{"title":"Effect of antidepressant drug on semicarbazide-sensitive amine oxidase (SSAO) in dog brain.","authors":"Toshio Obata, Masahiro Aomine","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The present study examined whether or not other cyclic antidepressants, such as the dicyclic drug zimeldine, the tricyclic drug imipramine, and tetracyclic drug maprotiline, and the noncyclic drug nomifensine, inhibit semicarbazide-sensitive amine oxidase (SSAO) activity in dog brain. After treatment with 100 nM clorgyline and 100 nM deprenyl, all four antidepressant drugs inhibit SSAO activity in dog brain. The most potent of inhibition was observed by imipramine, followed by maprotiline, zimeldine and nomifensine. All four drugs are noncompetitive inhibitor of SSAO in dog brain. We found the tricyclic antidepressant drug imipramine to be the most selective inhibitors of SSAO activity in dog brain, as compared with other type of antidepressant drugs.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 1-6","pages":"3-12"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30091675","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}
{"title":"Effects of 5-ethyl-1-phenyl-2-(1H) pyridone on serum biomarkers of multiorgan dysfunction and mortality in lipopolysaccharide/glactosamine and cecal ligation and puncture models of septic shock in mice.","authors":"Ken J Grattendick, James M Nakashima, Shri N Giri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Septic shock results from a systemic host response to infection, in particular, and is associated with multiorgan dysfunction (MOD). Effective preventive measures against organ failure are essential as it is the cumulative burden of MOD that invariably leads to death. The aim of this study was to determine if a novel compound, 5-ethyl-1-phenyl-2-(1H) pyridone (5-EPP), could decrease the increased serum levels of various biomarkers of MOD in LPS/D-Galactosamine (LPS/D-GalN) and cecal ligation and puncture (CLP) models of septic shock in mice. Treatment with 5-EPP minimized the liver dysfunction as assessed by its ability to decrease the increased serum levels of aminotransferases. It also reduced proinflammatory cytokines such as TNF-alpha, IL-6 and IL-12, and offered complete protection against mortality in LPS/D-GalN model. 5-EPP treatment also offered a significant protection against LPS alone- induced mortality. Pretreatment with 5-EPP minimized the kidney, heart and muscle damage as assessed by its ability to decrease the CLP-induced increases in the serum levels of blood urea nitrogen, creatine kinase, glucose and mortality. Several possible mechanisms for the beneficial effects of 5-EPP in the LPS/D-GalN, LPS alone, and CLP models of septic shock have been discussed. It was concluded from the findings of this study that 5-EPP, a novel pyridone, is a promising candidate for the management of septic shock by offering protection against MOD and mortality clinically seen in septic patients.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 1-6","pages":"27-50"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30091677","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}
{"title":"Effect of antidepressant drug on semicarbazide-sensitive amine oxidase (SSAO) in dog brain.","authors":"Toshio Obata, Masahiro Aomine","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The present study examined whether or not other cyclic antidepressants, such as the dicyclic drug zimeldine, the tricyclic drug imipramine, and tetracyclic drug maprotiline, and the noncyclic drug nomifensine, inhibit semicarbazide-sensitive amine oxidase (SSAO) activity in dog brain. After treatment with 100 nM clorgyline and 100 nM deprenyl, all four antidepressant drugs inhibit SSAO activity in dog brain. The most potent of inhibition was observed by imipramine, followed by maprotiline, zimeldine and nomifensine. All four drugs are noncompetitive inhibitor of SSAO in dog brain. We found the tricyclic antidepressant drug imipramine to be the most selective inhibitors of SSAO activity in dog brain, as compared with other type of antidepressant drugs.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 ","pages":"3-12"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32501028","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}
{"title":"Changes in monoamine oxidase activity in hepatic injury: a review.","authors":"Toshio Obata, Masahiro Aomine","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This review focuses on multiplicity of monoamine oxidase (MAO) activity in rat hepatic injury. MAO play a major role in the metabolism of biogenic amines. Stress such as immobilization stress (IMMO) or cold stress changes the multiple forms of MAO activity in rat liver. Thyroid hormone-inducible MAO inhibitor may play some role in regulating the MAO activity in rat liver. Carcinogen such as dimethylnitrosamine (DEN) might change the proportions of the forms of MAO activity in tumor cells. This compound is selective to and an irreversible inhibitor of MAO-B. These changes may account for the multiplicity of MAO by hepatic injury.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 1-6","pages":"51-63"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30091678","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}
{"title":"Effects of 5-ethyl-1-phenyl-2-(1H) pyridone on serum biomarkers of multiorgan dysfunction and mortality in lipopolysaccharide/galactosamine and cecal ligation and puncture models of septic shock in mice.","authors":"Ken J Grattendick, James M Nakashima, Shri N Giri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Septic shock results from a systemic host response to infection, in particular, and is associated with multiorgan dysfunction (MOD). Effective preventive measures against organ failure are essential as it is the cumulative burden of MOD that invariably leads to death. The aim of this study was to determine if a novel compound, 5-ethyl-1-phenyl-2-(1H) pyridone (5-EPP), could decrease the increased serum levels of various biomarkers of MOD in LPS/D-Galactosamine (LPS/D-GalN) and cecal ligation and puncture (CLP) models of septic shock in mice. Treatment with 5-EPP minimized the liver dysfunction as assessed by its ability to decrease the increased serum levels of aminotransferases. It also reduced proinflammatory cytokines such as TNF-alpha, IL-6 and IL-12, and offered complete protection against mortality in LPS/D-GalN model. 5-EPP treatment also offered a significant protection against LPS alone- induced mortality. Pretreatment with 5-EPP minimized the kidney, heart and muscle damage as assessed by its ability to decrease the CLP-induced increases in the serum levels of blood urea nitrogen, creatine kinase, glucose and mortality. Several possible mechanisms for the beneficial effects of 5-EPP in the LPS/D-GalN, LPS alone, and CLP models of septic shock have been discussed. It was concluded from the findings of this study that 5-EPP, a novel pyridone, is a promising candidate for the management of septic shock by offering protection against MOD and mortality clinically seen in septic patients.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 ","pages":"27-50"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32501030","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}
Kelly W Hall, Carlos Muro-Cacho, Alison Abritis, Giffe T Johnson, Raymond D Harbison
{"title":"Attenuation of bromobenzene-induced hepatotoxicity by poly(ADP-ribose) polymerase inhibitors.","authors":"Kelly W Hall, Carlos Muro-Cacho, Alison Abritis, Giffe T Johnson, Raymond D Harbison","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Inhibitors of the nuclear enzyme poly-(ADP-ribose) polymerase (PARP) have been demonstrated to attenuate pathophysiological conditions associated with toxicant-induced oxidative stress. This investigation evaluates Nicotinamide (NIC), a non-specific PARP inhibitor, and 6(5)-Phenanthridinone (Phen), a specific PARP-1 inhibitor, for their efficacy in blocking or attenuating bromobenzene (BB) induced hepatocellular toxicity. Male ICR mice were treated with an intraperitoneal injection of bromobenzene, followed by concomitant treatment with NIC or with NIC at 0.5, 1 and 2 hours after BB treatment, or with concomitant treatment of Phen at 10 mg/ml, 20 mg/ml, or 40 mg/ml solution concentration. Mice with only BB treatment displayed substantial hepatotoxicity as evidenced by a 3.5-fold increase in serum alanine transferase (ALT) compared to controls. Mice treated with 3 injections of NIC (at 0.5, 1 and 2 hours) after BB treatment demonstrated a 90% reduction in serum ALT at 24 hours after BB treatment (p < 0.05). Mice with concomitant BB and Phen treatment demonstrated a 75% reduction in ALT at 24 hours after treatment (p < 0.05). Histological evaluations of centrilobular hepatic tissue from treated animals confirm findings of reduced hepatotoxicity as indicated by the ALT results in the NIC and Phen treatment groups. Mortality after 7 days was reduced to levels near controls in the NIC and Phen treatment groups. The PARP-1 inhibitors evaluated in this investigation produce clinically significant attenuation of BB-induced liver injury in male ICR mice.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 ","pages":"79-95"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32501033","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}
{"title":"The properties of B-form monoamine oxidase in mitochondria from monkey platelet.","authors":"Toshio Obata, Masahiro Aomine","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 ","pages":"13-26"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32501029","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}
{"title":"Changes in monoamine oxidase activity in hepatic injury: a review.","authors":"Toshio Obata, Masahiro Aomine","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This review focuses on multiplicity of monoamine oxidase (MAO) activity in rat hepatic injury. MAO play a major role in the metabolism of biogenic amines. Stress such as immobilization stress (IMMO) or cold stress changes the multiple forms of MAO activity in rat liver. Thyroid hormone-inducible MAO inhibitor may play some role in regulating the MAO activity in rat liver. Carcinogen such as dimethylnitrosamine (DEN) might change the proportions of the forms of MAO activity in tumor cells. This compound is selective to and an irreversible inhibitor of MAO-B. These changes may account for the multiplicity of MAO by hepatic injury.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 ","pages":"51-63"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32501031","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}
{"title":"The properties of B-form monoamine oxidase in mitochondria from monkey platelet.","authors":"Toshio Obata, Masahiro Aomine","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 1-6","pages":"13-26"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30091676","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}
Kelly W Hall, Carlos Muro-Cacho, Alison Abritis, Giffe T Johnson, Raymond D Harbison
{"title":"Attenuation of bromobenzene-induced hepatotoxicity by poly(ADP-ribose) polymerase inhibitors.","authors":"Kelly W Hall, Carlos Muro-Cacho, Alison Abritis, Giffe T Johnson, Raymond D Harbison","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Inhibitors of the nuclear enzyme poly-(ADP-ribose) polymerase (PARP) have been demonstrated to attenuate pathophysiological conditions associated with toxicant-induced oxidative stress. This investigation evaluates Nicotinamide (NIC), a non-specific PARP inhibitor, and 6(5)-Phenanthridinone (Phen), a specific PARP-1 inhibitor, for their efficacy in blocking or attenuating bromobenzene (BB) induced hepatocellular toxicity. Male ICR mice were treated with an intraperitoneal injection of bromobenzene, followed by concomitant treatment with NIC or with NIC at 0.5, 1 and 2 hours after BB treatment, or with concomitant treatment of Phen at 10 mg/ml, 20 mg/ml, or 40 mg/ml solution concentration. Mice with only BB treatment displayed substantial hepatotoxicity as evidenced by a 3.5-fold increase in serum alanine transferase (ALT) compared to controls. Mice treated with 3 injections of NIC (at 0.5, 1 and 2 hours) after BB treatment demonstrated a 90% reduction in serum ALT at 24 hours after BB treatment (p < 0.05). Mice with concomitant BB and Phen treatment demonstrated a 75% reduction in ALT at 24 hours after treatment (p < 0.05). Histological evaluations of centrilobular hepatic tissue from treated animals confirm findings of reduced hepatotoxicity as indicated by the ALT results in the NIC and Phen treatment groups. Mortality after 7 days was reduced to levels near controls in the NIC and Phen treatment groups. The PARP-1 inhibitors evaluated in this investigation produce clinically significant attenuation of BB-induced liver injury in male ICR mice.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"122-123 1-6","pages":"79-95"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30091679","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}