title: 4-Hydroxynonenal: A Superior Oxidative Biomarker Compared to Malondialdehyde and Carbonyl Content Induced by Carbon Tetrachloride in Rats.
abstract: Carbon tetrachloride (CCl4), a halogenated substance that generates free radical species during metabolism in vivo, induces hepatotoxicity, produces oxidative DNA damage, and increased levels of protein carbonyl, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE). In this study, Sprague-Dawley rats received single or repeated ip injections of carbon tetrachloride (CCl4), and formation and persistence of carbonyls, MDA, and 4-HNE in plasma were measured using gas chromatography-mass spectrometry. After a single injection of 500 mg/kg CCl4 the in vivo half-lives of MDA and carbonyl content were 1.5 d and 2 d, respectively, while that of 4-HNE was approximately 10 d. Treatment with CCl4 (50, 100, 500, or 1000 mg/kg) dose-dependently increased these oxidative biomarkers in blood. However, formation of protein carbonyls and MDA was less sensitive than 4-HNE to CCl4. Levels of serum glutamic oxaloacetic transaminase (SGOT) and glutamic pyruvic transaminase (SGPT) (hepatotoxicity markers) rose with CCl4 doses. After a single injection (500 mg/kg), the peak level of SGOT was observed after 8 h but SGPT after 24 h. Overall, 4-HNE was more dose-sensitive and showed greater formation subchronically than other biomarkers. Multiple ip treatments with 300 mg CCl4 /kg (d 1, 3, 6, 10, 14, and 21) demonstrated that 4-HNE formation was highest (18-fold, peak/control) and subchronic up to d 21 (last treatment day), unlike other biomarkers. Data suggest that 4-HNE, MDA, and carbonyl content may be useful oxidative biomarkers for exposure to free radical generating halogenated compounds. However, 4-HNE appears to be a more sensitive and sustainable biomarker for toxicological and risk assessments.
authors.affiliation: a Department of Pharmacology and Pharmacogenomics Research Center , College of Medicine, Inje University, 75 Bokgi-ro , Busanjin-gu, Busan 614-735 , South Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: b Department of Biochemistry and Health Science , College of Natural Sciences, Changwon National University , Changwon , Gyeongnam 641-773 , South Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kwack
authors.affiliation: b Department of Biochemistry and Health Science , College of Natural Sciences, Changwon National University , Changwon , Gyeongnam 641-773 , South Korea.
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Yoon
authors.affiliation: b Department of Biochemistry and Health Science , College of Natural Sciences, Changwon National University , Changwon , Gyeongnam 641-773 , South Korea.
authors.forename: Jin Shil
authors.initials: JS
authors.lastname: Choi
authors.affiliation: c Division of Toxicology , College of Pharmacy, Sungkyunkwan University , Suwon , Gyeonggi-Do 440-746 , South Korea.
authors.forename: Byung-Mu
authors.initials: BM
authors.lastname: Lee
mesh_terms: D000447:Aldehydes / Q000097:blood*; D000818:Animals; D015415:Biomarkers; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004784:Environmental Monitoring / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008315:Malondialdehyde / Q000097:blood*; D050050:Protein Carbonylation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D002273:Carcinogens; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; C027576:4-hydroxy-2-nonenal