Cimetidine enhances the hepatoprotective action of N-acetylcysteine in mice treated with toxic doses of paracetamol
Paracetamol, in toxic doses, is associated with extensive liver damage. This represents one of the common causes of morbidity and mortality in drug poisoning cases. This study was undertaken to investigate the possible potentiation of the hepatoprotective action of N-acetylcysteine (NAC) by cimetidi...
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| Veröffentlicht in: | Toxicology (Amsterdam) 1997-09, Vol.121 (3), p.223-228 |
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| creator | Al-Mustafa, Zaki H Al-Ali, Amein K Qaw, Fuad S Abdul-Cader, Ziaudeen |
| description | Paracetamol, in toxic doses, is associated with extensive liver damage. This represents one of the common causes of morbidity and mortality in drug poisoning cases. This study was undertaken to investigate the possible potentiation of the hepatoprotective action of
N-acetylcysteine (NAC) by cimetidine (CMD), an inhibitor of hepatic microsomal oxidative enzymes. The effects of NAC, cimetidine and the two in combination, administered 2 h post-paracetamol dose, on mortality, plasma glutamic oxaloacetic (GOT) and glutamic pyruvic (GPT) transaminase activities and hepatic reduced glutathione (GSH) levels were investigated in mice 24 h after treatment with a single oral dose of paracetamol (400 mg/kg). Both NAC and cimetidine caused a partial improvement of survival rate, plasma GOT and GPT activities. In addition, they prevented the depletion of hepatic GSH contents. However, concomitant administration of NAC and cimetidine produced a 100% survival rate and a marked reduction in plasma GOT and GPT activities to within the normal range, while significantly raising hepatic GSH concentrations to values close to those measured in saline-treated control animals. It is therefore concluded that cimetidine and
N-acetylcysteine may have an additive hepatoprotective action in the treatment of paracetamol overdose. |
| doi_str_mv | 10.1016/S0300-483X(97)00069-3 |
| format | Article |
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N-acetylcysteine (NAC) by cimetidine (CMD), an inhibitor of hepatic microsomal oxidative enzymes. The effects of NAC, cimetidine and the two in combination, administered 2 h post-paracetamol dose, on mortality, plasma glutamic oxaloacetic (GOT) and glutamic pyruvic (GPT) transaminase activities and hepatic reduced glutathione (GSH) levels were investigated in mice 24 h after treatment with a single oral dose of paracetamol (400 mg/kg). Both NAC and cimetidine caused a partial improvement of survival rate, plasma GOT and GPT activities. In addition, they prevented the depletion of hepatic GSH contents. However, concomitant administration of NAC and cimetidine produced a 100% survival rate and a marked reduction in plasma GOT and GPT activities to within the normal range, while significantly raising hepatic GSH concentrations to values close to those measured in saline-treated control animals. It is therefore concluded that cimetidine and
N-acetylcysteine may have an additive hepatoprotective action in the treatment of paracetamol overdose.</description><identifier>ISSN: 0300-483X</identifier><identifier>EISSN: 1879-3185</identifier><identifier>DOI: 10.1016/S0300-483X(97)00069-3</identifier><identifier>PMID: 9231700</identifier><identifier>CODEN: TXICDD</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject><![CDATA[Acetaminophen - administration & dosage ; Acetaminophen - toxicity ; Acetylcysteine - administration & dosage ; Acetylcysteine - pharmacology ; Acetylcysteine - therapeutic use ; Administration, Oral ; Alanine Transaminase - blood ; Analgesics, Non-Narcotic - administration & dosage ; Analgesics, Non-Narcotic - toxicity ; Animals ; Aspartate Aminotransferases - blood ; Biological and medical sciences ; Cimetidine ; Cimetidine - administration & dosage ; Cimetidine - pharmacology ; Cimetidine - therapeutic use ; Drug toxicity and drugs side effects treatment ; Free Radical Scavengers - administration & dosage ; Free Radical Scavengers - pharmacology ; Free Radical Scavengers - therapeutic use ; Glutathione ; Glutathione - metabolism ; Histamine H2 Antagonists - administration & dosage ; Histamine H2 Antagonists - pharmacology ; Histamine H2 Antagonists - therapeutic use ; Liver - drug effects ; Liver - enzymology ; Liver - pathology ; Liver damage ; Liver Diseases - mortality ; Liver Diseases - pathology ; Liver Diseases - prevention & control ; Male ; Medical sciences ; Mice ; Microsomes, Liver - drug effects ; Microsomes, Liver - enzymology ; N-acetylcysteine ; Necrosis ; Paracetamol ; Pharmacology. Drug treatments ; Survival Rate ; Toxicity ; Toxicity: digestive system]]></subject><ispartof>Toxicology (Amsterdam), 1997-09, Vol.121 (3), p.223-228</ispartof><rights>1997 Elsevier Science Ireland Ltd</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-aed1b2da23328448a6db399a84a9b535248102e1fb2dba6cf30b84b9d23463e73</citedby><cites>FETCH-LOGICAL-c472t-aed1b2da23328448a6db399a84a9b535248102e1fb2dba6cf30b84b9d23463e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0300483X97000693$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2760070$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9231700$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Al-Mustafa, Zaki H</creatorcontrib><creatorcontrib>Al-Ali, Amein K</creatorcontrib><creatorcontrib>Qaw, Fuad S</creatorcontrib><creatorcontrib>Abdul-Cader, Ziaudeen</creatorcontrib><title>Cimetidine enhances the hepatoprotective action of N-acetylcysteine in mice treated with toxic doses of paracetamol</title><title>Toxicology (Amsterdam)</title><addtitle>Toxicology</addtitle><description>Paracetamol, in toxic doses, is associated with extensive liver damage. This represents one of the common causes of morbidity and mortality in drug poisoning cases. This study was undertaken to investigate the possible potentiation of the hepatoprotective action of
N-acetylcysteine (NAC) by cimetidine (CMD), an inhibitor of hepatic microsomal oxidative enzymes. The effects of NAC, cimetidine and the two in combination, administered 2 h post-paracetamol dose, on mortality, plasma glutamic oxaloacetic (GOT) and glutamic pyruvic (GPT) transaminase activities and hepatic reduced glutathione (GSH) levels were investigated in mice 24 h after treatment with a single oral dose of paracetamol (400 mg/kg). Both NAC and cimetidine caused a partial improvement of survival rate, plasma GOT and GPT activities. In addition, they prevented the depletion of hepatic GSH contents. However, concomitant administration of NAC and cimetidine produced a 100% survival rate and a marked reduction in plasma GOT and GPT activities to within the normal range, while significantly raising hepatic GSH concentrations to values close to those measured in saline-treated control animals. It is therefore concluded that cimetidine and
N-acetylcysteine may have an additive hepatoprotective action in the treatment of paracetamol overdose.</description><subject>Acetaminophen - administration & dosage</subject><subject>Acetaminophen - toxicity</subject><subject>Acetylcysteine - administration & dosage</subject><subject>Acetylcysteine - pharmacology</subject><subject>Acetylcysteine - therapeutic use</subject><subject>Administration, Oral</subject><subject>Alanine Transaminase - blood</subject><subject>Analgesics, Non-Narcotic - administration & dosage</subject><subject>Analgesics, Non-Narcotic - toxicity</subject><subject>Animals</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Biological and medical sciences</subject><subject>Cimetidine</subject><subject>Cimetidine - administration & dosage</subject><subject>Cimetidine - pharmacology</subject><subject>Cimetidine - therapeutic use</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Free Radical Scavengers - administration & dosage</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Free Radical Scavengers - therapeutic use</subject><subject>Glutathione</subject><subject>Glutathione - metabolism</subject><subject>Histamine H2 Antagonists - administration & dosage</subject><subject>Histamine H2 Antagonists - pharmacology</subject><subject>Histamine H2 Antagonists - therapeutic use</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Liver - pathology</subject><subject>Liver damage</subject><subject>Liver Diseases - mortality</subject><subject>Liver Diseases - pathology</subject><subject>Liver Diseases - prevention & control</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microsomes, Liver - drug effects</subject><subject>Microsomes, Liver - enzymology</subject><subject>N-acetylcysteine</subject><subject>Necrosis</subject><subject>Paracetamol</subject><subject>Pharmacology. Drug treatments</subject><subject>Survival Rate</subject><subject>Toxicity</subject><subject>Toxicity: digestive system</subject><issn>0300-483X</issn><issn>1879-3185</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1r3DAQhkVpSbdJf0JAh1LSg1N9rW2dQljSNhCSQxvoTYylMatiWxtJm3T_feXssteeRjDPO9I8IuScs0vOeP31J5OMVaqVvy9084UxVutKviEL3jblwNvlW7I4Iu_Jh5T-FEhIVZ-QEy0kbxhbkLTyI2bv_IQUpzVMFhPNa6Rr3EAOmxgy2uyfkUIpYaKhp_cVWMy7we5SxjnoJzp6izRHhIyOvvi8pjn89Za6kMrAEtpAnFMwhuGMvOthSPjxUE_J47ebX6sf1d3D99vV9V1lVSNyBeh4JxwIKUWrVAu166TW0CrQ3VIuhWo5E8j7AnVQ216yrlWddvOOEht5Sj7v55YtnraYshl9sjgMMGHYJsNrppVisoDLPWhjSClibzbRjxB3hjMzyzavss1s0ujGvMo2c-78cMG2G9EdUwe7pf_p0IdkYehj0evTERNNzVgzY1d7DIuMZ4_RJOux_ITzscg3Lvj_POQfYLCdcQ</recordid><startdate>19970905</startdate><enddate>19970905</enddate><creator>Al-Mustafa, Zaki H</creator><creator>Al-Ali, Amein K</creator><creator>Qaw, Fuad S</creator><creator>Abdul-Cader, Ziaudeen</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>19970905</creationdate><title>Cimetidine enhances the hepatoprotective action of N-acetylcysteine in mice treated with toxic doses of paracetamol</title><author>Al-Mustafa, Zaki H ; Al-Ali, Amein K ; Qaw, Fuad S ; Abdul-Cader, Ziaudeen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-aed1b2da23328448a6db399a84a9b535248102e1fb2dba6cf30b84b9d23463e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Acetaminophen - administration & dosage</topic><topic>Acetaminophen - toxicity</topic><topic>Acetylcysteine - administration & dosage</topic><topic>Acetylcysteine - pharmacology</topic><topic>Acetylcysteine - therapeutic use</topic><topic>Administration, Oral</topic><topic>Alanine Transaminase - blood</topic><topic>Analgesics, Non-Narcotic - administration & dosage</topic><topic>Analgesics, Non-Narcotic - toxicity</topic><topic>Animals</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Biological and medical sciences</topic><topic>Cimetidine</topic><topic>Cimetidine - administration & dosage</topic><topic>Cimetidine - pharmacology</topic><topic>Cimetidine - therapeutic use</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Free Radical Scavengers - administration & dosage</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Free Radical Scavengers - therapeutic use</topic><topic>Glutathione</topic><topic>Glutathione - metabolism</topic><topic>Histamine H2 Antagonists - administration & dosage</topic><topic>Histamine H2 Antagonists - pharmacology</topic><topic>Histamine H2 Antagonists - therapeutic use</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Liver - pathology</topic><topic>Liver damage</topic><topic>Liver Diseases - mortality</topic><topic>Liver Diseases - pathology</topic><topic>Liver Diseases - prevention & control</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Microsomes, Liver - drug effects</topic><topic>Microsomes, Liver - enzymology</topic><topic>N-acetylcysteine</topic><topic>Necrosis</topic><topic>Paracetamol</topic><topic>Pharmacology. Drug treatments</topic><topic>Survival Rate</topic><topic>Toxicity</topic><topic>Toxicity: digestive system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Al-Mustafa, Zaki H</creatorcontrib><creatorcontrib>Al-Ali, Amein K</creatorcontrib><creatorcontrib>Qaw, Fuad S</creatorcontrib><creatorcontrib>Abdul-Cader, Ziaudeen</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Toxicology (Amsterdam)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Al-Mustafa, Zaki H</au><au>Al-Ali, Amein K</au><au>Qaw, Fuad S</au><au>Abdul-Cader, Ziaudeen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cimetidine enhances the hepatoprotective action of N-acetylcysteine in mice treated with toxic doses of paracetamol</atitle><jtitle>Toxicology (Amsterdam)</jtitle><addtitle>Toxicology</addtitle><date>1997-09-05</date><risdate>1997</risdate><volume>121</volume><issue>3</issue><spage>223</spage><epage>228</epage><pages>223-228</pages><issn>0300-483X</issn><eissn>1879-3185</eissn><coden>TXICDD</coden><abstract>Paracetamol, in toxic doses, is associated with extensive liver damage. This represents one of the common causes of morbidity and mortality in drug poisoning cases. This study was undertaken to investigate the possible potentiation of the hepatoprotective action of
N-acetylcysteine (NAC) by cimetidine (CMD), an inhibitor of hepatic microsomal oxidative enzymes. The effects of NAC, cimetidine and the two in combination, administered 2 h post-paracetamol dose, on mortality, plasma glutamic oxaloacetic (GOT) and glutamic pyruvic (GPT) transaminase activities and hepatic reduced glutathione (GSH) levels were investigated in mice 24 h after treatment with a single oral dose of paracetamol (400 mg/kg). Both NAC and cimetidine caused a partial improvement of survival rate, plasma GOT and GPT activities. In addition, they prevented the depletion of hepatic GSH contents. However, concomitant administration of NAC and cimetidine produced a 100% survival rate and a marked reduction in plasma GOT and GPT activities to within the normal range, while significantly raising hepatic GSH concentrations to values close to those measured in saline-treated control animals. It is therefore concluded that cimetidine and
N-acetylcysteine may have an additive hepatoprotective action in the treatment of paracetamol overdose.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>9231700</pmid><doi>10.1016/S0300-483X(97)00069-3</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Toxicology (Amsterdam), 1997-09, Vol.121 (3), p.223-228 |
| issn | 0300-483X 1879-3185 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Acetaminophen - administration & dosage Acetaminophen - toxicity Acetylcysteine - administration & dosage Acetylcysteine - pharmacology Acetylcysteine - therapeutic use Administration, Oral Alanine Transaminase - blood Analgesics, Non-Narcotic - administration & dosage Analgesics, Non-Narcotic - toxicity Animals Aspartate Aminotransferases - blood Biological and medical sciences Cimetidine Cimetidine - administration & dosage Cimetidine - pharmacology Cimetidine - therapeutic use Drug toxicity and drugs side effects treatment Free Radical Scavengers - administration & dosage Free Radical Scavengers - pharmacology Free Radical Scavengers - therapeutic use Glutathione Glutathione - metabolism Histamine H2 Antagonists - administration & dosage Histamine H2 Antagonists - pharmacology Histamine H2 Antagonists - therapeutic use Liver - drug effects Liver - enzymology Liver - pathology Liver damage Liver Diseases - mortality Liver Diseases - pathology Liver Diseases - prevention & control Male Medical sciences Mice Microsomes, Liver - drug effects Microsomes, Liver - enzymology N-acetylcysteine Necrosis Paracetamol Pharmacology. Drug treatments Survival Rate Toxicity Toxicity: digestive system |
| title | Cimetidine enhances the hepatoprotective action of N-acetylcysteine in mice treated with toxic doses of paracetamol |
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