CIDeRplusGeneral Information:
| Id: | 3,884 |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance Lipodystrophy |
| Rattus norvegicus | |
| male | |
| Fischer 344 rat | |
| article | |
| Reference: | Ohta T et al.(2009) Untargeted metabolomic profiling as an evaluative tool of fenofibrate-induced toxicology in Fischer 344 male rats Toxicol Pathol 37: 521-535 [PMID: 19458390] |
Interaction Information:
| Comment | A dose of 300 mg/kg/day of fenofibrate was used in this study to induce liver toxicology. Under this dose, the liver was notably enlarged, and the relative weights for liver and kidney increased significantly with time, reaching 2.4- and 1.2-fold, respectively, at day 14. Grossly, the liver was abnormally brown on day 14. Consistent with these findings, hepatocellular hypertrophy and eosinophilia were histopathologically observed on both day 2 and day 14, with more apparent changes on day 14. Also, an increase in the number of mitotic figures was observed on day 2 and day 14 and hepatocyte proliferation was also detectable. Finally, possibly indicating liver injury was slight single-cell necrosis for hepatocytes (although only in 1 of 6 rats). Despite the elevated kidney weight, no noteworthy microscopic findings were observed in the kidneys at day 14. Therefore, the selected dose induced expected liver histological and pathological changes. |
|
Formal Description Interaction-ID: 39160 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | A dose of 300 mg/kg/day of fenofibrate was used in this study to induce liver toxicology. Under this dose, the liver was notably enlarged, and the relative weights for liver and kidney increased significantly with time, reaching 2.4- and 1.2-fold, respectively, at day 14. Grossly, the liver was abnormally brown on day 14. Consistent with these findings, hepatocellular hypertrophy and eosinophilia were histopathologically observed on both day 2 and day 14, with more apparent changes on day 14. Also, an increase in the number of mitotic figures was observed on day 2 and day 14 and hepatocyte proliferation was also detectable. Finally, possibly indicating liver injury was slight single-cell necrosis for hepatocytes (although only in 1 of 6 rats). Despite the elevated kidney weight, no noteworthy microscopic findings were observed in the kidneys at day 14. Therefore, the selected dose induced expected liver histological and pathological changes. |
|
Formal Description Interaction-ID: 39167 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | A dose of 300 mg/kg/day of fenofibrate was used in this study to induce liver toxicology. Under this dose, the liver was notably enlarged, and the relative weights for liver and kidney increased significantly with time, reaching 2.4- and 1.2-fold, respectively, at day 14. Grossly, the liver was abnormally brown on day 14. Consistent with these findings, hepatocellular hypertrophy and eosinophilia were histopathologically observed on both day 2 and day 14, with more apparent changes on day 14. Also, an increase in the number of mitotic figures was observed on day 2 and day 14 and hepatocyte proliferation was also detectable. Finally, possibly indicating liver injury was slight single-cell necrosis for hepatocytes (although only in 1 of 6 rats). Despite the elevated kidney weight, no noteworthy microscopic findings were observed in the kidneys at day 14. Therefore, the selected dose induced expected liver histological and pathological changes. |
|
Formal Description Interaction-ID: 39168 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | A dose of 300 mg/kg/day of fenofibrate was used in this study to induce liver toxicology. Under this dose, the liver was notably enlarged, and the relative weights for liver and kidney increased significantly with time, reaching 2.4- and 1.2-fold, respectively, at day 14. Grossly, the liver was abnormally brown on day 14. Consistent with these findings, hepatocellular hypertrophy and eosinophilia were histopathologically observed on both day 2 and day 14, with more apparent changes on day 14. Also, an increase in the number of mitotic figures was observed on day 2 and day 14 and hepatocyte proliferation was also detectable. Finally, possibly indicating liver injury was slight single-cell necrosis for hepatocytes (although only in 1 of 6 rats). Despite the elevated kidney weight, no noteworthy microscopic findings were observed in the kidneys at day 14. Therefore, the selected dose induced expected liver histological and pathological changes. |
|
Formal Description Interaction-ID: 39169 |
drug/chemical compound increases_activity of phenotype |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites involved in lipid metabolism were found to be significantly altered by fenofibrate treatment. The urinary level of carnitine, a metabolite that is essential for the transportation of long chain fatty acid into mitochondria, was decreased approximately fivefold by fenofibrate at both time points. Also, both plasma and urinary acetylcarnitine were reduced. Plasma 3-hydroxybutanoic acid, a ketone body and the end product of fatty acid beta-oxidation, was significantly increased. In addition, the levels of two urinary dicarboxylic acids, suberic acid and adipic acid, typically derived from fatty acid omega-oxidation pathway, were significantly decreased by fenofibrate. Collectively, these changes are consistent with the expected action of fenofibrate in induction of beta-oxidation. |
|
Formal Description Interaction-ID: 39170 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites involved in lipid metabolism were found to be significantly altered by fenofibrate treatment. The urinary level of carnitine, a metabolite that is essential for the transportation of long chain fatty acid into mitochondria, was decreased approximately fivefold by fenofibrate at both time points. Also, both plasma and urinary acetylcarnitine were reduced. Plasma 3-hydroxybutanoic acid, a ketone body and the end product of fatty acid beta-oxidation, was significantly increased. In addition, the levels of two urinary dicarboxylic acids, suberic acid and adipic acid, typically derived from fatty acid omega-oxidation pathway, were significantly decreased by fenofibrate. Collectively, these changes are consistent with the expected action of fenofibrate in induction of beta-oxidation. |
|
Formal Description Interaction-ID: 39171 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites involved in lipid metabolism were found to be significantly altered by fenofibrate treatment. The urinary level of carnitine, a metabolite that is essential for the transportation of long chain fatty acid into mitochondria, was decreased approximately fivefold by fenofibrate at both time points. Also, both plasma and urinary acetylcarnitine were reduced. Plasma 3-hydroxybutanoic acid, a ketone body and the end product of fatty acid beta-oxidation, was significantly increased. In addition, the levels of two urinary dicarboxylic acids, suberic acid and adipic acid, typically derived from fatty acid omega-oxidation pathway, were significantly decreased by fenofibrate. Collectively, these changes are consistent with the expected action of fenofibrate in induction of beta-oxidation. |
|
Formal Description Interaction-ID: 39172 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites involved in lipid metabolism were found to be significantly altered by fenofibrate treatment. The urinary level of carnitine, a metabolite that is essential for the transportation of long chain fatty acid into mitochondria, was decreased approximately fivefold by fenofibrate at both time points. Also, both plasma and urinary acetylcarnitine were reduced. Plasma 3-hydroxybutanoic acid, a ketone body and the end product of fatty acid beta-oxidation, was significantly increased. In addition, the levels of two urinary dicarboxylic acids, suberic acid and adipic acid, typically derived from fatty acid omega-oxidation pathway, were significantly decreased by fenofibrate. Collectively, these changes are consistent with the expected action of fenofibrate in induction of beta-oxidation. |
|
Formal Description Interaction-ID: 39173 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites involved in lipid metabolism were found to be significantly altered by fenofibrate treatment. The urinary level of carnitine, a metabolite that is essential for the transportation of long chain fatty acid into mitochondria, was decreased approximately fivefold by fenofibrate at both time points. Also, both plasma and urinary acetylcarnitine were reduced. Plasma 3-hydroxybutanoic acid, a ketone body and the end product of fatty acid beta-oxidation, was significantly increased. In addition, the levels of two urinary dicarboxylic acids, suberic acid and adipic acid, typically derived from fatty acid omega-oxidation pathway, were significantly decreased by fenofibrate. Collectively, these changes are consistent with the expected action of fenofibrate in induction of beta-oxidation. |
|
Formal Description Interaction-ID: 39174 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites involved in lipid metabolism were found to be significantly altered by fenofibrate treatment. The urinary level of carnitine, a metabolite that is essential for the transportation of long chain fatty acid into mitochondria, was decreased approximately fivefold by fenofibrate at both time points. Also, both plasma and urinary acetylcarnitine were reduced. Plasma 3-hydroxybutanoic acid, a ketone body and the end product of fatty acid beta-oxidation, was significantly increased. In addition, the levels of two urinary dicarboxylic acids, suberic acid and adipic acid, typically derived from fatty acid omega-oxidation pathway, were significantly decreased by fenofibrate. Collectively, these changes are consistent with the expected action of fenofibrate in induction of beta-oxidation. |
|
Formal Description Interaction-ID: 39175 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The levels of urinary TCA cycle metabolites were significantly reduced by fenofibrate treatment. At both day 2 and day 14, alpha-ketoglutarate was decreased to 10% of the control level. Fumarate and malate were reduced greater than 50 %. Citrate and aconitate also significantly declined at day 14 (although the changes were less apparent at day 2). These results indicated that fenofibrate may cause alterations in the TCA cycle. Consistent with less biochemical flux through the TCA cycle, pyruvate and lactate were 2.5-fold and 1.5-fold greater in the fenofibrate treated group at day 2 compared to control, respectively. |
|
Formal Description Interaction-ID: 39176 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The levels of urinary TCA cycle metabolites were significantly reduced by fenofibrate treatment. At both day 2 and day 14, alpha-ketoglutarate was decreased to 10% of the control level. Fumarate and malate were reduced greater than 50 %. Citrate and aconitate also significantly declined at day 14 (although the changes were less apparent at day 2). These results indicated that fenofibrate may cause alterations in the TCA cycle. Consistent with less biochemical flux through the TCA cycle, pyruvate and lactate were 2.5-fold and 1.5-fold greater in the fenofibrate treated group at day 2 compared to control, respectively. |
|
Formal Description Interaction-ID: 39177 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate or Fumarate |
| Comment | The levels of urinary TCA cycle metabolites were significantly reduced by fenofibrate treatment. At both day 2 and day 14, alpha-ketoglutarate was decreased to 10% of the control level. Fumarate and malate were reduced greater than 50 %. Citrate and aconitate also significantly declined at day 14 (although the changes were less apparent at day 2). These results indicated that fenofibrate may cause alterations in the TCA cycle. Consistent with less biochemical flux through the TCA cycle, pyruvate and lactate were 2.5-fold and 1.5-fold greater in the fenofibrate treated group at day 2 compared to control, respectively. |
|
Formal Description Interaction-ID: 39178 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The levels of urinary TCA cycle metabolites were significantly reduced by fenofibrate treatment. At both day 2 and day 14, alpha-ketoglutarate was decreased to 10% of the control level. Fumarate and malate were reduced greater than 50 %. Citrate and aconitate also significantly declined at day 14 (although the changes were less apparent at day 2). These results indicated that fenofibrate may cause alterations in the TCA cycle. Consistent with less biochemical flux through the TCA cycle, pyruvate and lactate were 2.5-fold and 1.5-fold greater in the fenofibrate treated group at day 2 compared to control, respectively. |
|
Formal Description Interaction-ID: 39179 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The levels of urinary TCA cycle metabolites were significantly reduced by fenofibrate treatment. At both day 2 and day 14, alpha-ketoglutarate was decreased to 10% of the control level. Fumarate and malate were reduced greater than 50 %. Citrate and aconitate also significantly declined at day 14 (although the changes were less apparent at day 2). These results indicated that fenofibrate may cause alterations in the TCA cycle. Consistent with less biochemical flux through the TCA cycle, pyruvate and lactate were 2.5-fold and 1.5-fold greater in the fenofibrate treated group at day 2 compared to control, respectively. |
|
Formal Description Interaction-ID: 39180 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The levels of urinary TCA cycle metabolites were significantly reduced by fenofibrate treatment. At both day 2 and day 14, alpha-ketoglutarate was decreased to 10% of the control level. Fumarate and malate were reduced greater than 50 %. Citrate and aconitate also significantly declined at day 14 (although the changes were less apparent at day 2). These results indicated that fenofibrate may cause alterations in the TCA cycle. Consistent with less biochemical flux through the TCA cycle, pyruvate and lactate were 2.5-fold and 1.5-fold greater in the fenofibrate treated group at day 2 compared to control, respectively. |
|
Formal Description Interaction-ID: 39181 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The levels of urinary TCA cycle metabolites were significantly reduced by fenofibrate treatment. At both day 2 and day 14, alpha-ketoglutarate was decreased to 10% of the control level. Fumarate and malate were reduced greater than 50 %. Citrate and aconitate also significantly declined at day 14 (although the changes were less apparent at day 2). These results indicated that fenofibrate may cause alterations in the TCA cycle. Consistent with less biochemical flux through the TCA cycle, pyruvate and lactate were 2.5-fold and 1.5-fold greater in the fenofibrate treated group at day 2 compared to control, respectively. |
|
Formal Description Interaction-ID: 39182 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The levels of urinary TCA cycle metabolites were significantly reduced by fenofibrate treatment. At both day 2 and day 14, alpha-ketoglutarate was decreased to 10% of the control level. Fumarate and malate were reduced greater than 50 %. Citrate and aconitate also significantly declined at day 14 (although the changes were less apparent at day 2). These results indicated that fenofibrate may cause alterations in the TCA cycle. Consistent with less biochemical flux through the TCA cycle, pyruvate and lactate were 2.5-fold and 1.5-fold greater in the fenofibrate treated group at day 2 compared to control, respectively. |
|
Formal Description Interaction-ID: 39183 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | In addition to lactate and pyruvate, elevations of p-hydroxyphenyllactic acid (HPLA) in the urine and 2-hydroxybutyric acid in the plasma are observed in the fenofibrate-dosed rats. The levels of these metabolites are often used as indicators of lactic acidosis. |
|
Formal Description Interaction-ID: 39184 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | In addition to lactate and pyruvate, elevations of p-hydroxyphenyllactic acid (HPLA) in the urine and 2-hydroxybutyric acid in the plasma are observed in the fenofibrate-dosed rats. The levels of these metabolites are often used as indicators of lactic acidosis. |
|
Formal Description Interaction-ID: 39185 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | In addition to lactate and pyruvate, elevations of p-hydroxyphenyllactic acid (HPLA) in the urine and 2-hydroxybutyric acid in the plasma are observed in the fenofibrate-dosed rats. The levels of these metabolites are often used as indicators of lactic acidosis. |
|
Formal Description Interaction-ID: 39186 |
|
| Comment | In addition to lactate and pyruvate, elevations of p-hydroxyphenyllactic acid (HPLA) in the urine and 2-hydroxybutyric acid in the plasma are observed in the fenofibrate-dosed rats. The levels of these metabolites are often used as indicators of lactic acidosis. |
|
Formal Description Interaction-ID: 39187 |
|
| Comment | The main tryptophan metabolic pathway is the kynurenine pathway. It involves the conversion of tryptophan to kynurenine and ultimately precursors for NAD+ synthesis. Tryptophan can also be degraded to serotonin. Fenofibrate treatment up-regulates the kynurenine pathway. The levels of kynurenine and kynurenate in urine were significantly increased by fenofibrate treatment as early as at day 2. The quinolinate change was not obvious at day 2 but increased as much as twelvefold at day 14. The downstream metabolites of this pathway, nicotinamide, methyl nicotinamide, and 6-hydroxynicotinate were also significantly elevated at day 14. |
|
Formal Description Interaction-ID: 39188 |
drug/chemical compound increases_activity of |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The main tryptophan metabolic pathway is the kynurenine pathway. It involves the conversion of tryptophan to kynurenine and ultimately precursors for NAD+ synthesis. Tryptophan can also be degraded to serotonin. Fenofibrate treatment up-regulates the kynurenine pathway. The levels of kynurenine and kynurenate in urine were significantly increased by fenofibrate treatment as early as at day 2. The quinolinate change was not obvious at day 2 but increased as much as twelvefold at day 14. The downstream metabolites of this pathway, nicotinamide, methyl nicotinamide, and 6-hydroxynicotinate were also significantly elevated at day 14. |
|
Formal Description Interaction-ID: 39198 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The main tryptophan metabolic pathway is the kynurenine pathway. It involves the conversion of tryptophan to kynurenine and ultimately precursors for NAD+ synthesis. Tryptophan can also be degraded to serotonin. Fenofibrate treatment up-regulates the kynurenine pathway. The levels of kynurenine and kynurenate in urine were significantly increased by fenofibrate treatment as early as at day 2. The quinolinate change was not obvious at day 2 but increased as much as twelvefold at day 14. The downstream metabolites of this pathway, nicotinamide, methyl nicotinamide, and 6-hydroxynicotinate were also significantly elevated at day 14. |
|
Formal Description Interaction-ID: 39199 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The main tryptophan metabolic pathway is the kynurenine pathway. It involves the conversion of tryptophan to kynurenine and ultimately precursors for NAD+ synthesis. Tryptophan can also be degraded to serotonin. Fenofibrate treatment up-regulates the kynurenine pathway. The levels of kynurenine and kynurenate in urine were significantly increased by fenofibrate treatment as early as at day 2. The quinolinate change was not obvious at day 2 but increased as much as twelvefold at day 14. The downstream metabolites of this pathway, nicotinamide, methyl nicotinamide, and 6-hydroxynicotinate were also significantly elevated at day 14. |
|
Formal Description Interaction-ID: 39200 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate or Quinolinic acid |
| Comment | The main tryptophan metabolic pathway is the kynurenine pathway. It involves the conversion of tryptophan to kynurenine and ultimately precursors for NAD+ synthesis. Tryptophan can also be degraded to serotonin. Fenofibrate treatment up-regulates the kynurenine pathway. The levels of kynurenine and kynurenate in urine were significantly increased by fenofibrate treatment as early as at day 2. The quinolinate change was not obvious at day 2 but increased as much as twelvefold at day 14. The downstream metabolites of this pathway, nicotinamide, methyl nicotinamide, and 6-hydroxynicotinate were also significantly elevated at day 14. |
|
Formal Description Interaction-ID: 39201 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate or Nicotinamide |
| Comment | The main tryptophan metabolic pathway is the kynurenine pathway. It involves the conversion of tryptophan to kynurenine and ultimately precursors for NAD+ synthesis. Tryptophan can also be degraded to serotonin. Fenofibrate treatment up-regulates the kynurenine pathway. The levels of kynurenine and kynurenate in urine were significantly increased by fenofibrate treatment as early as at day 2. The quinolinate change was not obvious at day 2 but increased as much as twelvefold at day 14. The downstream metabolites of this pathway, nicotinamide, methyl nicotinamide, and 6-hydroxynicotinate were also significantly elevated at day 14. |
|
Formal Description Interaction-ID: 39202 |
drug/chemical compound increases_quantity of drug/chemical compound N-Methylnicotinamide |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The main tryptophan metabolic pathway is the kynurenine pathway. It involves the conversion of tryptophan to kynurenine and ultimately precursors for NAD+ synthesis. Tryptophan can also be degraded to serotonin. Fenofibrate treatment up-regulates the kynurenine pathway. The levels of kynurenine and kynurenate in urine were significantly increased by fenofibrate treatment as early as at day 2. The quinolinate change was not obvious at day 2 but increased as much as twelvefold at day 14. The downstream metabolites of this pathway, nicotinamide, methyl nicotinamide, and 6-hydroxynicotinate were also significantly elevated at day 14. |
|
Formal Description Interaction-ID: 39204 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Fenofibrate treatment down-regulates the conversion of tryptophan to serotonin, at day 14 the urinary levels of serotonin and 5-methoxytryptamine were significantly decreased. |
|
Formal Description Interaction-ID: 39205 |
drug/chemical compound decreases_activity of |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Fenofibrate treatment down-regulates the conversion of tryptophan to serotonin, at day 14 the urinary levels of serotonin and 5-methoxytryptamine were significantly decreased. |
|
Formal Description Interaction-ID: 39206 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Fenofibrate treatment down-regulates the conversion of tryptophan to serotonin, at day 14 the urinary levels of serotonin and 5-methoxytryptamine were significantly decreased. |
|
Formal Description Interaction-ID: 39207 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites associated with oxidative stress were elevated in the fenofibrate-treated group. In particular, components of the glutathione biosynthetic pathways were increased, including gamma-glutamylleucine, gamma-glutamyltyrosine, and 5-oxoproline. Furthermore, allantoin is increased at both day 2 and day 14. Allantoin is produced from uric acid oxidation and proposed to be a marker for oxidative stress. Finally, N,N-dimethylarginine in urine is elevated at both day 2 and 14. This is a posttranslational modification of arginine and is considered a marker of oxidative stress (because the enzyme that catabolizes it, dimethylarginine dimethylamino-hydrolase, is sensitive to oxidizing conditions). |
|
Formal Description Interaction-ID: 39216 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites associated with oxidative stress were elevated in the fenofibrate-treated group. In particular, components of the glutathione biosynthetic pathways were increased, including gamma-glutamylleucine, gamma-glutamyltyrosine, and 5-oxoproline. Furthermore, allantoin is increased at both day 2 and day 14. Allantoin is produced from uric acid oxidation and proposed to be a marker for oxidative stress. Finally, N,N-dimethylarginine in urine is elevated at both day 2 and 14. This is a posttranslational modification of arginine and is considered a marker of oxidative stress (because the enzyme that catabolizes it, dimethylarginine dimethylamino-hydrolase, is sensitive to oxidizing conditions). |
|
Formal Description Interaction-ID: 39219 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites associated with oxidative stress were elevated in the fenofibrate-treated group. In particular, components of the glutathione biosynthetic pathways were increased, including gamma-glutamylleucine, gamma-glutamyltyrosine, and 5-oxoproline. Furthermore, allantoin is increased at both day 2 and day 14. Allantoin is produced from uric acid oxidation and proposed to be a marker for oxidative stress. Finally, N,N-dimethylarginine in urine is elevated at both day 2 and 14. This is a posttranslational modification of arginine and is considered a marker of oxidative stress (because the enzyme that catabolizes it, dimethylarginine dimethylamino-hydrolase, is sensitive to oxidizing conditions). |
|
Formal Description Interaction-ID: 39220 |
drug/chemical compound increases_quantity of drug/chemical compound Glu-Leu |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites associated with oxidative stress were elevated in the fenofibrate-treated group. In particular, components of the glutathione biosynthetic pathways were increased, including gamma-glutamylleucine, gamma-glutamyltyrosine, and 5-oxoproline. Furthermore, allantoin is increased at both day 2 and day 14. Allantoin is produced from uric acid oxidation and proposed to be a marker for oxidative stress. Finally, N,N-dimethylarginine in urine is elevated at both day 2 and 14. This is a posttranslational modification of arginine and is considered a marker of oxidative stress (because the enzyme that catabolizes it, dimethylarginine dimethylamino-hydrolase, is sensitive to oxidizing conditions). |
|
Formal Description Interaction-ID: 39221 |
drug/chemical compound increases_quantity of drug/chemical compound Glu-Tyr |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites associated with oxidative stress were elevated in the fenofibrate-treated group. In particular, components of the glutathione biosynthetic pathways were increased, including gamma-glutamylleucine, gamma-glutamyltyrosine, and 5-oxoproline. Furthermore, allantoin is increased at both day 2 and day 14. Allantoin is produced from uric acid oxidation and proposed to be a marker for oxidative stress. Finally, N,N-dimethylarginine in urine is elevated at both day 2 and 14. This is a posttranslational modification of arginine and is considered a marker of oxidative stress (because the enzyme that catabolizes it, dimethylarginine dimethylamino-hydrolase, is sensitive to oxidizing conditions). |
|
Formal Description Interaction-ID: 39222 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites associated with oxidative stress were elevated in the fenofibrate-treated group. In particular, components of the glutathione biosynthetic pathways were increased, including gamma-glutamylleucine, gamma-glutamyltyrosine, and 5-oxoproline. Furthermore, allantoin is increased at both day 2 and day 14. Allantoin is produced from uric acid oxidation and proposed to be a marker for oxidative stress. Finally, N,N-dimethylarginine in urine is elevated at both day 2 and 14. This is a posttranslational modification of arginine and is considered a marker of oxidative stress (because the enzyme that catabolizes it, dimethylarginine dimethylamino-hydrolase, is sensitive to oxidizing conditions). |
|
Formal Description Interaction-ID: 39223 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Several metabolites associated with oxidative stress were elevated in the fenofibrate-treated group. In particular, components of the glutathione biosynthetic pathways were increased, including gamma-glutamylleucine, gamma-glutamyltyrosine, and 5-oxoproline. Furthermore, allantoin is increased at both day 2 and day 14. Allantoin is produced from uric acid oxidation and proposed to be a marker for oxidative stress. Finally, N,N-dimethylarginine in urine is elevated at both day 2 and 14. This is a posttranslational modification of arginine and is considered a marker of oxidative stress (because the enzyme that catabolizes it, dimethylarginine dimethylamino-hydrolase, is sensitive to oxidizing conditions). |
|
Formal Description Interaction-ID: 39224 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The plasma levels of three bile acids, glycocholic acid, taurocholic acid, and cholic acid, increased significantly by fenofibrate treatment at both time points. In a healthy state, circulating bile acid levels are generally low (for each cycle of enterohepatic circulation, about 95% of bile acids are actively reabsorbed). However, when liver function is compromised, more bile acids can arise in the circulation due to inadequate removal during the enterohepatic circulatory cycle. Fasting serum bile acid levels have been reported as indicators to examine early liver function. Thus, they are considered by some to be more sensitive than many traditional liver enzyme assays. Hence, the elevated levels of bile acids may be an indication that fenofibrate treatment at 300 mg/kg/day resulted in some level of liver malfunction as early as day 2. |
|
Formal Description Interaction-ID: 39225 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate or Cholic acid |
| Comment | The plasma levels of three bile acids, glycocholic acid, taurocholic acid, and cholic acid, increased significantly by fenofibrate treatment at both time points. In a healthy state, circulating bile acid levels are generally low (for each cycle of enterohepatic circulation, about 95% of bile acids are actively reabsorbed). However, when liver function is compromised, more bile acids can arise in the circulation due to inadequate removal during the enterohepatic circulatory cycle. Fasting serum bile acid levels have been reported as indicators to examine early liver function. Thus, they are considered by some to be more sensitive than many traditional liver enzyme assays. Hence, the elevated levels of bile acids may be an indication that fenofibrate treatment at 300 mg/kg/day resulted in some level of liver malfunction as early as day 2. |
|
Formal Description Interaction-ID: 39226 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The plasma levels of three bile acids, glycocholic acid, taurocholic acid, and cholic acid, increased significantly by fenofibrate treatment at both time points. In a healthy state, circulating bile acid levels are generally low (for each cycle of enterohepatic circulation, about 95% of bile acids are actively reabsorbed). However, when liver function is compromised, more bile acids can arise in the circulation due to inadequate removal during the enterohepatic circulatory cycle. Fasting serum bile acid levels have been reported as indicators to examine early liver function. Thus, they are considered by some to be more sensitive than many traditional liver enzyme assays. Hence, the elevated levels of bile acids may be an indication that fenofibrate treatment at 300 mg/kg/day resulted in some level of liver malfunction as early as day 2. |
|
Formal Description Interaction-ID: 39227 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | The plasma levels of three bile acids, glycocholic acid, taurocholic acid, and cholic acid, increased significantly by fenofibrate treatment at both time points. In a healthy state, circulating bile acid levels are generally low (for each cycle of enterohepatic circulation, about 95% of bile acids are actively reabsorbed). However, when liver function is compromised, more bile acids can arise in the circulation due to inadequate removal during the enterohepatic circulatory cycle. Fasting serum bile acid levels have been reported as indicators to examine early liver function. Thus, they are considered by some to be more sensitive than many traditional liver enzyme assays. Hence, the elevated levels of bile acids may be an indication that fenofibrate treatment at 300 mg/kg/day resulted in some level of liver malfunction as early as day 2. |
|
Formal Description Interaction-ID: 39228 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | A 30% reduction was observed in cholesterol levels at day 2 by fenofibrate. Fenofibrate is known to affect cholesterol metabolism. However, at day 14, fenofibrate increased the cholesterol level by 70%. One of the liver's major functions is to capture and metabolize dietary cholesterol in circulation. The increase of cholesterol by fenofibrate at the later time point could likely be due to altered liver function induced by fenofibrate at the high dose of 300 mg/kg/day. |
|
Formal Description Interaction-ID: 39229 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate or Cholesterol |
| Comment | A 30% reduction was observed in cholesterol levels at day 2 by fenofibrate. Fenofibrate is known to affect cholesterol metabolism. However, at day 14, fenofibrate increased the cholesterol level by 70%. One of the liver's major functions is to capture and metabolize dietary cholesterol in circulation. The increase of cholesterol by fenofibrate at the later time point could likely be due to altered liver function induced by fenofibrate at the high dose of 300 mg/kg/day. |
|
Formal Description Interaction-ID: 39230 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate or Cholesterol |
| Comment | Methyl p-hydroxyphenyllactate (MeHPLA) is an important cell growth-regulating agent that inhibits cell growth and proliferation and is easily converted to the free acid, p-hydroxyphenyllactic acid (HPLA), by an esterase in various organs. The level of urinary HPLA was increased by fenofibrate treatment at both day 2 and day 14. |
|
Formal Description Interaction-ID: 39231 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for Fenofibrate |
| Comment | Decrease of urinary putrescine was observed in the fenofibrate treated group at both day 2 and day 14. Because polyamines such as putrescine are generally known to have cancer-promoting effects, the evidence that fenofibrate reduced the level of putrescine was unexpected. However, preliminary targeted metabolite analysis revealed an increase in urinary N1,N12-diacethyspermine and N1, N8-diacethyspemidine. The two diacetyl polyamine derivatives recently have attracted attention as promising tumor markers for diagnosis of cancer. Thus, the decreased putrescine noted in this study may be related to cell proliferation (i.e., the reduction being due to conversion to their diacetyl forms) |
|
Formal Description Interaction-ID: 39232 |
|
| Drugbank entries | Show/Hide entries for Fenofibrate or Putrescine |