culture Media, Conditioned, Immunology, Cytokines, Particulate Matter, Rabbits, Reactive Oxygen Species, Bronchoalveolar Lavage Fluid, Oxidative stress

الوصف: Many epidemiological studies and animal experiments have shown that individuals with preexisting diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM) are more susceptible to particulate matter (PM)-related health problems. However, the mechanisms underlying this susceptibility are still unclear. PM has been shown to affect macrophage functions. We hypothesized that exposure to PM in the setting of DM and high glucose levels would result in enhanced macrophage activation. Rabbits were rendered diabetic with alloxan administered intravenously. Blood glucose concentration was measured daily for the first several weeks and weekly thereafter using a blood glucose meter. After 9 months of diabetes (blood glucose great than 450 mg/dl), rabbits were sacrificed and bronchoalveolar lavage was performed to collect alveolar macrophages. Alveolar macrophages were exposed in vitro to urban particulate matter SRM 1648 (U-PM). Our results showed that U-PM caused dose-dependent cytotoxic effects, and these effects were significantly higher in macrophages obtained from DM rabbits than those from normal rabbits. Reactive oxygen species (ROS) generation in macrophages from DM rabbits with exposure to U-PM was also greater than in macrophages from normal rabbits. Our results also showed that exposure of macrophages to U-PM caused an increase in cytokine mRNA expression level and activity of matrix metalloproteinase 9 (MMP-9), but not MMP-2, and that these effects were greater in macrophages from DM rabbits. These results demonstrate that U-PM caused severe oxidative stress in macrophages from DM rabbits and up-regulation of cytokine expression and MMP-9 activity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3dab36bbf5f18b010cf3e4eefa019d8fTest
https://doi.org/10.1016/j.tox.2009.05.019Test

المؤلفون: Adluri Ram Sudheer, Venugopal P. Menon, Shanmugavel Muthukumaran, Halagowder Devaraj, Nagarajan Devipriya

المصدر: Toxicology. 243:317-329

مصطلحات موضوعية: Male, Nicotine, Antioxidant, Coumaric Acids, DNA damage, Injections, Subcutaneous, medicine.medical_treatment, Blotting, Western, Pharmacology, Toxicology, Thiobarbituric Acid Reactive Substances, Antioxidants, Acetylcysteine, Lipid peroxidation, chemistry.chemical_compound, medicine, Animals, Rats, Wistar, Intubation, Gastrointestinal, Inflammation, chemistry.chemical_classification, Glutathione Peroxidase, L-Lactate Dehydrogenase, Molecular Structure, Superoxide Dismutase, Chemistry, Glutathione peroxidase, NF-kappa B, Glutathione, Alkaline Phosphatase, Catalase, Rats, Comet assay, Biochemistry, Cyclooxygenase 2, Toxicity, Comet Assay, Lipid Peroxidation, DNA Damage, medicine.drug

الوصف: We examined the effect of ferulic acid (FA), a naturally occurring phenolic compound on lipid peroxidation and endogenous antioxidant status, DNA damage and inflammation in nicotine-administered Wistar rats. The effect of FA against nicotine toxicity was compared with N-acetylcysteine (NAC), a well-known antioxidant. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5mg/kg body weight (5 days a week, for 22 weeks) and FA and NAC were given simultaneously by intragastric intubation for 22 weeks. Seventy two Wistar rats were divided into six groups: (i) control, (ii) nicotine, (iii) nicotine+FA (iv), nicotine+NAC, (v) FA and (vi) NAC. At the end of the experimental period, cellular damage was assessed by measuring the activities of lactate dehydrogenase and alkaline phosphatase in plasma, which were significantly elevated in nicotine-administered rats when compared with control group. Enhanced lipid peroxidation (evaluated by measuring the thiobarbituric acid reactive substances and hydroperoxides) was accompanied by a significant decrease in the endogenous antioxidant status viz., superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione in circulation, lung and liver of nicotine-treated rats when compared with control group. DNA single strand breaks (evaluated by comet assay) and frequency of micronuclei were significantly increased in peripheral blood of nicotine-treated rats when compared with control. Our Western blot analysis showed a significant increase in the expression of cyclooxygenase-2 and NF-kappaB in lung and liver of nicotine-treated rats. FA and NAC co-treated rats showed a significant decrease in the activities of circulatory lactate dehydrogenase and alkaline phosphatase, the levels of lipid peroxidative markers (in circulation, lung and liver), DNA single stranded breaks (comet parameters), micronuclei frequency (in the whole blood) and expression of cyclooxygenase-2 and Nf-kappaB (in lung and liver tissues), and significant increase in antioxidant status (in circulation, lung and liver). The protection of FA against nicotine-induced toxicity was merely equal to the effect of NAC. FA and NAC treatment alone did not produce any damage to control rats. Thus, we propose that FA exerts protective effect against nicotine toxicity by modulating the lipid peroxidation, inflammation, DNA damage and endogenous antioxidant status.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85d86aca187526c26db652c7de1ab996Test
https://doi.org/10.1016/j.tox.2007.10.016Test

المؤلفون: Shanmugavelu Muthukumaran, Namasivayam Nalini, Adluri Ram Sudheer, Venugopal P. Menon

المصدر: Toxicology. 243:207-215

مصطلحات موضوعية: Male, Nicotine, Antioxidant, Thiobarbituric acid, medicine.medical_treatment, Pharmacology, Kidney, Toxicology, Antioxidants, Lipid peroxidation, Superoxide dismutase, chemistry.chemical_compound, medicine, Animals, Rats, Wistar, Lung, chemistry.chemical_classification, L-Lactate Dehydrogenase, biology, Glutathione peroxidase, Body Weight, Glutathione, Alkaline Phosphatase, Oxidants, Acetylcysteine, Rats, Comet assay, Liver, Biochemistry, chemistry, Toxicity, biology.protein, Quercetin, DNA Damage

الوصف: We have investigated the protective effect of quercetin (QN) against nicotine-induced prooxidant and antioxidant imbalance in circulation, lung, liver and kidney of experimental rats. The protective effect of QN was compared with N-acetylcysteine (NAC), a well-known antioxidant. Male albino rats of Wistar stain were used for the experimental study. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg body weight (5 days a week, for 22 weeks) and QN was given simultaneously by intragastric intubations for 22 weeks. The body weight gain of rats during experimental period was significantly decreased in nicotine treated group, whereas QN co-treated rats significantly increased in their body weight. The levels of lipid peroxidative indices viz., thiobarbituric acid reactive substances and hydroperoxides, and nitric oxide in circulation, lung, liver and kidney of nicotine-treated rats were increased significantly when compared to normal, which were brought down to near normal in QN co-treated group. Endogenous antioxidant status viz., superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione were found to be significantly decreased in circulation, lung, liver and kidney of nicotine-treated group, which were significantly increased in QN-administered groups. The extent of DNA damage (evaluated by comet assay) was significantly increased in circulatory blood of nicotine-treated rats, which was effectively brought down by QN treatment. The protective effect of QN against nicotine toxicity was comparable to that of NAC. Our data suggest that QN exerts its protective effect by modulating the extent of lipid peroxidation and augmenting antioxidant defense system and thus protects the DNA in experimental animals.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::720e592f49ba496cece3eec4e8263901Test
https://doi.org/10.1016/j.tox.2007.10.006Test

المؤلفون: A.Ch. Pulla Reddy, Belur R. Lokesh

المصدر: Toxicology. 107:39-45

مصطلحات موضوعية: Male, Lipid Peroxides, Curcumin, medicine.medical_treatment, Pharmacology, Toxicology, Thiobarbituric Acid Reactive Substances, Lipid peroxidation, chemistry.chemical_compound, Oral administration, Lactate dehydrogenase, Eugenol, medicine, Animals, Aspartate Aminotransferases, Ferrous Compounds, Rats, Wistar, Antidote, L-Lactate Dehydrogenase, Lipid peroxide, Alanine Transaminase, Rats, Liver, chemistry, Biochemistry, Toxicity, Lipid Peroxidation, Injections, Intraperitoneal

الوصف: Male Wistar rats injected i.p. with 30 mg Fe2+/kg body weight show hepatic damage as measured by an increase in lipid peroxides which correlated with elevated serum enzymes, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and lactate dehydrogenase (LDH). Oral administration of spice principles, curcumin from turmeric (30 mg/kg body weight) or eugenol from cloves (100 mg/kg body weight), for 10 days lowered the liver and serum lipid peroxide levels, serum ALAT, ASAT and LDH, enhanced by i.p. injection of iron. This study indicates that curcumin or eugenol reduces the iron-induced hepatic damage by lowering lipid peroxidation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9891031542ab49fa07693e488075c11eTest
https://doi.org/10.1016/0300-483xTest(95)03199-p

المؤلفون: P. Stanely Mainzen Prince, M. Padmanabhan

المصدر: Toxicology. 224:128-137

مصطلحات موضوعية: Male, Lipid Peroxides, medicine.medical_specialty, Antioxidant, Heart Diseases, Thiobarbituric acid, medicine.medical_treatment, Glutathione reductase, Tocopherols, Ascorbic Acid, Toxicology, Thiobarbituric Acid Reactive Substances, Antioxidants, Superoxide dismutase, chemistry.chemical_compound, Internal medicine, Lactate dehydrogenase, medicine, Animals, Cysteine, Rats, Wistar, chemistry.chemical_classification, biology, Chemistry, Myocardium, Glutathione peroxidase, Isoproterenol, Glutathione, Adrenergic beta-Agonists, Ascorbic acid, Rats, Endocrinology, biology.protein

الوصف: The consumption of diets rich in plant foods are associated with a reduced risk of cardiovascular diseases. This study was aimed to evaluate the role of S-allylcysteine (SAC) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (150 mg/kg) to Wistar rats showed a significant decrease in the activities of marker enzymes such as creatine kinase, lactate dehydrogenase, aspartate and alanine transaminases in heart and a significant increase in the levels of thiobarbituric acid reactive substances and lipid hydroperoxides in plasma and heart. ISO-induced rats also showed a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase in heart and the levels of glutathione and ascorbic acid in plasma and heart. Oral administration of SAC (100 and 150 mg/kg) to ISO-treated rats daily for a period of 45 days caused a significant increase in the activities of marker enzymes and improved the antioxidant status by decreasing lipid peroxidative products and increasing the activities of antioxidant enzymes and the levels of nonenzyomic antioxidants. Administration of SAC to normal rats did not show any significant effect. Histopathological findings of the myocardial tissue showed a protective role of SAC in ISO-treated rats. The effect at a dose of 150 mg/kg of SAC was more pronounced than that of the dose 100 mg/kg and brought back all the parameters to near normal. The effect exerted by 100 mg/kg of SAC was similar to that of α-tocopherol (60 mg/kg). The results of our study show that SAC possesses antioxidant activity in ISO-induced experimental MI.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0147d8f8bc1f84cef42a48f935d4ce8dTest
https://doi.org/10.1016/j.tox.2006.04.039Test

المؤلفون: Theruvathil K. Sini, Sethumadhavan Santhosh, P.T. Mathew, Rangasamy Anandan

المصدر: Toxicology. 219:53-59

مصطلحات موضوعية: Male, Lipid Peroxides, Antioxidant, medicine.medical_treatment, Antitubercular Agents, Fatty Acids, Nonesterified, Pharmacology, Toxicology, Lipid peroxidation, chemistry.chemical_compound, Liver Function Tests, Lactate dehydrogenase, Isoniazid, medicine, Animals, Rats, Wistar, Triglycerides, Antibacterial agent, Chitosan, biology, Cholesterol, Acid phosphatase, Rats, Liver, Biochemistry, chemistry, biology.protein, Alkaline phosphatase, Lipid Peroxidation, Chemical and Drug Induced Liver Injury, Rifampin, medicine.drug

الوصف: We have studied the protective effect of chitosan on isoniazid- and rifampicin-induced hepatotoxicity with respect to the changes in the levels of diagnostic marker enzymes (in serum), lipid components and lipid peroxidation (in serum and liver). The oral administration of antitubercular drugs caused a significant elevation in the levels of diagnostic marker enzymes and cholesterol, triglycerides, free fatty acids and lipid peroxidation in serum and liver of experimental rats. There was a slight decline in the level of phospholipids in liver tissue also observed. Co-administration of chitosan significantly prevented the antitubercular drugs-induced elevation in the levels of serum diagnostic marker enzymes (alanine amino transferase, aspartate amino transferase, lactate dehydrogenase, acid phosphatase and alkaline phosphatase) in experimental groups of rats. It exerted a significant antilipidemic effect against isoniazid- and rifampicin-induced hepatitis by maintaining the levels cholesterol, triglycerides, free fatty acids and phospholipids in serum and liver at near normalcy. A tendency to prevent the isoniazid- and rifampicin-induced lipid peroxidation was also observed. The results of the present study indicated that the hepatoprotective effect of chitosan might be ascribable to its antilipidemic effect and/or antioxidant property.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::27f90cf101e0cc5f9d996133fdf0184fTest
https://doi.org/10.1016/j.tox.2005.11.001Test

المؤلفون: Xue-Jun Zhang, Tong Shen, Qi-Xing Zhu, Zhao-Zhao Liang, Rui Ding

المصدر: Toxicology. 209:55-67

مصطلحات موضوعية: Keratinocytes, Male, Tetrachloroethylene, Cell Survival, medicine.medical_treatment, Toxicology, medicine.disease_cause, Superoxide dismutase, Lipid peroxidation, chemistry.chemical_compound, Lactate dehydrogenase, medicine, Humans, Vitamin E, Viability assay, Cytotoxicity, Cells, Cultured, Dose-Response Relationship, Drug, biology, Chemistry, Malondialdehyde, Molecular biology, Trichloroethylene, Epidermal Cells, Biochemistry, Cytoprotection, biology.protein, Epidermis, Oxidative stress

الوصف: Trichloroethylene (TCE) and perchloroethylene (PERC), the most common alkenyl halides, have been extensively used in industry, and can cause skin damage. To evaluate their cytotoxic potential on skin, the effects of these agents on the normal human epidermal keratinocytes (NHEK) were investigated. Their action on cell viability, membrane integrity and lipid peroxidation (LPO) was assessed by neutral red uptake (NRU) assay, lactate dehydrogenase (LDH) release test and measurement of malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. In addition, the protective effect of antioxidatant vitamin E on the cytotoxicity was also studied. Incubation of NHEK with various concentrations (0.01-31.6 mM) of TCE or PERC caused a dose-dependent decrease in cell viability, with 80% reduction at 31.6 mM. NR50 values from the cytotoxicity assay was found to be 4.53 and 2.16 mM for TCE and PERC, respectively. A time- and concentration- dependent release of LDH were observed at 1, 2, 3, 4 h after cells were exposed to different doses of TCE or PERC. These agents also caused an increase of MDA, whilst an inhibition of SOD activity, in a concentration-dependent manner. Pre-treatment of the cells with vitamin E at 10-200 mM dose-dependently attenuated the cytotoxic effect of TCE or PERC. Pre-treatment with vitamin E also reversed subsequent TCE or PERC-induced release of LDH, elevation of lipid peroxidation and decline of anti-oxidant enzyme activities. These results suggest that TCE and PERC could induce cytotoxicity to NHEK associated with oxidative stress and antioxidatant vitamin E could effectively protect NHEK from TCE- or PERC-induced cytotoxicity, which may be associated to the superoxide scavenging effect and enhancement of anti-oxidant enzyme activities.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b04095a5ce45f7dfc6f22cf56cc17d3Test
https://doi.org/10.1016/j.tox.2004.12.006Test