title: Toxicological evaluation of advanced glycation end product Nε-(carboxymethyl)lysine: Acute and subacute oral toxicity studies.
abstract: Nε-(carboxymethyl)lysine (CML) as a novel potential noxious compound in various food products has aroused extensive concern in recent years. This study aimed to investigate the oral acute and subacute toxicity of CML in mice as per OECD 420 and 407 guidelines. Acute administration of 2000 and 5000 mg/kg CML did not induce any mortality within 14 days, nevertheless some toxicological symptoms and histopathological changes were observed. The estimated LD50 of CML was >5000 mg/kg. In subacute toxicity test, CML was dosed at 200, 500 and 1000 mg/kg in both genders for 28 days. The body weights reduced which was accompanied with the decrease of food consumptions. Hematology parameters viz. RBC, HGB and MCH showed minor alteration but these were still within normal range. Biochemical analysis of hepatic and renal function markers showed significant elevating in AST, ALT, Cr and BUN etc. Histopathological alterations were observed in lung, liver, kidney and spleen. Subacute toxicity of CML involved oxidative stress caused by reducing antioxidant enzyme (SOD and GSH-Px) activities, and significantly increasing lipid peroxide (MDA) level. In conclusion, CML was unlikely to present an acute hazard, but repeated administration could produce deleterious effects on mice especially inducing liver and kidney damage through oxidative stress.
authors.affiliation: Institute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, Hubei, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, Hubei, China.
authors.forename: Liangqing
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Institute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, Hubei, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, Hubei, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Institute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, Hubei, China.
authors.forename: Shensheng
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Institute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, Hubei, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Qiao
authors.affiliation: Key Laboratory of Food Safety Risk Assessment, Ministry of Health, China National Centre for Food Safety Risk Assessment, Beijing 100021, China.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, Hubei, China. Electronic address: gongwhqg@163.com.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Gong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D005506:Food Contamination; D005511:Food Handling; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D018570:Risk Assessment; D023382:Toxicity Tests, Acute / Q000379:methods*; D059551:Toxicity Tests, Subacute / Q000379:methods*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D015415:Biomarkers; C048496:N(6)-carboxymethyllysine; D008239:Lysine
keywords: Mice; Nε-(carboxymethyl)lysine; Oral acute toxicity; Oxidative stress; Subacute toxicity