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Changes in blood antioxidant status in humans during occupational exposure to coal fly ash (CFA)
S62
Abstracts / Toxicology Letters 221S (2013) S59–S256
P02-04 Changes in blood antioxidant status in humans during occupational exposure to coal fly ash (CFA) Lulzim Zeneli 1,∗ , Majlinda Ajvazi 2 , Martina Piasek 3 , Jasna Jurasovic´ 3 , Leonard Kurti 1 , Hidajet Pac¸arizi 1 , Nexhat Daci 2 1
Institute of Biochemistry, Faculty of Medicine, University of Prishtina, Kosovo, 2 Department of Chemistry, University of Prishtina, Kosovo, 3 Institute for Medical Research and Occupational Health, Zagreb, Croatia Purpose: Different pollutant (including particular mater of fly ash) has been reported to cause oxidative stress due to generation of free radicals and alteration in antioxidant defense mechanisms. The present paper aims to highlight the changes in blood antioxidant status (red blood cells antioxidant enzymes such as SOD, GSH-Px and plasma vitamin-C) including selected biochemical parameters of workers occupationally exposed to coal flying ash (CFA). Methods: Seventy workers occupationally exposed to fly ash (investigation group) and 27 without occupational exposure (control group) was recruited into this study. Investigation group was divided into four classes, according to occupational history. Class-I (includes workers with work experience <10 years), classII (10–20 years), class-III (21–30 years) and class-IV (>30 years). Results: The results show that, the investigation group presented lower levels of superoxide dismutase SOD (p = 0.002), glutathione peroxidases GSH-Px (p = <0.001), GSH-Px/SOD ratio (<0.001) and vitamin-C (p = <0.001) as compared to control group. In the investigated group, between class-I and II exists a significant difference in the level of GSH-Px (p = 0.04) and GSH-Px/SOD ratio (p = 0.004), where we have significant decrease of activity of GSH-Px and GSHPx/SOD ratio, whereas between the class-II and III, III and IV not exists such a significant difference. Changes are expressed also in biochemical parameters of blood serum such as: triglycerides, total cholesterol, creatinine, urea, lactate dehydrogenase and creatine kinase. Conclusion: It can be concluded that red blood cells antioxidant enzymes and plasma vitamin-C can be used as biomarkers in monitoring acute occupational exposure of the workers of coal processing industry. http://dx.doi.org/10.1016/j.toxlet.2013.05.025
P02-05 Comparative study between apoptotic and proliferative markers in dexamethasone-dependent and physiological thymic atrophy in cattle G.B. Richelmi ∗ , C. Maurella, M. Pezzolato, D. Longo, S. Meistro, E. Bozzetta Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Torino, Italy Corticosteroids are widely used in veterinary medicine for their anti-inflammatory properties; due to the health risk for consumers, administration of these compounds is strictly regulated (Commission Regulation (EU) 37/2010) and it is forbidden in food-producing animals for growth promotion. In the attempt to develop an accurate biological method detecting illicit treatments, we have previously reported significant thymic morphological parameters in veal calves administered at low-dose dexamethasone versus control animals (Bozzetta et al., 2011).
In this study we performed two different immunohistochemical stains to have a new insight into the differences between patterns of expression of apoptosis (Cleaved Lamin A) and proliferative (Ki 67) markers related to physiological vs dexamethasone dependent apoptosis and regeneration of the thymus. Immunohistochemistry was performed on thymus from five dexamethasone treated calves (group A) (0.4 mg/day for 20 days), five control calves (group B) and five control beef cattle (group C), sampled at slaughterhouse two weeks later the last administration. A pathologist counted the total number of apoptotic LAMIN A and proliferative markers Ki67 positive cells in five representative microscopic high-power fields in each immunostained thymus section. The results were statistically analyzed: no significative differences were found between groups A and B for each marker. A higher apoptotic index was found in group C in respect to group B, while no difference in regeneration index was found between these two groups. According to our preliminary data we can conclude that these parameters would not represent candidate markers for drugrelated atrophy, while they correlate with physiological involution. http://dx.doi.org/10.1016/j.toxlet.2013.05.026
P02-06 Comparison of two commonly used rat strains for preclinical toxicity testing on predictive biomarkers for nephrotoxicity after cisplatin treatment M. Kunze 1,∗ , K. Weber 2 , I. Schuster 1 , S. Meier 1 , A.L. Leoni 1 1 BSL BIOSERVICE Scientific Laboratories GmbH, Behringstr. 6/8, 82152 Planegg, Munich, Germany, 2 AnaPath GmbH, Buchsweg 56, 4625 Oberbuchsiten, Switzerland
Drug induced acute kidney injury (DIKI) is one of the major causes why drug development fails or drugs need to be withdrawn from the market. For years, the most common approaches to detect early changes in kidney function rely on measurement of elevated serum creatinine and blood urea nitrogen (BUN). The FDA, EMA and PMDA have recently approved seven kidney biomarkers which signal nephrotoxicity and are considered acceptable in the context of non-clinical drug development for the detection of drug induced acute renal toxicity, either tubular or glomerular with associated tubular involvement. The aim of the study was to investigate whether or not there are differences in the two most commonly used rat strains for preclinical toxicity testing, the Sprague Dawley rat and the Wistar Hannover rat, with regards on the effectiveness to predict early renal injury with selected biomarkers, such as KIM-1, Cystatin C, Clusterin, Albumin, Lipocalin-2/NGAL from urine and creatinine and urea from blood. Male and female rats of both strains received a single intraperitoneal dose of 15 mg/kg bw cis-diammindichloroplatin (II) (cisplatin), which is known to be a potent nephrotoxic agent. Blood and urine were collected prior to the first administration and at defined time points up to 14 days after the treatment. Test animals were sacrificed at the defined time points to perform a macroscopic and microscopic evaluation of the kidneys, in order to correlate these findings with the results from the non-invasive biomarker quantification. http://dx.doi.org/10.1016/j.toxlet.2013.05.027
Abstracts / Toxicology Letters 221S (2013) S59–S256
P02-04 Changes in blood antioxidant status in humans during occupational exposure to coal fly ash (CFA) Lulzim Zeneli 1,∗ , Majlinda Ajvazi 2 , Martina Piasek 3 , Jasna Jurasovic´ 3 , Leonard Kurti 1 , Hidajet Pac¸arizi 1 , Nexhat Daci 2 1
Institute of Biochemistry, Faculty of Medicine, University of Prishtina, Kosovo, 2 Department of Chemistry, University of Prishtina, Kosovo, 3 Institute for Medical Research and Occupational Health, Zagreb, Croatia Purpose: Different pollutant (including particular mater of fly ash) has been reported to cause oxidative stress due to generation of free radicals and alteration in antioxidant defense mechanisms. The present paper aims to highlight the changes in blood antioxidant status (red blood cells antioxidant enzymes such as SOD, GSH-Px and plasma vitamin-C) including selected biochemical parameters of workers occupationally exposed to coal flying ash (CFA). Methods: Seventy workers occupationally exposed to fly ash (investigation group) and 27 without occupational exposure (control group) was recruited into this study. Investigation group was divided into four classes, according to occupational history. Class-I (includes workers with work experience <10 years), classII (10–20 years), class-III (21–30 years) and class-IV (>30 years). Results: The results show that, the investigation group presented lower levels of superoxide dismutase SOD (p = 0.002), glutathione peroxidases GSH-Px (p = <0.001), GSH-Px/SOD ratio (<0.001) and vitamin-C (p = <0.001) as compared to control group. In the investigated group, between class-I and II exists a significant difference in the level of GSH-Px (p = 0.04) and GSH-Px/SOD ratio (p = 0.004), where we have significant decrease of activity of GSH-Px and GSHPx/SOD ratio, whereas between the class-II and III, III and IV not exists such a significant difference. Changes are expressed also in biochemical parameters of blood serum such as: triglycerides, total cholesterol, creatinine, urea, lactate dehydrogenase and creatine kinase. Conclusion: It can be concluded that red blood cells antioxidant enzymes and plasma vitamin-C can be used as biomarkers in monitoring acute occupational exposure of the workers of coal processing industry. http://dx.doi.org/10.1016/j.toxlet.2013.05.025
P02-05 Comparative study between apoptotic and proliferative markers in dexamethasone-dependent and physiological thymic atrophy in cattle G.B. Richelmi ∗ , C. Maurella, M. Pezzolato, D. Longo, S. Meistro, E. Bozzetta Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Torino, Italy Corticosteroids are widely used in veterinary medicine for their anti-inflammatory properties; due to the health risk for consumers, administration of these compounds is strictly regulated (Commission Regulation (EU) 37/2010) and it is forbidden in food-producing animals for growth promotion. In the attempt to develop an accurate biological method detecting illicit treatments, we have previously reported significant thymic morphological parameters in veal calves administered at low-dose dexamethasone versus control animals (Bozzetta et al., 2011).
In this study we performed two different immunohistochemical stains to have a new insight into the differences between patterns of expression of apoptosis (Cleaved Lamin A) and proliferative (Ki 67) markers related to physiological vs dexamethasone dependent apoptosis and regeneration of the thymus. Immunohistochemistry was performed on thymus from five dexamethasone treated calves (group A) (0.4 mg/day for 20 days), five control calves (group B) and five control beef cattle (group C), sampled at slaughterhouse two weeks later the last administration. A pathologist counted the total number of apoptotic LAMIN A and proliferative markers Ki67 positive cells in five representative microscopic high-power fields in each immunostained thymus section. The results were statistically analyzed: no significative differences were found between groups A and B for each marker. A higher apoptotic index was found in group C in respect to group B, while no difference in regeneration index was found between these two groups. According to our preliminary data we can conclude that these parameters would not represent candidate markers for drugrelated atrophy, while they correlate with physiological involution. http://dx.doi.org/10.1016/j.toxlet.2013.05.026
P02-06 Comparison of two commonly used rat strains for preclinical toxicity testing on predictive biomarkers for nephrotoxicity after cisplatin treatment M. Kunze 1,∗ , K. Weber 2 , I. Schuster 1 , S. Meier 1 , A.L. Leoni 1 1 BSL BIOSERVICE Scientific Laboratories GmbH, Behringstr. 6/8, 82152 Planegg, Munich, Germany, 2 AnaPath GmbH, Buchsweg 56, 4625 Oberbuchsiten, Switzerland
Drug induced acute kidney injury (DIKI) is one of the major causes why drug development fails or drugs need to be withdrawn from the market. For years, the most common approaches to detect early changes in kidney function rely on measurement of elevated serum creatinine and blood urea nitrogen (BUN). The FDA, EMA and PMDA have recently approved seven kidney biomarkers which signal nephrotoxicity and are considered acceptable in the context of non-clinical drug development for the detection of drug induced acute renal toxicity, either tubular or glomerular with associated tubular involvement. The aim of the study was to investigate whether or not there are differences in the two most commonly used rat strains for preclinical toxicity testing, the Sprague Dawley rat and the Wistar Hannover rat, with regards on the effectiveness to predict early renal injury with selected biomarkers, such as KIM-1, Cystatin C, Clusterin, Albumin, Lipocalin-2/NGAL from urine and creatinine and urea from blood. Male and female rats of both strains received a single intraperitoneal dose of 15 mg/kg bw cis-diammindichloroplatin (II) (cisplatin), which is known to be a potent nephrotoxic agent. Blood and urine were collected prior to the first administration and at defined time points up to 14 days after the treatment. Test animals were sacrificed at the defined time points to perform a macroscopic and microscopic evaluation of the kidneys, in order to correlate these findings with the results from the non-invasive biomarker quantification. http://dx.doi.org/10.1016/j.toxlet.2013.05.027