Antioxidant activity of vitamin B₆ delays homocysteine-induced atherosclerosis in rats

Abstract

Elevated plasma homocysteine is a risk factor for atherosclerotic disease. In the present study, we have examined whether the oxidative stress due to a low level of vitamin B 6 accelerates the development of homocysteine-induced atherosclerosis in rats. First, the effect of homocysteine thiolactone intake (50 mg/kg per d) on vascular integrity, lipid peroxide concentration, endothelial NO synthase (eNOS) expression and biochemical profiles was examined at day 1, day 21 and day 42 (five rats per group). The histochemical staining of the rat aorta showed no change at day 1 and day 21, but the subendothelial space was observed to be enlarged in rat aorta at day 42 with exposure to homocysteine thiolactone. Expression of eNOS was observed in rat aorta at day 42, but not at day 1 and day 21. Serum lipid peroxide concentration and biochemical profiles including glucose cholesterol and triacylglycerol showed no change at any day. Second, the effect of homocysteine thiolactone intake in the presence and absence of vitamin B 6 on vascular integrity was examined at day 1 and day 14 (five rats per group). Aortic lesions were observed in vitamin B 6 -deficient rat aorta at day 14 but not in vitamin B 6 -supplemented rats. The expression of eNOS was also observed in vitamin B 6 -deficient rat aorta at day 14. Serum lipid concentrations of the vitamin B 6 -deficient group significantly increased compared with concentrations of the vitamin B 6 -supplemented group, though serum concentration of homocysteine did not change between both groups. These results suggest that the oxidative stress caused by a low level of vitamin B 6 accelerates the development of homocysteine-induced atherosclerosis in rats.

Vitamin B6: a challenging link between nutrition and inflammation in CVD

“…Considering the epidemiological evidence of a role of vitamin B 6 in inflammatory-related diseases and the observed relationship with inflammatory markers (11,16,18,79) , it is plausible that vitamin B 6 plays a role in CVD pathogenesis through mechanisms linked to inflammation (Table 4). Therefore, with the knowledge that systemic acute-phase markers are solid and independent risk factors for CAD (80,81) , that inflammation exerts an essential role in all stages of the atherosclerotic process (82) and the possibility that vitamin B 6 has a role in inflammatory processes, several mechanisms were proposed linking low vitamin B 6 and CVD using cell culture studies, animal studies (72) and clinical trials. Animal studies have reported that inflammation reduces circulating and hepatic concentrations of vitamin B 6 .…”

“…Inflammation and vitamin B 6 -related atherogenesis PLP functions as a coenzyme in more than 100 reactions that are involved in the metabolic pathways of neurotransmitters as well as in the metabolism of amino acids, lipids and carbohydrates (72) . PLP also takes part in other significant pathways related to immune function (73) , thrombosis (74,75) and inflammation (17) , all of which are crucial mechanisms in every stage of the atherosclerotic process.…”

Quantification of urinary S- and N-homocysteinylated protein and homocysteine-thiolactone in mice

“…Further, immuno-histochemical studies with ApoE -/-mice show that N-Hcy-protein accumulates in aortic lesions and is enhanced in animals fed a HHcy diet [21]. Treatments with Hcy-thiolactone produce atherosclerotic changes in baboons [22] and rats [23], and cause developmental abnormalities in eyes of chick embryos, including optic lens dislocation, ectopia lentis [24], a diagnostic feature prevalent in CBS-deficient patients [3].…”

Pyridoxamine ameliorates the effects of advanced glycation end products on subtotal nephrectomy induced chronic renal failure rats

“…Deficiency in vitamin B6 is associated with increased homocysteine level and oxidative stress potentially involved in accelerated atherosclerosis (Endo et al, 2006). During Amadori reactions, these highly reactive intermediate carbonyl groups, known as a-dicarbonyls or a-oxoaldehydes that generated from carbonyl stress, are important in the course of all stages and pathways of glycation.…”