Pub Date : 2000-10-01DOI: 10.1080/107691800317283680
H. Shimada, T. Adachi, M. Waalkes
Previously, we reported that the antiandrogen cyproterone acetate (CA) modifies cadmium (Cd) distribution and metallothionein (MT) induction in mice given a non-toxic dose of Cd (10 w mol Cd/kg, sc). We have also observed that CA pretreatment will reduce Cd toxicity in in vitro systems. Thus, since the liver is a primary target of acute Cd toxicity, the effects of CA pretreatment on the acute hepatotoxicity of Cd in vivo were studied in male C57 mice. Mice were pretreated with CA (10 mg/kg, sc, at - 48, - 24, and 0 h) prior to Cd (35 or 45 w mol Cd/kg, at 0 h). Cd alone (35 or 45 w mol Cd/kg) induced significant increases in serum alanine aminotransferase (ALT) activity, indicative of hepatotoxicity, 24 h after injection. However, CA pretreatment either prevented (at 35 w mol Cd/kg) or significantly reduced (at 45 w mol Cd/kg) Cd-induced increases in serum ALT. Based on serum creatinine levels, Cd alone was not acutely nephrotoxic. Thus, CA pretreatment substantially reduced the hepatotoxic effects of Cd. CA pretreatment had no effect on hepatic Cd levels 24 h after Cd exposure. The hepatic levels of zinc, a metal known to antagonize Cd toxicity, were modestly altered by CA pretreatment, but not in a consistent fashion. Cd alone markedly increased hepatic MT, a metal-binding protein often associated with tolerance to Cd, 24 h after exposure. CA pretreatment alone did not alter hepatic MT levels and pretreatment with CA before Cd did not alter hepatic levels of MT compared to Cd alone 24 h after injection of the metal. To further examine the tolerance to Cd induced by CA, the effects of CA pretreatment on hepatic Cd levels at early stages were investigated. Hepatic Cd levels were significantly decreased by CA pretreatment 8 h after Cd treatment and returned to control levels by 16 h. These results indicate that CA can substantially reduce the hepatotoxic effects of Cd in C57 mice without activating MT synthesis. The early decreases in liver Cd content may be critical to decreasing the adverse effect of Cd in the liver. Thus, it appears CA induces tolerance to Cd through altered biokinetics and in a manner not involving the MT system.
先前，我们报道了抗雄激素醋酸环丙孕酮(CA)在给予无毒剂量Cd (10 w mol Cd/kg, sc)的小鼠中改变镉(Cd)的分布和金属硫蛋白(MT)的诱导。我们还观察到CA预处理将降低体外系统中的Cd毒性。因此，由于肝脏是急性Cd毒性的主要靶点，我们在雄性C57小鼠体内研究了CA预处理对Cd急性肝毒性的影响。小鼠在注射Cd(35或45 w mol Cd/kg, 0 h)之前先注射CA (10 mg/kg, sc， - 48、- 24和0 h)。注射Cd(35或45 w mol Cd/kg)后24 h，血清丙氨酸转氨酶(ALT)活性显著升高，表明肝毒性。然而，CA预处理可以防止(35 w mol Cd/kg)或显著降低(45 w mol Cd/kg) Cd诱导的血清ALT升高。基于血清肌酐水平，单独Cd没有急性肾毒性。因此，CA预处理大大降低了Cd的肝毒性作用。CA预处理对Cd暴露后24小时的肝脏Cd水平没有影响。肝内锌(一种已知能拮抗Cd毒性的金属)水平被CA预处理适度改变，但不一致。Cd在暴露24小时后显著增加肝脏MT, MT是一种金属结合蛋白，通常与Cd耐受性有关。单独的CA预处理不会改变肝脏MT水平，并且在注射金属24小时后，与单独的Cd相比，CA预处理不会改变肝脏MT水平。为了进一步研究CA诱导的Cd耐受性，研究了CA预处理对早期肝脏Cd水平的影响。在Cd处理后8 h, CA预处理可显著降低肝脏Cd水平，并在16 h后恢复到对照水平。这些结果表明，CA可以在不激活MT合成的情况下显著降低Cd对C57小鼠的肝毒性作用。肝脏Cd含量的早期降低可能对降低Cd在肝脏中的不良影响至关重要。因此，CA通过改变生物动力学诱导对Cd的耐受性，而不涉及MT系统。
{"title":"HEPATOPROTECTIVE EFFECTS OF CYPROTERONE ACETATE IN MICE; MINIMAL ROLE OF METALLOTHIONEIN","authors":"H. Shimada, T. Adachi, M. Waalkes","doi":"10.1080/107691800317283680","DOIUrl":"https://doi.org/10.1080/107691800317283680","url":null,"abstract":"Previously, we reported that the antiandrogen cyproterone acetate (CA) modifies cadmium (Cd) distribution and metallothionein (MT) induction in mice given a non-toxic dose of Cd (10 w mol Cd/kg, sc). We have also observed that CA pretreatment will reduce Cd toxicity in in vitro systems. Thus, since the liver is a primary target of acute Cd toxicity, the effects of CA pretreatment on the acute hepatotoxicity of Cd in vivo were studied in male C57 mice. Mice were pretreated with CA (10 mg/kg, sc, at - 48, - 24, and 0 h) prior to Cd (35 or 45 w mol Cd/kg, at 0 h). Cd alone (35 or 45 w mol Cd/kg) induced significant increases in serum alanine aminotransferase (ALT) activity, indicative of hepatotoxicity, 24 h after injection. However, CA pretreatment either prevented (at 35 w mol Cd/kg) or significantly reduced (at 45 w mol Cd/kg) Cd-induced increases in serum ALT. Based on serum creatinine levels, Cd alone was not acutely nephrotoxic. Thus, CA pretreatment substantially reduced the hepatotoxic effects of Cd. CA pretreatment had no effect on hepatic Cd levels 24 h after Cd exposure. The hepatic levels of zinc, a metal known to antagonize Cd toxicity, were modestly altered by CA pretreatment, but not in a consistent fashion. Cd alone markedly increased hepatic MT, a metal-binding protein often associated with tolerance to Cd, 24 h after exposure. CA pretreatment alone did not alter hepatic MT levels and pretreatment with CA before Cd did not alter hepatic levels of MT compared to Cd alone 24 h after injection of the metal. To further examine the tolerance to Cd induced by CA, the effects of CA pretreatment on hepatic Cd levels at early stages were investigated. Hepatic Cd levels were significantly decreased by CA pretreatment 8 h after Cd treatment and returned to control levels by 16 h. These results indicate that CA can substantially reduce the hepatotoxic effects of Cd in C57 mice without activating MT synthesis. The early decreases in liver Cd content may be critical to decreasing the adverse effect of Cd in the liver. Thus, it appears CA induces tolerance to Cd through altered biokinetics and in a manner not involving the MT system.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85173516","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 : 2000-10-01DOI: 10.1080/107691800317283653
B. Ballantyne, J. C. Norris, P. Losco
5-Vinyl-2-norbornene (VNB: CAS Number 3048-64-4) is an industrial chemical with a potential for exposure to the vapor. To determine any hazards from repeated exposure to the vapor a subchronic exposure study was conducted in which male and female Sprague Dawley rats were exposed to VNB vapor for 6 hours per day, 5 days per week for 14 weeks at mean concentrations of 0, 5, 25.5, and 152 ppm. Subgroups at 0 and 152 ppm were kept for a 4-week post-exposure recovery period. This study was preceeded by a 9-day repeated vapor study in which male and female rats were exposed to mean concentrations of 50, 147, and 352 ppm. In both the 9-day and subchronic studies there were no significant exposure-related effects with respect to signs, mortality, body weights, serum chemistry, or urinalysis. The only hematological effect was an increase in the mean corpuscular volume and mean corpuscular hemoglobin in male rats of the 147 and 352 ppm groups. There were exposure-related increases in liver weights with the 9-day study, but no evidence for liver pathology based on serum chemistry and histology. Liver weights were also increased for males of the 152 ppm group in the subchronic study. Kidney weights were increased in an exposure concentration-related manner for the males of the 9-day study, and for 152 ppm males of the subchronic study. The only histopathological finding was proximal renal tubular hyaline droplet nephropathy in male rats. In the 9-day study, this was present in an exposure concentration-related manner.At 150 and 350 ppm this resulted in scattered areas of proximal tubular necrosis, but there was no serum chemistry or urinalysis evidence for renal dysfunction. At the end of the subchronic exposure period, minimal to mild hyaline droplet nephropathy was seen at 25.5 and 152 ppm, but not at 5 ppm, in the male rats. At the end of the 4-week recovery period, no hyaline droplet nephropathy was seen at any exposure concentration. An association of the nephropathy with f 2u -globulin was demonstrated for male rats of the 9-day study.
{"title":"SUBCHRONIC REPEATED VAPOR EXPOSURE TOXICITY OF 5-VINYL-2-NORBORNENE","authors":"B. Ballantyne, J. C. Norris, P. Losco","doi":"10.1080/107691800317283653","DOIUrl":"https://doi.org/10.1080/107691800317283653","url":null,"abstract":"5-Vinyl-2-norbornene (VNB: CAS Number 3048-64-4) is an industrial chemical with a potential for exposure to the vapor. To determine any hazards from repeated exposure to the vapor a subchronic exposure study was conducted in which male and female Sprague Dawley rats were exposed to VNB vapor for 6 hours per day, 5 days per week for 14 weeks at mean concentrations of 0, 5, 25.5, and 152 ppm. Subgroups at 0 and 152 ppm were kept for a 4-week post-exposure recovery period. This study was preceeded by a 9-day repeated vapor study in which male and female rats were exposed to mean concentrations of 50, 147, and 352 ppm. In both the 9-day and subchronic studies there were no significant exposure-related effects with respect to signs, mortality, body weights, serum chemistry, or urinalysis. The only hematological effect was an increase in the mean corpuscular volume and mean corpuscular hemoglobin in male rats of the 147 and 352 ppm groups. There were exposure-related increases in liver weights with the 9-day study, but no evidence for liver pathology based on serum chemistry and histology. Liver weights were also increased for males of the 152 ppm group in the subchronic study. Kidney weights were increased in an exposure concentration-related manner for the males of the 9-day study, and for 152 ppm males of the subchronic study. The only histopathological finding was proximal renal tubular hyaline droplet nephropathy in male rats. In the 9-day study, this was present in an exposure concentration-related manner.At 150 and 350 ppm this resulted in scattered areas of proximal tubular necrosis, but there was no serum chemistry or urinalysis evidence for renal dysfunction. At the end of the subchronic exposure period, minimal to mild hyaline droplet nephropathy was seen at 25.5 and 152 ppm, but not at 5 ppm, in the male rats. At the end of the 4-week recovery period, no hyaline droplet nephropathy was seen at any exposure concentration. An association of the nephropathy with f 2u -globulin was demonstrated for male rats of the 9-day study.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74167789","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 : 2000-10-01DOI: 10.1080/107691800317283662
E. Novelli, S. Marques, J. A. Almeida, Y. S. Diniz, L. Faine, B. Ribas
The presence of toxic substances in the workplace environment requires systematic evaluation of exposure and health status in exposed subjects. Cadmium is a highly toxic element found in water. Although free mediated cellular damage and reactive oxygen species (ROS), had been theorized as contributing to the cadmium mechanism of toxicity, and recent investigations have established that free radicals may be important contributors to cardiac dysfunction, there is little information on the effect of cadmium exposure on markers of oxidative stress in cardiac tissue. Cadmium exposure (Cd 2+ - 100 mg/l - from CdCl 2 ) in drinking water, during 15 days, significantly increased lipoperoxide and decreased the activities of superoxide dismutase and glutathione peroxidase. No alterations were observed in catalase activity in heart of rats with cadmium exposure. We also observed decreased glycogen and glucose concentration and increased total lipid content in cardiac tissue of rats with cadmium exposure. The decreased activities of alanine transaminase and aspartate transaminase reflected decreased metabolic protein degradation, and increased lactate dehydrogenase activity was related with increases in capacity of glycolysis. Since the metabolic pathways were altered by cadmium exposure, we can conclude that Cd 2+ exposure induced ROS and initiate some series of events that occur in the heart and resulted in metabolic pathways alterations.
{"title":"TOXIC MECHANISM OF CADMIUM EXPOSURE ON CARDIAC TISSUE","authors":"E. Novelli, S. Marques, J. A. Almeida, Y. S. Diniz, L. Faine, B. Ribas","doi":"10.1080/107691800317283662","DOIUrl":"https://doi.org/10.1080/107691800317283662","url":null,"abstract":"The presence of toxic substances in the workplace environment requires systematic evaluation of exposure and health status in exposed subjects. Cadmium is a highly toxic element found in water. Although free mediated cellular damage and reactive oxygen species (ROS), had been theorized as contributing to the cadmium mechanism of toxicity, and recent investigations have established that free radicals may be important contributors to cardiac dysfunction, there is little information on the effect of cadmium exposure on markers of oxidative stress in cardiac tissue. Cadmium exposure (Cd 2+ - 100 mg/l - from CdCl 2 ) in drinking water, during 15 days, significantly increased lipoperoxide and decreased the activities of superoxide dismutase and glutathione peroxidase. No alterations were observed in catalase activity in heart of rats with cadmium exposure. We also observed decreased glycogen and glucose concentration and increased total lipid content in cardiac tissue of rats with cadmium exposure. The decreased activities of alanine transaminase and aspartate transaminase reflected decreased metabolic protein degradation, and increased lactate dehydrogenase activity was related with increases in capacity of glycolysis. Since the metabolic pathways were altered by cadmium exposure, we can conclude that Cd 2+ exposure induced ROS and initiate some series of events that occur in the heart and resulted in metabolic pathways alterations.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76850585","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 : 2000-10-01DOI: 10.1080/107691800317283699
S. Baskin, George S Behonick, R. J. Schafer, M. Novak, C. Arroyo
The acute hemodynamic effects of organophosphate (OP) intoxication include positive chronotropic and inotropic changes along with increases in intraventricular pressure and coronary blood flow. These observations are consistent with an enhanced sympathetic tone that correlates neurogenic cardiomyopathy to adrenergic overactivity and subsequent, focal catecholamine (CA) release and cellular oxidative stress. Several mechanisms have been proposed to explain the cardiotoxicity associated with elevated CA concentrations. However, it is suggested that the oxidative metabolites of CA's, rather than (or in addition to) the parent CA's per se, may initiate or be in part responsible for the cardiotoxicity. The chromatographic profile of adrenochrome (1) and adrenolutin (2) (Figure 1) are described in this study in an isocratic, reverse phase HPLC method using UV/VIS and electrochemical (EC) detection. The aqueous adrenochrome standard shows a retention time of 1.9 minutes under employed conditions. Furthermore, using a flow rate of 0.6 mL/min and a UV/VIS detector set at a wavelength of 490 nm, several chromatographic peaks were detected, indicative of different species after injection of the aqueous adrenolutin standard. A similar multiple peak chromatographic profile was observed with EC detection. We hypothesized from the literature and observed complexity of the chromatogram (i.e. multiple intermediate species of the adrenolutin) that adrenolutin is being autooxidized over time. Based upon EPR spin trapping, we found the generation of a carbon-centered radical at the C-2 position that will interact with oxygen to give an intermediate peroxy radical. This may be eventually transformed to 5,6-dihydroxy-1-methyl-2,3-indoledione. The production of these proposed carbon- and oxygen-centered radicals in the autooxidation of adrenolutin was confirmed by spin trapping experiments using the spin trap, f -phenyl N-tert-butyl nitrone (PBN). When adrenolutin is dissolved in water at neutral pH in the presence of PBN, two different EPR spectra of PBN adducts are obtained. One observed PBN adduct has hyperfine splitting constants (hfsc's) of a N = 1.54 mT, a g H = 0.40 mT, and a n H = 0.13 mT; the other observed PBN adduct H H has the following hfsc's a N = 1.50 mT and a g H = 0.33 mT. The detection of these H reactive intermediates during the continued autooxidation of adrenolutin may account for the biochemical toxicity of catecholamine metabolism. These methods may allow for the quantification and/or characterization of the cardiotoxicity observed after organophosphate (OP) intoxication.
有机磷(OP)中毒的急性血流动力学影响包括正性变时性和正性肌力变化，并伴有心室压和冠状动脉血流的增加。这些观察结果与神经源性心肌病与肾上腺素能过度活动以及随后的局灶性儿茶酚胺(CA)释放和细胞氧化应激相关的交感神经张力增强是一致的。已经提出了几种机制来解释与CA浓度升高相关的心脏毒性。然而，这表明CA的氧化代谢物，而不是(或除了)亲本CA本身，可能启动或部分负责心脏毒性。本研究采用UV/VIS和电化学(EC)检测等容反相高效液相色谱法，描述了肾上腺素色素(1)和肾上腺素(2)的色谱图谱(图1)。在使用条件下，水相肾上腺素标准品的保留时间为1.9分钟。采用流速为0.6 mL/min，波长为490 nm的UV/VIS检测器，检测到若干色谱峰，表明肾上腺素水样注射液后的不同种类。用EC检测观察到类似的多峰色谱谱图。我们根据文献和观察到的色谱复杂性(即肾上腺素的多种中间物质)假设肾上腺素随着时间的推移被自氧化。基于EPR自旋捕获，我们发现在C-2位置产生碳中心自由基，并与氧相互作用生成中间过氧自由基。这可能最终转化为5,6-二羟基-1-甲基-2,3-吲哚二酮。这些碳中心自由基和氧中心自由基的产生在肾上腺素自氧化过程中得到了自旋捕获实验的证实，自旋捕获实验使用的自旋诱捕剂，f -苯基n-叔丁基硝基(PBN)。当肾上腺素在中性pH下溶于PBN存在的水中时，得到了PBN加合物的两种不同的EPR谱。一种观察到的PBN加合物具有超细分裂常数(hfsc): a N = 1.54 mT, a g H = 0.40 mT, a N H = 0.13 mT;另一种观察到的PBN加合物H H具有如下hfsc的a N = 1.50 mT和a g H = 0.33 mT。在肾上腺素持续自氧化过程中检测到这些H反应中间体可能解释了儿茶酚胺代谢的生化毒性。这些方法可用于定量和/或表征有机磷中毒后观察到的心脏毒性。
{"title":"ANALYTICAL METHODS TO DETECT THE AUTOOXIDATION OF ADRENOLUTIN AS A STEP IN CATECHOLAMINE METABOLISM","authors":"S. Baskin, George S Behonick, R. J. Schafer, M. Novak, C. Arroyo","doi":"10.1080/107691800317283699","DOIUrl":"https://doi.org/10.1080/107691800317283699","url":null,"abstract":"The acute hemodynamic effects of organophosphate (OP) intoxication include positive chronotropic and inotropic changes along with increases in intraventricular pressure and coronary blood flow. These observations are consistent with an enhanced sympathetic tone that correlates neurogenic cardiomyopathy to adrenergic overactivity and subsequent, focal catecholamine (CA) release and cellular oxidative stress. Several mechanisms have been proposed to explain the cardiotoxicity associated with elevated CA concentrations. However, it is suggested that the oxidative metabolites of CA's, rather than (or in addition to) the parent CA's per se, may initiate or be in part responsible for the cardiotoxicity. The chromatographic profile of adrenochrome (1) and adrenolutin (2) (Figure 1) are described in this study in an isocratic, reverse phase HPLC method using UV/VIS and electrochemical (EC) detection. The aqueous adrenochrome standard shows a retention time of 1.9 minutes under employed conditions. Furthermore, using a flow rate of 0.6 mL/min and a UV/VIS detector set at a wavelength of 490 nm, several chromatographic peaks were detected, indicative of different species after injection of the aqueous adrenolutin standard. A similar multiple peak chromatographic profile was observed with EC detection. We hypothesized from the literature and observed complexity of the chromatogram (i.e. multiple intermediate species of the adrenolutin) that adrenolutin is being autooxidized over time. Based upon EPR spin trapping, we found the generation of a carbon-centered radical at the C-2 position that will interact with oxygen to give an intermediate peroxy radical. This may be eventually transformed to 5,6-dihydroxy-1-methyl-2,3-indoledione. The production of these proposed carbon- and oxygen-centered radicals in the autooxidation of adrenolutin was confirmed by spin trapping experiments using the spin trap, f -phenyl N-tert-butyl nitrone (PBN). When adrenolutin is dissolved in water at neutral pH in the presence of PBN, two different EPR spectra of PBN adducts are obtained. One observed PBN adduct has hyperfine splitting constants (hfsc's) of a N = 1.54 mT, a g H = 0.40 mT, and a n H = 0.13 mT; the other observed PBN adduct H H has the following hfsc's a N = 1.50 mT and a g H = 0.33 mT. The detection of these H reactive intermediates during the continued autooxidation of adrenolutin may account for the biochemical toxicity of catecholamine metabolism. These methods may allow for the quantification and/or characterization of the cardiotoxicity observed after organophosphate (OP) intoxication.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76696312","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 : 2000-10-01DOI: 10.1080/107691800317283671
F. Vargas, G. Fraile, M. Velásquez
By means of a sensitive chemiluminescence's method, toxicity of fenofibric acid was demonstrated on respiratory burst of UVA-irradiated peripheral blood polymorphonuclear cells (PMNs). Through this method, it was possible detect such phototoxic effect at a minor concentration of fenofibric acid as compared with those previously reported in photohemolysis test. This effect was not related with losses of cell viability because PMNs did not lose its capabilities for excluding the trypan blue dye, when irradiated in presence of drug. In order to explain the results obtained in presence of scavengers of different reactive oxygen species, it was proposed a singlet oxygen-mediated (type II) mechanism of photosensitization and/or through formation of toxic photoproducts.
{"title":"DETERMINATION OF THE PHOTOTOXICITY OF FENOFIBRIC ACID BY A SENSITIVE IN VITRO TEST ON POLYMORPHONUCLEAR CELLS","authors":"F. Vargas, G. Fraile, M. Velásquez","doi":"10.1080/107691800317283671","DOIUrl":"https://doi.org/10.1080/107691800317283671","url":null,"abstract":"By means of a sensitive chemiluminescence's method, toxicity of fenofibric acid was demonstrated on respiratory burst of UVA-irradiated peripheral blood polymorphonuclear cells (PMNs). Through this method, it was possible detect such phototoxic effect at a minor concentration of fenofibric acid as compared with those previously reported in photohemolysis test. This effect was not related with losses of cell viability because PMNs did not lose its capabilities for excluding the trypan blue dye, when irradiated in presence of drug. In order to explain the results obtained in presence of scavengers of different reactive oxygen species, it was proposed a singlet oxygen-mediated (type II) mechanism of photosensitization and/or through formation of toxic photoproducts.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84207680","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 : 2000-07-01DOI: 10.1080/107691800300119356
S. Chattopadhyay, M. Misro, S. Pal, J. Debnath, D. Ghosh
Ovarian, uterine, vaginal weights, and ovarian steroidogenic enzyme activities, along with plasma levels of gonadotrophins and estrogen, were measured in diestrous phase of mature Wistar-strain albino rats following subchronic treatment with Na-arsenite at the dose available in drinking water found in wide areas of West Bengal in India. A signicant reduction in plasma levels of LH, FSH, and estradiol, with signicant diminution in the activities of 15-3 ̄ , 17 ̄-HSD followed by a low level of ovarian and uterine peroxidase activity, were observed in Na-arsenite–treated rats at 0.4 ppm/rat/day for 28 days (7 estrous cycles) in comparison to control. This duration of treatment also exhibited weight loss of the above-mentioned organs, with prolonged diestrous phase followed by a high accumulation of arsenic in plasma and in those organs in contrast to controls. Supplementation of ®-tocopherol succinate at 200 mg/kg body weight/rat/day for 28 days with arsenic treatment minimized the gonadal weight loss signicantly and restored the activities of ovarian steroidogenic enzymes as well as ovarian and uterine peroxidase at control level. Not only that, this vitamin also elevated the plasma levels of LH, FSH, and estradiol compared with arsenic-treated rats. Vaginal smear showed normal cyclic changes of estrous in ®-tocopherol succinate supplemented arsenic-treated rats, though arsenic levels in plasma and gonadal tissue remained unaltered in comparison to arsenic-treated rats. Thus, our experiments indicate the signicant protective action of ®-tocopherol succinate on the above-mentioned parameters in arsenic-treated rats.
{"title":"SUPPLEMENTARY EFFECT OF a-TOCOPHEROL SUCCINATE (VITAMIN E) ON SODIUM ARSENITE-INDUCED OVARIAN STEROIDOGENIC FUNCTION AND PLASMA LEVELS OF GONADOTROPHINS IN MATURE ALBINO RATS","authors":"S. Chattopadhyay, M. Misro, S. Pal, J. Debnath, D. Ghosh","doi":"10.1080/107691800300119356","DOIUrl":"https://doi.org/10.1080/107691800300119356","url":null,"abstract":"Ovarian, uterine, vaginal weights, and ovarian steroidogenic enzyme activities, along with plasma levels of gonadotrophins and estrogen, were measured in diestrous phase of mature Wistar-strain albino rats following subchronic treatment with Na-arsenite at the dose available in drinking water found in wide areas of West Bengal in India. A signicant reduction in plasma levels of LH, FSH, and estradiol, with signicant diminution in the activities of 15-3 ̄ , 17 ̄-HSD followed by a low level of ovarian and uterine peroxidase activity, were observed in Na-arsenite–treated rats at 0.4 ppm/rat/day for 28 days (7 estrous cycles) in comparison to control. This duration of treatment also exhibited weight loss of the above-mentioned organs, with prolonged diestrous phase followed by a high accumulation of arsenic in plasma and in those organs in contrast to controls. Supplementation of ®-tocopherol succinate at 200 mg/kg body weight/rat/day for 28 days with arsenic treatment minimized the gonadal weight loss signicantly and restored the activities of ovarian steroidogenic enzymes as well as ovarian and uterine peroxidase at control level. Not only that, this vitamin also elevated the plasma levels of LH, FSH, and estradiol compared with arsenic-treated rats. Vaginal smear showed normal cyclic changes of estrous in ®-tocopherol succinate supplemented arsenic-treated rats, though arsenic levels in plasma and gonadal tissue remained unaltered in comparison to arsenic-treated rats. Thus, our experiments indicate the signicant protective action of ®-tocopherol succinate on the above-mentioned parameters in arsenic-treated rats.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76351502","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 : 2000-07-01DOI: 10.1080/107691800300119374
E. Novelli, Y. S. Diniz, T. Machado, V. Proença, T. Tibiriçá, L. Faine, B. Ribas, J. A. Almeida
The incidence of cardiovascular disease has increased in the general population, and cardiac damage is indicated as one important cause of mortality. In addition, pollution and metal exposure have increased in recent years. For this reason, toxic effects of metals, such as nickel, and the irrelation to cardiac damage should be urgently established. Although free radical-mediated cellular damage and reactive oxygen species have been theorized as contributing to the nickel mechanism of toxicity, recent investigations have established that free radicals may be important contributors to cardiac dysfunction. However,there is little information on the effect of nickel exposure on markers of oxidative stress in cardiac tissue. Nickel exposure (Ni2+ 100 mg L-1 from NiSO4) significantly increased lipoperoxide and total lipid concentrations in cardiac tissue. We also observed increased serum levels of cholesterol(59%), lactate dehydrogenase (LDH-64%), and alanine transaminase (ALT-30%) in study animals. The biochemical parameters recovered to the control values with tocopherol intake (0.2 mg 200 g-1). Vitamin E alone significantly decreased the lipoperoxide concentration and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the heart. Since no alterations were observed in catalase and GSH-Px activities by nickel exposure while SOD activities were decreased, we conclude that superoxide radical (O2 -) generated by nickel exposure is of primary importance in the pathogenesis of cardiac damage. Tocopherol, by its antioxidant activity, decreased the toxic effects of nickel exposure on heart of rats.
{"title":"TOXIC MECHANISM OF NICKEL EXPOSURE ON CARDIAC TISSUE","authors":"E. Novelli, Y. S. Diniz, T. Machado, V. Proença, T. Tibiriçá, L. Faine, B. Ribas, J. A. Almeida","doi":"10.1080/107691800300119374","DOIUrl":"https://doi.org/10.1080/107691800300119374","url":null,"abstract":"The incidence of cardiovascular disease has increased in the general population, and cardiac damage is indicated as one important cause of mortality. In addition, pollution and metal exposure have increased in recent years. For this reason, toxic effects of metals, such as nickel, and the irrelation to cardiac damage should be urgently established. Although free radical-mediated cellular damage and reactive oxygen species have been theorized as contributing to the nickel mechanism of toxicity, recent investigations have established that free radicals may be important contributors to cardiac dysfunction. However,there is little information on the effect of nickel exposure on markers of oxidative stress in cardiac tissue. Nickel exposure (Ni2+ 100 mg L-1 from NiSO4) significantly increased lipoperoxide and total lipid concentrations in cardiac tissue. We also observed increased serum levels of cholesterol(59%), lactate dehydrogenase (LDH-64%), and alanine transaminase (ALT-30%) in study animals. The biochemical parameters recovered to the control values with tocopherol intake (0.2 mg 200 g-1). Vitamin E alone significantly decreased the lipoperoxide concentration and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the heart. Since no alterations were observed in catalase and GSH-Px activities by nickel exposure while SOD activities were decreased, we conclude that superoxide radical (O2 -) generated by nickel exposure is of primary importance in the pathogenesis of cardiac damage. Tocopherol, by its antioxidant activity, decreased the toxic effects of nickel exposure on heart of rats.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83761902","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 : 2000-07-01DOI: 10.1080/107691800300119365
J. S. Vergnes, B. Ballantyne
The genotoxic potential of 2,4-pentanedione (2,4-PD; CAS No. 123-54-6) was assessed using a battery of in vitro and in vivo tests. In vitro studies showed no mutagenic activity in a Salmonella typhimurium reverse mutation test or in a Chinese Hamster Ovary (CHO) forward gene mutation test (HGPRT locus), either in the absence or in the presence of an Aroclor 1245-induced rat liver S9 metabolic activation system. Increased frequencies of sister chromatid exchanges in cultured CHO cells were observed both in the absence and in the presence of S9 activation. 2,4-PD was highly clastogenic to CHO cells in vitro in the absence, but not in the presence, of S9. 2,4-PD produced significant, doserelated increases in the incidence of micronucleated polychromatic erythrocytes (PCE) in the peripheral blood and bone marrow of Swiss Webster mice after a single intraperitoneal injection. However, there was no significant induction of micronuclei in the bone marrow of Sprague Dawley® rats dosed with 2,4-PD by a single intraperitoneal injection. When rats and mice were exposed to 2,4-PD vapor for 6 hr/day for 5 consecutive days at target concentrations up to 800 ppm, there were no significant exposure-related increases in the incidences of chromosomal aberrations or micronucleated PCE in bone marrow samples taken 24 hr after the 5th day of exposure in either species.
{"title":"2,4-PENTANEDIONE: EVALUATION OF THE GENOTOXIC POTENTIAL IN VITRO AND IN VIVO","authors":"J. S. Vergnes, B. Ballantyne","doi":"10.1080/107691800300119365","DOIUrl":"https://doi.org/10.1080/107691800300119365","url":null,"abstract":"The genotoxic potential of 2,4-pentanedione (2,4-PD; CAS No. 123-54-6) was assessed using a battery of in vitro and in vivo tests. In vitro studies showed no mutagenic activity in a Salmonella typhimurium reverse mutation test or in a Chinese Hamster Ovary (CHO) forward gene mutation test (HGPRT locus), either in the absence or in the presence of an Aroclor 1245-induced rat liver S9 metabolic activation system. Increased frequencies of sister chromatid exchanges in cultured CHO cells were observed both in the absence and in the presence of S9 activation. 2,4-PD was highly clastogenic to CHO cells in vitro in the absence, but not in the presence, of S9. 2,4-PD produced significant, doserelated increases in the incidence of micronucleated polychromatic erythrocytes (PCE) in the peripheral blood and bone marrow of Swiss Webster mice after a single intraperitoneal injection. However, there was no significant induction of micronuclei in the bone marrow of Sprague Dawley® rats dosed with 2,4-PD by a single intraperitoneal injection. When rats and mice were exposed to 2,4-PD vapor for 6 hr/day for 5 consecutive days at target concentrations up to 800 ppm, there were no significant exposure-related increases in the incidences of chromosomal aberrations or micronucleated PCE in bone marrow samples taken 24 hr after the 5th day of exposure in either species.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87942248","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 : 2000-04-01DOI: 10.1080/10769180052008896
I. N. Onwurah, M. Eze
The role of superoxide dismutase (SOD) in the survival of diazotrophic bacteria exemplified by Azotobacter vinelandii in the disposition of crude oil-contaminated environment was investigated. The extent of survival, ranging between 57-64% relative to control, was based on colony-forming units of Azotobacter inocula taken from media contaminated with crude oil (0.5-1.5%, w/v), after plating on nutrient agar. The specific activity of superoxide dismutase in the crude protein extracts from cells harvested from oil-contaminated medium and Fenton reagent-containing mediumin creased by 1.25 and 1.28-fold,respectively, relative to control. These results suggest an induction in SOD enzyme protein as a defense mechanism to protect the exposed bacterial cells from the free radicals/reactive oxygen species generated during the oxidation (co-metabolism) of the petroleum hydrocarbons.
{"title":"SUPEROXIDE DISMUTASE ACTIVITY IN AZOTOBACTER VINELANDII IN THE DISPOSITION OF ENVIRONMENTAL TOXICANTS EXEMPLIFIED BY FENTON REAGENT AND CRUDE OIL","authors":"I. N. Onwurah, M. Eze","doi":"10.1080/10769180052008896","DOIUrl":"https://doi.org/10.1080/10769180052008896","url":null,"abstract":"The role of superoxide dismutase (SOD) in the survival of diazotrophic bacteria exemplified by Azotobacter vinelandii in the disposition of crude oil-contaminated environment was investigated. The extent of survival, ranging between 57-64% relative to control, was based on colony-forming units of Azotobacter inocula taken from media contaminated with crude oil (0.5-1.5%, w/v), after plating on nutrient agar. The specific activity of superoxide dismutase in the crude protein extracts from cells harvested from oil-contaminated medium and Fenton reagent-containing mediumin creased by 1.25 and 1.28-fold,respectively, relative to control. These results suggest an induction in SOD enzyme protein as a defense mechanism to protect the exposed bacterial cells from the free radicals/reactive oxygen species generated during the oxidation (co-metabolism) of the petroleum hydrocarbons.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72838331","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 : 2000-04-01DOI: 10.1080/10769180052008887
A. Bhatia, J. Kaur
Effects of sublethal and subchronic doses of dimethoate (DM), an organophosphorus pesticide, have been studied on hematological and immunological parameters in mice. The results revealed that DM-treated mice showed significant increase in red blood cells (RBC), white blood cells, percent monocytes, and percent basophils, whereas the percent neutrophils was significantly decreased.The antibody titres were higher on day 4 postantigen(sheep RBC/bovine serum albumin [BSA]) inoculation, but suppressed on day 7 and 11 postantigen inoculation in DM-treated mice. However, the three cell-mediated immune parameters-leukocyte migration inhibition (LMI), leukocyte adherence inhibition (LAI), and nitroblue tetrazolium (NBT) reduction-were invariably depressed in DM-treated BSA-immunized mice, whereas the percent LMI and LAI were lower and NBT was higher in the DM-treated SRBC-immunized mice. Our results show that exposure to DM suppresses humoral and cell-mediated immune response, but its effect on macrophage function varies with the immunizing antigen.
{"title":"EVALUATION OF HEMATOLOGICAL AND IMMUNOLOGICAL PARAMETERS IN MICE EXPOSED TO SUBLETHAL AND SUBCHRONIC DOSES OF DIMETHOATE","authors":"A. Bhatia, J. Kaur","doi":"10.1080/10769180052008887","DOIUrl":"https://doi.org/10.1080/10769180052008887","url":null,"abstract":"Effects of sublethal and subchronic doses of dimethoate (DM), an organophosphorus pesticide, have been studied on hematological and immunological parameters in mice. The results revealed that DM-treated mice showed significant increase in red blood cells (RBC), white blood cells, percent monocytes, and percent basophils, whereas the percent neutrophils was significantly decreased.The antibody titres were higher on day 4 postantigen(sheep RBC/bovine serum albumin [BSA]) inoculation, but suppressed on day 7 and 11 postantigen inoculation in DM-treated mice. However, the three cell-mediated immune parameters-leukocyte migration inhibition (LMI), leukocyte adherence inhibition (LAI), and nitroblue tetrazolium (NBT) reduction-were invariably depressed in DM-treated BSA-immunized mice, whereas the percent LMI and LAI were lower and NBT was higher in the DM-treated SRBC-immunized mice. Our results show that exposure to DM suppresses humoral and cell-mediated immune response, but its effect on macrophage function varies with the immunizing antigen.","PeriodicalId":87425,"journal":{"name":"Toxic substance mechanisms","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73597414","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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