Prevention of homocysteine thiolactone induced atherogenesis in rats.
Thioretinamide was conjugated to coenzyme B12 to produce thioretinaco. Thioretinamide, thioretinaco, and coenzyme B12 were injected weekly into Rattus rattus that were also given atherogenic doses of homocysteine thiolactone. The presence or absence of lesions in aorta-intercostal artery junctions was examined. Control rats injected with homocysteine thiolactone (CON-Hcy) had 56.6 +/- 5.8% lesions when compared to 34.8 +/- 3.4% in control rats injected with saline (CON-Sal). Rats that received homocysteine thiolactone injection with thioretinamide (NHTR-Hcy), thioretinaco ((NHTR)2B12-Hcy), and coenzyme B12 (B12-Hcy) had 30.1 +/- 4.2%, 27.5 +/- 3.5%, and 22.8 +/- 3.0% lesions, respectively. These lesion rates were not different from those of rats receiving thioretinamide (NHTR-Sal), thioretinaco ((NHTR)2B12-Sal), and coenzyme B12 (B12-Sal) which were 31.3 +/- 1.8%, 29.8 +/- 3.9%, and 32.0 +/- 4.6%, respectively. In this study the percentage of intercostal artery lesions in rats receiving thioretinamide and homocysteine (NHTR-Hcy), coenzyme B12 and homocysteine (B12-Hcy), and thioretinaco and homocysteine ((NHTR)2/B12-Hcy) were significantly lower, 53.2%, 48.6%, and 40.3% respectively, compared to than that of the control group receiving homocysteine (CON-Hcy). Thioretinaco, thioretinamide, and coenzyme B12 provided protective effects against the atherogen homocysteine thiolactone. A new method for the synthesis of the N-substituted derivative of homocysteine thiolactone, thioretinamide, was also reported.
Kazimir
Michal
M
Laboratory of Physiology, Department of Biology, Baylor University, PO Box 97388, Waco, Texas 76798, USA.
Wilson
F Ray
FR
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000473:pathology; D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D003038:Cobamides / Q000378:metabolism; D005260:Female; D005502:Food; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019946:Propylene Glycol / Q000494:pharmacology; D051381:Rats; D016707:Tissue Fixation; D014212:Tretinoin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D003038:Cobamides; C488375:thioretinaco; D006710:Homocysteine; C053232:N-homocysteine thiolactonyl retinamide; D014212:Tretinoin; D019946:Propylene Glycol; C007957:homocysteine thiolactone; C000913:cobamamide; D014805:Vitamin B 12