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Yoichi Kawashima - One of the best experts on this subject based on the ideXlab platform.
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A single pretreatment with Clofibric Acid attenuates carbon tetrachloride-induced necrosis, but not steatosis, in rat liver.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2020Co-Authors: Yoshihiro Yamakawa, Takaaki Doi, Yoshizumi Naitou, Hiroshi Kawai, Atsushi Mitsumoto, Naomi Kudo, Yoichi KawashimaAbstract:Abstract The present study investigated whether a single pretreatment with Clofibric Acid suppresses liver injury in rats after CCl4 intoxication. Rats received a single pretreatment with Clofibric Acid (100 mg/kg, i.p.) 1 h prior to a CCl4 (1 mL/kg, p.o.) challenge, and were euthanized 24 h after the CCl4 administration. A single pretreatment with Clofibric Acid effectively suppressed increases in the serum aminotransferase activities and the severity of necrosis following the CCl4 challenge, whereas the pretreatment did not protect against CCl4-induced fatty liver. The Clofibric Acid pretreatment did not affect blood concentrations of CCl4 in the early stage after CCl4 dosing, or the level of the CCl4 reaching the liver 1 h after the CCl4 challenge. Moreover, the Clofibric Acid pretreatment did not affect the intensity of the covalent binding of the [14C]CCl4 metabolite to microsomal proteins and lipids. The Clofibric Acid pretreatment did not alter microsomal cytochrome P450 2E1 activity. Based on these results, we conclude that protection against CCl4-induced hepatocellular necrosis by a Clofibric Acid pretreatment does not require its repeated administration, and that a single and brief pre-exposure to Clofibric Acid prior to CCl4 dosing markedly suppresses necrosis without affecting the development and progression of steatosis.
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Inducing Effect of Clofibric Acid on Stearoyl-CoA Desaturase in Intestinal Mucosa of Rats
Lipids, 2014Co-Authors: Tohru Yamazaki, Yoichi Kawashima, Atsushi Mitsumoto, Takeshi Sakamoto, Makiko Kadokura, Yuki Mutoh, Mari Okazaki, Naomi KudoAbstract:Fibrates have been reported to elevate the hepatic proportion of oleic Acid (18:1n-9) through inducing stearoyl-CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of Clofibric Acid on the fatty Acid profile, particularly monounsaturated fatty Acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5 % (w/w) Clofibric Acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n-9 was significantly increased, whereas those of palmitoleic (16:1n-7) and cis -vaccenic (18:1n-7) Acids were not changed. Upon the treatment with Clofibric Acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty Acid elongase (Elovl) 6 was up-regulated, but that of Elovl5 was unaffected. Fat-free diet feeding for 28 days increased the proportions of 16:1n-7 and 18:1n-7, but did not effectively change that of 18:1n-9, in intestinal mucosa. Fat-free diet feeding up-regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by Clofibric Acid and a fat-free diet and suggest that up-regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n-9 in intestinal mucosa.
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Inducing Effect of Clofibric Acid on Stearoyl‐CoA Desaturase in Intestinal Mucosa of Rats
Lipids, 2014Co-Authors: Tohru Yamazaki, Yoichi Kawashima, Atsushi Mitsumoto, Takeshi Sakamoto, Makiko Kadokura, Yuki Mutoh, Mari Okazaki, Naomi KudoAbstract:Fibrates have been reported to elevate the hepatic proportion of oleic Acid (18:1n-9) through inducing stearoyl-CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of Clofibric Acid on the fatty Acid profile, particularly monounsaturated fatty Acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5% (w/w) Clofibric Acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n-9 was significantly increased, whereas those of palmitoleic (16:1n-7) and cis-vaccenic (18:1n-7) Acids were not changed. Upon the treatment with Clofibric Acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty Acid elongase (Elovl) 6 was up-regulated, but that of Elovl5 was unaffected. Fat-free diet feeding for 28 days increased the proportions of 16:1n-7 and 18:1n-7, but did not effectively change that of 18:1n-9, in intestinal mucosa. Fat-free diet feeding up-regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by Clofibric Acid and a fat-free diet and suggest that up-regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n-9 in intestinal mucosa.
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Clofibric Acid Increases the Formation of Oleic Acid in Endoplasmic Reticulum of the Liver of Rats
Journal of pharmacological sciences, 2011Co-Authors: Akihiko Hirose, Atsushi Mitsumoto, Naomi Kudo, Tadashi Tsuda, Tohru Yamazaki, Takeshi Sakamoto, Katsuyoshi Sunaga, Yoichi KawashimaAbstract:Abstract. The effects of 2-(4-chlorophenoxy)-2-methylpropionic Acid (Clofibric Acid) on the formation of oleic Acid (18:1) from stearic Acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [14C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) Clofibric Acid for 7 days; and the distribution of radiolabeled fatty Acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty Acids present in microsomes were significantly increased by the treatment of rats with Clofibric Acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [14C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to Clofibric Acid. The [14C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by Clofibric Acid. These results obtained from the in vivo experiments directly link the findings that Clofibric Acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.
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Stearoyl-CoA desaturase activity is elevated by the suppression of its degradation by Clofibric Acid in the liver of rats.
Journal of pharmacological sciences, 2007Co-Authors: Tomoaki Toyama, Atsushi Mitsumoto, Naomi Kudo, Yasuhide Hibino, Tadashi Tsuda, Yoichi KawashimaAbstract:A mechanism by which fibrates control stearoyl-CoA desaturase (SCD) in the liver was studied. Treatment of rats with 2-(4-chlorophenoxy)-2-methylpropionic Acid (Clofibric Acid) or feeding of a fat-free diet markedly elevated hepatic activity of SCD. Both the treatment with Clofibric Acid and the feeding of the fat-free diet caused an increase in the steady-state level of SCD1 mRNA and enhanced transcriptional rate. The half-lives of SCD for control rats, rats treated with Clofibric Acid rats, and rats fed the fat-free diet were estimated to be 2.0, 3.9, and 1.9 h, respectively. Activity of palmitoyl-CoA chain elongase (PCE) was increased by both Clofibric Acid treatment and feeding of the fat-free diet as was observed with SCD. Steady-state level of rat fatty Acid elongase 2 mRNA was increased by the treatment with Clofibric Acid or feeding of fat-free diet, although the transcriptional rate was not altered. Different from SCD, PCE was highly stable and its half-life was not changed by either Clofibric Acid or fat-free diet. These results strongly suggest that the decreased degradation of SCD is responsible for the increase in its activity in addition to increased transcription of SCD1 in the rats treated with Clofibric Acid.
Naomi Kudo - One of the best experts on this subject based on the ideXlab platform.
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A single pretreatment with Clofibric Acid attenuates carbon tetrachloride-induced necrosis, but not steatosis, in rat liver.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2020Co-Authors: Yoshihiro Yamakawa, Takaaki Doi, Yoshizumi Naitou, Hiroshi Kawai, Atsushi Mitsumoto, Naomi Kudo, Yoichi KawashimaAbstract:Abstract The present study investigated whether a single pretreatment with Clofibric Acid suppresses liver injury in rats after CCl4 intoxication. Rats received a single pretreatment with Clofibric Acid (100 mg/kg, i.p.) 1 h prior to a CCl4 (1 mL/kg, p.o.) challenge, and were euthanized 24 h after the CCl4 administration. A single pretreatment with Clofibric Acid effectively suppressed increases in the serum aminotransferase activities and the severity of necrosis following the CCl4 challenge, whereas the pretreatment did not protect against CCl4-induced fatty liver. The Clofibric Acid pretreatment did not affect blood concentrations of CCl4 in the early stage after CCl4 dosing, or the level of the CCl4 reaching the liver 1 h after the CCl4 challenge. Moreover, the Clofibric Acid pretreatment did not affect the intensity of the covalent binding of the [14C]CCl4 metabolite to microsomal proteins and lipids. The Clofibric Acid pretreatment did not alter microsomal cytochrome P450 2E1 activity. Based on these results, we conclude that protection against CCl4-induced hepatocellular necrosis by a Clofibric Acid pretreatment does not require its repeated administration, and that a single and brief pre-exposure to Clofibric Acid prior to CCl4 dosing markedly suppresses necrosis without affecting the development and progression of steatosis.
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Inducing Effect of Clofibric Acid on Stearoyl-CoA Desaturase in Intestinal Mucosa of Rats
Lipids, 2014Co-Authors: Tohru Yamazaki, Yoichi Kawashima, Atsushi Mitsumoto, Takeshi Sakamoto, Makiko Kadokura, Yuki Mutoh, Mari Okazaki, Naomi KudoAbstract:Fibrates have been reported to elevate the hepatic proportion of oleic Acid (18:1n-9) through inducing stearoyl-CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of Clofibric Acid on the fatty Acid profile, particularly monounsaturated fatty Acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5 % (w/w) Clofibric Acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n-9 was significantly increased, whereas those of palmitoleic (16:1n-7) and cis -vaccenic (18:1n-7) Acids were not changed. Upon the treatment with Clofibric Acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty Acid elongase (Elovl) 6 was up-regulated, but that of Elovl5 was unaffected. Fat-free diet feeding for 28 days increased the proportions of 16:1n-7 and 18:1n-7, but did not effectively change that of 18:1n-9, in intestinal mucosa. Fat-free diet feeding up-regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by Clofibric Acid and a fat-free diet and suggest that up-regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n-9 in intestinal mucosa.
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Inducing Effect of Clofibric Acid on Stearoyl‐CoA Desaturase in Intestinal Mucosa of Rats
Lipids, 2014Co-Authors: Tohru Yamazaki, Yoichi Kawashima, Atsushi Mitsumoto, Takeshi Sakamoto, Makiko Kadokura, Yuki Mutoh, Mari Okazaki, Naomi KudoAbstract:Fibrates have been reported to elevate the hepatic proportion of oleic Acid (18:1n-9) through inducing stearoyl-CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of Clofibric Acid on the fatty Acid profile, particularly monounsaturated fatty Acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5% (w/w) Clofibric Acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n-9 was significantly increased, whereas those of palmitoleic (16:1n-7) and cis-vaccenic (18:1n-7) Acids were not changed. Upon the treatment with Clofibric Acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty Acid elongase (Elovl) 6 was up-regulated, but that of Elovl5 was unaffected. Fat-free diet feeding for 28 days increased the proportions of 16:1n-7 and 18:1n-7, but did not effectively change that of 18:1n-9, in intestinal mucosa. Fat-free diet feeding up-regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by Clofibric Acid and a fat-free diet and suggest that up-regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n-9 in intestinal mucosa.
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Clofibric Acid Increases the Formation of Oleic Acid in Endoplasmic Reticulum of the Liver of Rats
Journal of pharmacological sciences, 2011Co-Authors: Akihiko Hirose, Atsushi Mitsumoto, Naomi Kudo, Tadashi Tsuda, Tohru Yamazaki, Takeshi Sakamoto, Katsuyoshi Sunaga, Yoichi KawashimaAbstract:Abstract. The effects of 2-(4-chlorophenoxy)-2-methylpropionic Acid (Clofibric Acid) on the formation of oleic Acid (18:1) from stearic Acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [14C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) Clofibric Acid for 7 days; and the distribution of radiolabeled fatty Acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty Acids present in microsomes were significantly increased by the treatment of rats with Clofibric Acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [14C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to Clofibric Acid. The [14C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by Clofibric Acid. These results obtained from the in vivo experiments directly link the findings that Clofibric Acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.
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Stearoyl-CoA desaturase activity is elevated by the suppression of its degradation by Clofibric Acid in the liver of rats.
Journal of pharmacological sciences, 2007Co-Authors: Tomoaki Toyama, Atsushi Mitsumoto, Naomi Kudo, Yasuhide Hibino, Tadashi Tsuda, Yoichi KawashimaAbstract:A mechanism by which fibrates control stearoyl-CoA desaturase (SCD) in the liver was studied. Treatment of rats with 2-(4-chlorophenoxy)-2-methylpropionic Acid (Clofibric Acid) or feeding of a fat-free diet markedly elevated hepatic activity of SCD. Both the treatment with Clofibric Acid and the feeding of the fat-free diet caused an increase in the steady-state level of SCD1 mRNA and enhanced transcriptional rate. The half-lives of SCD for control rats, rats treated with Clofibric Acid rats, and rats fed the fat-free diet were estimated to be 2.0, 3.9, and 1.9 h, respectively. Activity of palmitoyl-CoA chain elongase (PCE) was increased by both Clofibric Acid treatment and feeding of the fat-free diet as was observed with SCD. Steady-state level of rat fatty Acid elongase 2 mRNA was increased by the treatment with Clofibric Acid or feeding of fat-free diet, although the transcriptional rate was not altered. Different from SCD, PCE was highly stable and its half-life was not changed by either Clofibric Acid or fat-free diet. These results strongly suggest that the decreased degradation of SCD is responsible for the increase in its activity in addition to increased transcription of SCD1 in the rats treated with Clofibric Acid.
Atsushi Mitsumoto - One of the best experts on this subject based on the ideXlab platform.
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A single pretreatment with Clofibric Acid attenuates carbon tetrachloride-induced necrosis, but not steatosis, in rat liver.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2020Co-Authors: Yoshihiro Yamakawa, Takaaki Doi, Yoshizumi Naitou, Hiroshi Kawai, Atsushi Mitsumoto, Naomi Kudo, Yoichi KawashimaAbstract:Abstract The present study investigated whether a single pretreatment with Clofibric Acid suppresses liver injury in rats after CCl4 intoxication. Rats received a single pretreatment with Clofibric Acid (100 mg/kg, i.p.) 1 h prior to a CCl4 (1 mL/kg, p.o.) challenge, and were euthanized 24 h after the CCl4 administration. A single pretreatment with Clofibric Acid effectively suppressed increases in the serum aminotransferase activities and the severity of necrosis following the CCl4 challenge, whereas the pretreatment did not protect against CCl4-induced fatty liver. The Clofibric Acid pretreatment did not affect blood concentrations of CCl4 in the early stage after CCl4 dosing, or the level of the CCl4 reaching the liver 1 h after the CCl4 challenge. Moreover, the Clofibric Acid pretreatment did not affect the intensity of the covalent binding of the [14C]CCl4 metabolite to microsomal proteins and lipids. The Clofibric Acid pretreatment did not alter microsomal cytochrome P450 2E1 activity. Based on these results, we conclude that protection against CCl4-induced hepatocellular necrosis by a Clofibric Acid pretreatment does not require its repeated administration, and that a single and brief pre-exposure to Clofibric Acid prior to CCl4 dosing markedly suppresses necrosis without affecting the development and progression of steatosis.
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Inducing Effect of Clofibric Acid on Stearoyl-CoA Desaturase in Intestinal Mucosa of Rats
Lipids, 2014Co-Authors: Tohru Yamazaki, Yoichi Kawashima, Atsushi Mitsumoto, Takeshi Sakamoto, Makiko Kadokura, Yuki Mutoh, Mari Okazaki, Naomi KudoAbstract:Fibrates have been reported to elevate the hepatic proportion of oleic Acid (18:1n-9) through inducing stearoyl-CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of Clofibric Acid on the fatty Acid profile, particularly monounsaturated fatty Acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5 % (w/w) Clofibric Acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n-9 was significantly increased, whereas those of palmitoleic (16:1n-7) and cis -vaccenic (18:1n-7) Acids were not changed. Upon the treatment with Clofibric Acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty Acid elongase (Elovl) 6 was up-regulated, but that of Elovl5 was unaffected. Fat-free diet feeding for 28 days increased the proportions of 16:1n-7 and 18:1n-7, but did not effectively change that of 18:1n-9, in intestinal mucosa. Fat-free diet feeding up-regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by Clofibric Acid and a fat-free diet and suggest that up-regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n-9 in intestinal mucosa.
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Inducing Effect of Clofibric Acid on Stearoyl‐CoA Desaturase in Intestinal Mucosa of Rats
Lipids, 2014Co-Authors: Tohru Yamazaki, Yoichi Kawashima, Atsushi Mitsumoto, Takeshi Sakamoto, Makiko Kadokura, Yuki Mutoh, Mari Okazaki, Naomi KudoAbstract:Fibrates have been reported to elevate the hepatic proportion of oleic Acid (18:1n-9) through inducing stearoyl-CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of Clofibric Acid on the fatty Acid profile, particularly monounsaturated fatty Acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5% (w/w) Clofibric Acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n-9 was significantly increased, whereas those of palmitoleic (16:1n-7) and cis-vaccenic (18:1n-7) Acids were not changed. Upon the treatment with Clofibric Acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty Acid elongase (Elovl) 6 was up-regulated, but that of Elovl5 was unaffected. Fat-free diet feeding for 28 days increased the proportions of 16:1n-7 and 18:1n-7, but did not effectively change that of 18:1n-9, in intestinal mucosa. Fat-free diet feeding up-regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by Clofibric Acid and a fat-free diet and suggest that up-regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n-9 in intestinal mucosa.
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Clofibric Acid Increases the Formation of Oleic Acid in Endoplasmic Reticulum of the Liver of Rats
Journal of pharmacological sciences, 2011Co-Authors: Akihiko Hirose, Atsushi Mitsumoto, Naomi Kudo, Tadashi Tsuda, Tohru Yamazaki, Takeshi Sakamoto, Katsuyoshi Sunaga, Yoichi KawashimaAbstract:Abstract. The effects of 2-(4-chlorophenoxy)-2-methylpropionic Acid (Clofibric Acid) on the formation of oleic Acid (18:1) from stearic Acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [14C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) Clofibric Acid for 7 days; and the distribution of radiolabeled fatty Acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty Acids present in microsomes were significantly increased by the treatment of rats with Clofibric Acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [14C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to Clofibric Acid. The [14C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by Clofibric Acid. These results obtained from the in vivo experiments directly link the findings that Clofibric Acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.
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Stearoyl-CoA desaturase activity is elevated by the suppression of its degradation by Clofibric Acid in the liver of rats.
Journal of pharmacological sciences, 2007Co-Authors: Tomoaki Toyama, Atsushi Mitsumoto, Naomi Kudo, Yasuhide Hibino, Tadashi Tsuda, Yoichi KawashimaAbstract:A mechanism by which fibrates control stearoyl-CoA desaturase (SCD) in the liver was studied. Treatment of rats with 2-(4-chlorophenoxy)-2-methylpropionic Acid (Clofibric Acid) or feeding of a fat-free diet markedly elevated hepatic activity of SCD. Both the treatment with Clofibric Acid and the feeding of the fat-free diet caused an increase in the steady-state level of SCD1 mRNA and enhanced transcriptional rate. The half-lives of SCD for control rats, rats treated with Clofibric Acid rats, and rats fed the fat-free diet were estimated to be 2.0, 3.9, and 1.9 h, respectively. Activity of palmitoyl-CoA chain elongase (PCE) was increased by both Clofibric Acid treatment and feeding of the fat-free diet as was observed with SCD. Steady-state level of rat fatty Acid elongase 2 mRNA was increased by the treatment with Clofibric Acid or feeding of fat-free diet, although the transcriptional rate was not altered. Different from SCD, PCE was highly stable and its half-life was not changed by either Clofibric Acid or fat-free diet. These results strongly suggest that the decreased degradation of SCD is responsible for the increase in its activity in addition to increased transcription of SCD1 in the rats treated with Clofibric Acid.
Roberto Andreozzi - One of the best experts on this subject based on the ideXlab platform.
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Removal of organic pollutants from soil : The ozonation of Clofibric Acid in aqueous slurries
Ozone: Science & Engineering, 2006Co-Authors: Marisa Canterino, Roberto Andreozzi, Vincenzo Caprio, Mario Iamarino, Raffaele Marotta, Vincenzo TufanoAbstract:Ozonation is particularly suited for the treatment of recalcitrant soil contaminants. Clofibric Acid, an active metabolite of some blood lipid regulators, was used as a model organic contaminant, and quartzite as a model soil. The measurements performed at different pHs, both in slurries of contaminated soil and in Clofibric Acid aqueous solutions, indicate that a markedly higher TOC removal can be obtained in the slurry mode. Ozonation kinetics in aqueous slurries was also studied in a well-mixed reactor. Suitable mathematical models were used to describe the experiments and to estimate the best values of the unknown parameters.
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Removal of organic pollutants from soil : The ozonation of Clofibric Acid in aqueous slurries
Ozone: Science & Engineering, 2006Co-Authors: Marisa Canterino, Roberto Andreozzi, Vincenzo Caprio, Mario Iamarino, Raffaele Marotta, Vincenzo TufanoAbstract:Ozonation is particularly suited for the treatment of recalcitrant soil contaminants. Clofibric Acid, an active metabolite of some blood lipid regulators, was used as a model organic contaminant, and quartzite as a model soil. The measurements performed at different pHs, both in slurries of contaminated soil and in Clofibric Acid aqueous solutions, indicate that a markedly higher TOC removal can be obtained in the slurry mode. It has been demonstrated that Clofibric Acid can be effectively removed from contaminated soils by a direct treatment with ozone in a slurry system. In terms of TOC removal degree, this treatment appears to be more effective than a two-stage process, which consists of washing the contaminated solid with water and subsequently ozonating the liquid solution obtained. The enhanced reactivity of the contaminated slurry was also evident when measuring the time evolution of the CA-quartzite sandwater system. A simplified model of the slurry system was developed and interesting results were obtained by using at the same time the data collected in three runs at a fixed pH. Work is in progress to improve the results obtained in this investigation by separately studying the release of CA from contaminated quartzite sand to the liquid phase and the ozonation of aqueous CA solutions
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Ozonation and H2O2/UV treatment of Clofibric Acid in water: a kinetic investigation.
Journal of hazardous materials, 2003Co-Authors: Roberto Andreozzi, Vincenzo Caprio, Raffaele Marotta, Anita RadovnikovicAbstract:The presence of pharmaceuticals or their active metabolites in surface and ground waters has been recently reported as mainly due to an incomplete removal of these pollutants in sewage treatment plants (STP). Advanced oxidation processes may represent a suitable tool to reduce environmental release of these species by enhancing the global efficiency of reduction of pharmaceuticals in the municipal sewage plant effluents. The present work aims at assessing the kinetics of abatement from aqueous solutions of Clofibric Acid (a metabolite of the blood lipid regulator clofibrate) which has been found in surface, ground and drinking waters. Ozonation and hydrogen peroxide photolysis are capable of fast removal of this species in aqueous solution, with an almost complete conversion of the organic chlorine content into chloride ions for the investigated reaction conditions. A validation of assessed kinetics at Clofibric Acid concentrations as low as those found in STP effluents is presented for both systems.
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ozonation and h2o2 uv treatment of Clofibric Acid in water a kinetic investigation
Journal of Hazardous Materials, 2003Co-Authors: Roberto Andreozzi, Raffaele Marotta, V Caprio, Anita RadovnikovicAbstract:The presence of pharmaceuticals or their active metabolites in surface and ground waters has been recently reported as mainly due to an incomplete removal of these pollutants in sewage treatment plants (STP). Advanced oxidation processes may represent a suitable tool to reduce environmental release of these species by enhancing the global efficiency of reduction of pharmaceuticals in the municipal sewage plant effluents. The present work aims at assessing the kinetics of abatement from aqueous solutions of Clofibric Acid (a metabolite of the blood lipid regulator clofibrate) which has been found in surface, ground and drinking waters. Ozonation and hydrogen peroxide photolysis are capable of fast removal of this species in aqueous solution, with an almost complete conversion of the organic chlorine content into chloride ions for the investigated reaction conditions. A validation of assessed kinetics at Clofibric Acid concentrations as low as those found in STP effluents is presented for both systems.
Benedetta C. Sallustio - One of the best experts on this subject based on the ideXlab platform.
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UDP-glucuronosyltransferase-dependent bioactivation of Clofibric Acid to a DNA-damaging intermediate in mouse hepatocytes.
Chemico-biological interactions, 2003Co-Authors: Roula Ghaoui, Benedetta C. Sallustio, Philip C. Burcham, Frank FontaineAbstract:Glucuronidation of a number of carboxyl-containing drugs generates reactive acyl glucuronide metabolites. These electrophilic species alkylate cell proteins and may be implicated in the pathogenesis of a number of toxic syndromes seen in patients receiving the parent aglycones. Whether acyl glucuronides also attack nuclear DNA is unknown, although the acyl glucuronide formed from Clofibric Acid was recently found to decrease the transfection efficiency of phage DNA and generate strand breaks in plasmid DNA in vitro. To determine if such a DNA damage occurs within a cellular environment, the comet assay (i.e. single-cell gel electrophoresis) was used to detect DNA lesions in the nuclear genome of isolated mouse hepatocytes cultured with Clofibric Acid. Overnight exposure to 50 μM and higher concentrations of Clofibric Acid produced concentration-dependent increases in the comet areas of hepatocyte nuclei, with 1 mM clofibrate producing a 3.6-fold elevation over controls. These effects closely coincided with culture medium concentrations of the glucuronide metabolite formed from Clofibric Acid, 1-O-β-clofibryl glucuronide. Consistent with a role for glucuronidation in the DNA damage observed, the glucuronidation inhibitor borneol diminished glucuronide formation from 100 μM clofibrate by 98% and returned comet areas to baseline levels. Collectively, these results suggest that the acyl glucuronide formed from Clofibric Acid is capable of migrating from its site of formation within the endoplasmic reticulum to generate strand nicks in nuclear DNA.
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Effects of gemfibrozil and Clofibric Acid on the uptake of taurocholate by isolated rat hepatocytes
Biochemical pharmacology, 1997Co-Authors: Lucia Sabordo, Benedetta C. SallustioAbstract:Clinical use of fibrate hypolipidaemic agents has been associated with an increased incidence of hepatobiliary dysfunction including increased bile lithogenicity, gallstone formation, and cholestasis. The hepatic transport of bile Acids plays an important role in bile formation and flow, and interference with the hepatocellular transport of bile Acids may result in hepatobiliary dysfunction. The aim of this study was to investigate the effects of gemfibrozil and Clofibric Acid on the uptake of taurocholate by rat isolated hepatocytes. In control hepatocyte preparations (N = 5) at 37°, the uptake of taurocholate was described by saturable Michaelis-Menten kinetics with a mean (±SD) Km of 44.1 ± 10.2 μM and Vmax of 62.0 ± 23.0 nmol/106cells/min. In the presence of 200 μM Clofibric Acid, there was no significant change in the kinetics of taurocholate uptake. However, in the presence of 200 μM gemfibrozil there was a statistically significant (P 0.05) in Km (48.5 ± 29.5 μM, N = 5). Gemfibrozil behaved as a non-competitive inhibitor of taurocholate uptake, with a Ki of 144 μM, which is approximately 50 times higher than the unbound gemfibrozil concentrations achieved clinically in humans. Thus, gemfibrozil and Clofibric Acid did not appear to directly alter the hepatic uptake of taurocholate at clinically relevant concentrations.
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In vivo covalent binding of Clofibric Acid to human plasma proteins and rat liver proteins.
Biochemical pharmacology, 1991Co-Authors: Benedetta C. Sallustio, Kathleen M. Knights, Benjamin J. Roberts, Rudolf ZacestAbstract:Abstract Recent studies have shown that acyl-glucuronide conjugates are chemically reactive electrophilic metabolites that can undergo transacylation reactions resulting in intra-molecular rearrangement, hydrolysis and covalent binding of aglycone to albumin both in vitro and in vivo . The hypolipidaemic agent clofibrate is eliminated almost entirely as Clofibric Acid glucuronide in humans and rats. The formation of Clofibric Acid-protein adducts was investigated in 14 patients receiving 0.5–2.0 g day of clofibrate for hypercholesterolaemia, and in liver homogenates from 20 rats administered 280 mg/kg/day of Clofibric Acid for up to 21 days. Total Clofibric Acid concentrations in the patients ranged from 0 to 114 mg L . Covalently bound Clofibric Acid-protein adducts were detected in all patients, even in one subject in whom there was no measurable plasma Clofibric Acid. Concentrations ranged from 2.2 to 53.4 ng mg protein and, in eight patients receiving 1.0 g day of clofibrate, were correlated (P ng mg protein. The covalent binding of drugs to tissue macromolecules has traditionally been associated with toxicity. Further research is required to elucidate the role of acylglucuronide conjugates in the formation of drug-protein adducts and their biological consequences.