N-nitrosodiethylamine-induced toxicity in relation to oxidative stress and development of atherosclerosis in hypercholesterolemic diet-fed rabbits

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie Vol. 59; no. 6; pp. 409 - 414
• Main Authors: Mittal, Gaurav, Brar, Apminder Pal Singh, Soni, Giridhar
• Format: Journal Article
• Language: English
• Published: Jena Elsevier GmbH 01.04.2008; Elsevier
• Subjects: Animals; Aorta - drug effects; Aorta - metabolism; Aorta - pathology; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - chemically induced; Atherosclerosis - etiology; Atherosclerosis - metabolism; Atherosclerosis - pathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Coronary Vessels - pathology; Diet, Atherogenic; Diethylnitrosamine - toxicity; Disease Models, Animal; Hypercholesterolemia; Investigative techniques, diagnostic techniques (general aspects); Lipid Metabolism - drug effects; Lipid Peroxidation - drug effects; Lipid Peroxides - blood; Lipids - blood; Liver - drug effects; Liver - metabolism; Male; Medical sciences; N-nitrosodiethylamine (NDEA); Osmotic Fragility - drug effects; Oxidative stress; Oxidative Stress - drug effects; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Rabbit; Rabbits; Tunica Intima - drug effects; Tunica Intima - metabolism; Tunica Intima - pathology; Rabbit; Oxidative stress; Hypercholesterolemia; N-nitrosodiethylamine (NDEA); Atherosclerosis; Nutrition; Toxicity; Metabolic diseases; Cardiovascular disease; Lipids; Hyperlipoproteinemia; Lipoprotein; Lagomorpha; Cholesterol; Feeding; Vascular disease; Vertebrata; Anatomic pathology; Mammalia; Diet; Animal; Development; Dyslipemia
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2007.10.009

N-nitrosodiethylamine (NDEA) is an important carcinogenic nitrosamine frequently present in human environment, besides being a part of the human food chain by virtue of its reported presence in various foodstuffs and beverages. This study was planned to investigate the toxicity of NDEA in relation to the development of atherosclerosis in experimental rabbits. Oral administration of NDEA at 50 mg per day along with hypercholesterolemic diet to rabbits resulted in significant increase in osmotic fragility of erythrocytes as well as increased in vitro lipid peroxidation (LPO) of erythrocytes. The plasma total lipids, cholesterol and glycerides continued to increase during the feeding of hypercholesterolemic diet with or without NDEA. However, after the cessation of hypercholesterolemic diet, decrease in the lipid fractions was relatively less in the experimental group receiving NDEA. Administration of NDEA in the hypercholesterolemic diet did not affect the total lipid content in the liver, although it marginally increased the hepatic cholesterol levels. Histopathological changes in different tissues (heart, aorta and liver) were relatively more severe in experimental rabbits receiving NDEA treatment as compared to the control ones. Our study therefore indicates that oral administration of NDEA results in increased LPO of blood and decreased lipid clearance, which may in turn result in increased degree of atherosclerosis.