Comparative neurotoxicity and pyrrole-forming potential of 2,5-hexanedione and perdeuterio-2,5-hexanedione in the rat
2,5-Hexanedione (2,5-HD), the neurotoxic metabolite of n-hexane, reacts with protein amines to form alkylpyrrole adducts. Pyrrolylation of neurofilament protein may be the initiating molecular event in 2,5-HD neuropathy. The present study compares the neurotoxic and pyrrole-forming potentials of 2,5...
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| Veröffentlicht in: | Toxicol. Appl. Pharmacol.; (United States) 1988, Vol.92 (1), p.75-85 |
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| creator | DeCaprio, Anthony P. Briggs, Robert G. Jackowski, Stephen J. Kim, James C.S. |
| description | 2,5-Hexanedione (2,5-HD), the neurotoxic metabolite of
n-hexane, reacts with protein amines to form alkylpyrrole adducts. Pyrrolylation of neurofilament protein may be the initiating molecular event in 2,5-HD neuropathy. The present study compares the neurotoxic and pyrrole-forming potentials of 2,5-HD with those of perdeuterio-2,5-HD ([D
10]-2,5-HD) in the rat. Due to a requirement for CH bond breaking in the reaction mechanism, the latter derivative was expected to exhibit a primary isotope effect, thus forming the pyrrole at a slower rate.
In vitro studies confirmed that [D
10]-2,5-HD pyrrolylated protein at only one-third of the intial rate seen with native 2,5-HD. Prolonged incubation resulted in similar pyrrole concentrations with both derivatives. Adult, male Wistar rats were administered daily (5 days/week) ip doses of either 3.5 mmol 2,5-HD or [D
10]-2,5-HD/kg/day for 17 days or 2.5 mmol/kg/day for 38 days. At termination, animals administered 2,5-HD and [D
10]-2,5-HD exhibited 27 and 8% body weight loss, respectively. Moderate to severe hindlimb paralysis was present in the 2,5-HD groups while only mild effects were seen in [D
10]-2,5-HD-dosed rats. Neuropathological changes were prominent in spinal cord sections from 2,5-HD-treated animals, while no effects were present in rats given the deuterated derivative. Pyrrole adduct concentrations in serum and axonal cytoskeletal proteins from 2,5-HD-treated animals were two- to threefold higher than in rats given equimolar doses of [D
10]-2,5-HD. Levels of covalent crosslinking of axonal cytoskeletal proteins (assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) appeared to correlate with pyrrole concentrations. Tissue concentrations of each diketone isomer were not significantly different, indicating similar uptake of native and deuterated 2,5-HD. Mass spectrometry revealed rapid back exchange of the terminal (methyl) but not of the internal (methylene) deuteriums of [D
10]-2,5-HD
in vivo. These findings support an absolute requirement for pyrrole formation in γ-diketone neurotoxicity. |
| doi_str_mv | 10.1016/0041-008X(88)90229-3 |
| format | Article |
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n-hexane, reacts with protein amines to form alkylpyrrole adducts. Pyrrolylation of neurofilament protein may be the initiating molecular event in 2,5-HD neuropathy. The present study compares the neurotoxic and pyrrole-forming potentials of 2,5-HD with those of perdeuterio-2,5-HD ([D
10]-2,5-HD) in the rat. Due to a requirement for CH bond breaking in the reaction mechanism, the latter derivative was expected to exhibit a primary isotope effect, thus forming the pyrrole at a slower rate.
In vitro studies confirmed that [D
10]-2,5-HD pyrrolylated protein at only one-third of the intial rate seen with native 2,5-HD. Prolonged incubation resulted in similar pyrrole concentrations with both derivatives. Adult, male Wistar rats were administered daily (5 days/week) ip doses of either 3.5 mmol 2,5-HD or [D
10]-2,5-HD/kg/day for 17 days or 2.5 mmol/kg/day for 38 days. At termination, animals administered 2,5-HD and [D
10]-2,5-HD exhibited 27 and 8% body weight loss, respectively. Moderate to severe hindlimb paralysis was present in the 2,5-HD groups while only mild effects were seen in [D
10]-2,5-HD-dosed rats. Neuropathological changes were prominent in spinal cord sections from 2,5-HD-treated animals, while no effects were present in rats given the deuterated derivative. Pyrrole adduct concentrations in serum and axonal cytoskeletal proteins from 2,5-HD-treated animals were two- to threefold higher than in rats given equimolar doses of [D
10]-2,5-HD. Levels of covalent crosslinking of axonal cytoskeletal proteins (assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) appeared to correlate with pyrrole concentrations. Tissue concentrations of each diketone isomer were not significantly different, indicating similar uptake of native and deuterated 2,5-HD. Mass spectrometry revealed rapid back exchange of the terminal (methyl) but not of the internal (methylene) deuteriums of [D
10]-2,5-HD
in vivo. These findings support an absolute requirement for pyrrole formation in γ-diketone neurotoxicity.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/0041-008X(88)90229-3</identifier><identifier>PMID: 3341029</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>550501 - Metabolism- Tracer Techniques ; 560300 - Chemicals Metabolism & Toxicology ; ADDUCTS ; ALKANES ; ANIMALS ; Ataxia - chemically induced ; Axons - drug effects ; AZOLES ; BASIC BIOLOGICAL SCIENCES ; Biological and medical sciences ; BIOSYNTHESIS ; Body Weight - drug effects ; CENTRAL NERVOUS SYSTEM ; Chemical and industrial products toxicology. Toxic occupational diseases ; CHEMICAL REACTIONS ; COMPARATIVE EVALUATIONS ; CROSS-LINKING ; Cytoskeletal Proteins - analysis ; DEUTERIUM ; Deuterium - adverse effects ; ELECTROPHORESIS ; HETEROCYCLIC COMPOUNDS ; HEXANE ; Hexanones - toxicity ; HYDROCARBONS ; HYDROGEN ISOTOPES ; Injections, Intraperitoneal ; ISOTOPE APPLICATIONS ; ISOTOPE EFFECTS ; ISOTOPES ; KETONES ; Ketones - toxicity ; LIGHT NUCLEI ; Male ; MAMMALS ; Medical sciences ; NERVOUS SYSTEM ; NUCLEI ; ODD-ODD NUCLEI ; ORGANIC COMPOUNDS ; ORGANIC NITROGEN COMPOUNDS ; PATHOLOGICAL CHANGES ; POLYMERIZATION ; PYRROLES ; Pyrroles - analysis ; Pyrroles - biosynthesis ; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT ; RATS ; Rats, Inbred Strains ; RODENTS ; Solvents ; SPINAL CORD ; Spinal Cord - drug effects ; STABLE ISOTOPES ; SYNTHESIS ; TOXICITY ; Toxicology ; TRACER TECHNIQUES ; VERTEBRATES</subject><ispartof>Toxicol. Appl. Pharmacol.; (United States), 1988, Vol.92 (1), p.75-85</ispartof><rights>1988</rights><rights>1988 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-a30bc95ec27f9251d614bd9b2de3f323ec7398a4dd9cdc284ebb50eed0a66d7c3</citedby><cites>FETCH-LOGICAL-c510t-a30bc95ec27f9251d614bd9b2de3f323ec7398a4dd9cdc284ebb50eed0a66d7c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0041-008X(88)90229-3$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,885,3550,4024,27923,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=7716379$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3341029$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/5313520$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>DeCaprio, Anthony P.</creatorcontrib><creatorcontrib>Briggs, Robert G.</creatorcontrib><creatorcontrib>Jackowski, Stephen J.</creatorcontrib><creatorcontrib>Kim, James C.S.</creatorcontrib><creatorcontrib>New York State Department of Health, Albany (USA)</creatorcontrib><title>Comparative neurotoxicity and pyrrole-forming potential of 2,5-hexanedione and perdeuterio-2,5-hexanedione in the rat</title><title>Toxicol. Appl. Pharmacol.; (United States)</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>2,5-Hexanedione (2,5-HD), the neurotoxic metabolite of
n-hexane, reacts with protein amines to form alkylpyrrole adducts. Pyrrolylation of neurofilament protein may be the initiating molecular event in 2,5-HD neuropathy. The present study compares the neurotoxic and pyrrole-forming potentials of 2,5-HD with those of perdeuterio-2,5-HD ([D
10]-2,5-HD) in the rat. Due to a requirement for CH bond breaking in the reaction mechanism, the latter derivative was expected to exhibit a primary isotope effect, thus forming the pyrrole at a slower rate.
In vitro studies confirmed that [D
10]-2,5-HD pyrrolylated protein at only one-third of the intial rate seen with native 2,5-HD. Prolonged incubation resulted in similar pyrrole concentrations with both derivatives. Adult, male Wistar rats were administered daily (5 days/week) ip doses of either 3.5 mmol 2,5-HD or [D
10]-2,5-HD/kg/day for 17 days or 2.5 mmol/kg/day for 38 days. At termination, animals administered 2,5-HD and [D
10]-2,5-HD exhibited 27 and 8% body weight loss, respectively. Moderate to severe hindlimb paralysis was present in the 2,5-HD groups while only mild effects were seen in [D
10]-2,5-HD-dosed rats. Neuropathological changes were prominent in spinal cord sections from 2,5-HD-treated animals, while no effects were present in rats given the deuterated derivative. Pyrrole adduct concentrations in serum and axonal cytoskeletal proteins from 2,5-HD-treated animals were two- to threefold higher than in rats given equimolar doses of [D
10]-2,5-HD. Levels of covalent crosslinking of axonal cytoskeletal proteins (assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) appeared to correlate with pyrrole concentrations. Tissue concentrations of each diketone isomer were not significantly different, indicating similar uptake of native and deuterated 2,5-HD. Mass spectrometry revealed rapid back exchange of the terminal (methyl) but not of the internal (methylene) deuteriums of [D
10]-2,5-HD
in vivo. These findings support an absolute requirement for pyrrole formation in γ-diketone neurotoxicity.</description><subject>550501 - Metabolism- Tracer Techniques</subject><subject>560300 - Chemicals Metabolism & Toxicology</subject><subject>ADDUCTS</subject><subject>ALKANES</subject><subject>ANIMALS</subject><subject>Ataxia - chemically induced</subject><subject>Axons - drug effects</subject><subject>AZOLES</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Biological and medical sciences</subject><subject>BIOSYNTHESIS</subject><subject>Body Weight - drug effects</subject><subject>CENTRAL NERVOUS SYSTEM</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>CHEMICAL REACTIONS</subject><subject>COMPARATIVE EVALUATIONS</subject><subject>CROSS-LINKING</subject><subject>Cytoskeletal Proteins - analysis</subject><subject>DEUTERIUM</subject><subject>Deuterium - adverse effects</subject><subject>ELECTROPHORESIS</subject><subject>HETEROCYCLIC COMPOUNDS</subject><subject>HEXANE</subject><subject>Hexanones - toxicity</subject><subject>HYDROCARBONS</subject><subject>HYDROGEN ISOTOPES</subject><subject>Injections, Intraperitoneal</subject><subject>ISOTOPE APPLICATIONS</subject><subject>ISOTOPE EFFECTS</subject><subject>ISOTOPES</subject><subject>KETONES</subject><subject>Ketones - toxicity</subject><subject>LIGHT NUCLEI</subject><subject>Male</subject><subject>MAMMALS</subject><subject>Medical sciences</subject><subject>NERVOUS SYSTEM</subject><subject>NUCLEI</subject><subject>ODD-ODD NUCLEI</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANIC NITROGEN COMPOUNDS</subject><subject>PATHOLOGICAL CHANGES</subject><subject>POLYMERIZATION</subject><subject>PYRROLES</subject><subject>Pyrroles - analysis</subject><subject>Pyrroles - biosynthesis</subject><subject>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</subject><subject>RATS</subject><subject>Rats, Inbred Strains</subject><subject>RODENTS</subject><subject>Solvents</subject><subject>SPINAL CORD</subject><subject>Spinal Cord - drug effects</subject><subject>STABLE ISOTOPES</subject><subject>SYNTHESIS</subject><subject>TOXICITY</subject><subject>Toxicology</subject><subject>TRACER TECHNIQUES</subject><subject>VERTEBRATES</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1988</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-LFDEQxYMo67j6DRQaWUTBaCXpf7kIMrgqLHhR8BbSSbUT6U7aJL3sfHu77WEOHvaUw_u9StV7hDxn8I4Bq98DlIwCtD9ft-0bCZxLKh6QHQNZUxBCPCS7M_KYPEnpNwDIsmQX5EKIkgGXOzLvwzjpqLO7xcLjHEMOd864fCy0t8V0jDEMSPsQR-d_FVPI6LPTQxH6gr-t6AHvtEfrgsfNgNHinDG6QP_XnS_yAYvls6fkUa-HhM9O7yX5cf3p-_4Lvfn2-ev-4w01FYNMtYDOyAoNb3rJK2ZrVnZWdtyi6AUXaBohW11aK401vC2x6ypAtKDr2jZGXJKX29yQslNpOQvNwQTv0WRVCSYqDgv0aoOmGP7MmLIaXTI4DMviYU6Kla2QkjcLWG6giSGliL2aoht1PCoGaq1ErXmrNW_VtupfJUosthen-XM3oj2bTh0s-tVJ18nooY_aG5fOWNOwWjQr9mHDcAns1mFc70FvlnDjeo4N7v49_gLypqld</recordid><startdate>1988</startdate><enddate>1988</enddate><creator>DeCaprio, Anthony P.</creator><creator>Briggs, Robert G.</creator><creator>Jackowski, Stephen J.</creator><creator>Kim, James C.S.</creator><general>Elsevier Inc</general><general>Elsevier</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>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>OTOTI</scope></search><sort><creationdate>1988</creationdate><title>Comparative neurotoxicity and pyrrole-forming potential of 2,5-hexanedione and perdeuterio-2,5-hexanedione in the rat</title><author>DeCaprio, Anthony P. ; Briggs, Robert G. ; Jackowski, Stephen J. ; Kim, James C.S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-a30bc95ec27f9251d614bd9b2de3f323ec7398a4dd9cdc284ebb50eed0a66d7c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1988</creationdate><topic>550501 - Metabolism- Tracer Techniques</topic><topic>560300 - Chemicals Metabolism & Toxicology</topic><topic>ADDUCTS</topic><topic>ALKANES</topic><topic>ANIMALS</topic><topic>Ataxia - chemically induced</topic><topic>Axons - drug effects</topic><topic>AZOLES</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Biological and medical sciences</topic><topic>BIOSYNTHESIS</topic><topic>Body Weight - drug effects</topic><topic>CENTRAL NERVOUS SYSTEM</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>CHEMICAL REACTIONS</topic><topic>COMPARATIVE EVALUATIONS</topic><topic>CROSS-LINKING</topic><topic>Cytoskeletal Proteins - analysis</topic><topic>DEUTERIUM</topic><topic>Deuterium - adverse effects</topic><topic>ELECTROPHORESIS</topic><topic>HETEROCYCLIC COMPOUNDS</topic><topic>HEXANE</topic><topic>Hexanones - toxicity</topic><topic>HYDROCARBONS</topic><topic>HYDROGEN ISOTOPES</topic><topic>Injections, Intraperitoneal</topic><topic>ISOTOPE APPLICATIONS</topic><topic>ISOTOPE EFFECTS</topic><topic>ISOTOPES</topic><topic>KETONES</topic><topic>Ketones - toxicity</topic><topic>LIGHT NUCLEI</topic><topic>Male</topic><topic>MAMMALS</topic><topic>Medical sciences</topic><topic>NERVOUS SYSTEM</topic><topic>NUCLEI</topic><topic>ODD-ODD NUCLEI</topic><topic>ORGANIC COMPOUNDS</topic><topic>ORGANIC NITROGEN COMPOUNDS</topic><topic>PATHOLOGICAL CHANGES</topic><topic>POLYMERIZATION</topic><topic>PYRROLES</topic><topic>Pyrroles - analysis</topic><topic>Pyrroles - biosynthesis</topic><topic>RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT</topic><topic>RATS</topic><topic>Rats, Inbred Strains</topic><topic>RODENTS</topic><topic>Solvents</topic><topic>SPINAL CORD</topic><topic>Spinal Cord - drug effects</topic><topic>STABLE ISOTOPES</topic><topic>SYNTHESIS</topic><topic>TOXICITY</topic><topic>Toxicology</topic><topic>TRACER TECHNIQUES</topic><topic>VERTEBRATES</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DeCaprio, Anthony P.</creatorcontrib><creatorcontrib>Briggs, Robert G.</creatorcontrib><creatorcontrib>Jackowski, Stephen J.</creatorcontrib><creatorcontrib>Kim, James C.S.</creatorcontrib><creatorcontrib>New York State Department of Health, Albany (USA)</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>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>OSTI.GOV</collection><jtitle>Toxicol. Appl. Pharmacol.; (United States)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DeCaprio, Anthony P.</au><au>Briggs, Robert G.</au><au>Jackowski, Stephen J.</au><au>Kim, James C.S.</au><aucorp>New York State Department of Health, Albany (USA)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative neurotoxicity and pyrrole-forming potential of 2,5-hexanedione and perdeuterio-2,5-hexanedione in the rat</atitle><jtitle>Toxicol. Appl. Pharmacol.; (United States)</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>1988</date><risdate>1988</risdate><volume>92</volume><issue>1</issue><spage>75</spage><epage>85</epage><pages>75-85</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>2,5-Hexanedione (2,5-HD), the neurotoxic metabolite of
n-hexane, reacts with protein amines to form alkylpyrrole adducts. Pyrrolylation of neurofilament protein may be the initiating molecular event in 2,5-HD neuropathy. The present study compares the neurotoxic and pyrrole-forming potentials of 2,5-HD with those of perdeuterio-2,5-HD ([D
10]-2,5-HD) in the rat. Due to a requirement for CH bond breaking in the reaction mechanism, the latter derivative was expected to exhibit a primary isotope effect, thus forming the pyrrole at a slower rate.
In vitro studies confirmed that [D
10]-2,5-HD pyrrolylated protein at only one-third of the intial rate seen with native 2,5-HD. Prolonged incubation resulted in similar pyrrole concentrations with both derivatives. Adult, male Wistar rats were administered daily (5 days/week) ip doses of either 3.5 mmol 2,5-HD or [D
10]-2,5-HD/kg/day for 17 days or 2.5 mmol/kg/day for 38 days. At termination, animals administered 2,5-HD and [D
10]-2,5-HD exhibited 27 and 8% body weight loss, respectively. Moderate to severe hindlimb paralysis was present in the 2,5-HD groups while only mild effects were seen in [D
10]-2,5-HD-dosed rats. Neuropathological changes were prominent in spinal cord sections from 2,5-HD-treated animals, while no effects were present in rats given the deuterated derivative. Pyrrole adduct concentrations in serum and axonal cytoskeletal proteins from 2,5-HD-treated animals were two- to threefold higher than in rats given equimolar doses of [D
10]-2,5-HD. Levels of covalent crosslinking of axonal cytoskeletal proteins (assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) appeared to correlate with pyrrole concentrations. Tissue concentrations of each diketone isomer were not significantly different, indicating similar uptake of native and deuterated 2,5-HD. Mass spectrometry revealed rapid back exchange of the terminal (methyl) but not of the internal (methylene) deuteriums of [D
10]-2,5-HD
in vivo. These findings support an absolute requirement for pyrrole formation in γ-diketone neurotoxicity.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>3341029</pmid><doi>10.1016/0041-008X(88)90229-3</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0041-008X |
| ispartof | Toxicol. Appl. Pharmacol.; (United States), 1988, Vol.92 (1), p.75-85 |
| issn | 0041-008X 1096-0333 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_14839927 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | 550501 - Metabolism- Tracer Techniques 560300 - Chemicals Metabolism & Toxicology ADDUCTS ALKANES ANIMALS Ataxia - chemically induced Axons - drug effects AZOLES BASIC BIOLOGICAL SCIENCES Biological and medical sciences BIOSYNTHESIS Body Weight - drug effects CENTRAL NERVOUS SYSTEM Chemical and industrial products toxicology. Toxic occupational diseases CHEMICAL REACTIONS COMPARATIVE EVALUATIONS CROSS-LINKING Cytoskeletal Proteins - analysis DEUTERIUM Deuterium - adverse effects ELECTROPHORESIS HETEROCYCLIC COMPOUNDS HEXANE Hexanones - toxicity HYDROCARBONS HYDROGEN ISOTOPES Injections, Intraperitoneal ISOTOPE APPLICATIONS ISOTOPE EFFECTS ISOTOPES KETONES Ketones - toxicity LIGHT NUCLEI Male MAMMALS Medical sciences NERVOUS SYSTEM NUCLEI ODD-ODD NUCLEI ORGANIC COMPOUNDS ORGANIC NITROGEN COMPOUNDS PATHOLOGICAL CHANGES POLYMERIZATION PYRROLES Pyrroles - analysis Pyrroles - biosynthesis RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT RATS Rats, Inbred Strains RODENTS Solvents SPINAL CORD Spinal Cord - drug effects STABLE ISOTOPES SYNTHESIS TOXICITY Toxicology TRACER TECHNIQUES VERTEBRATES |
| title | Comparative neurotoxicity and pyrrole-forming potential of 2,5-hexanedione and perdeuterio-2,5-hexanedione in the rat |
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