Tobacco smoke is a source of toxic reactive glycation products

Abstract

Smokers have a significantly higher risk for developing coronary and cerebrovascular disease than nonsmokers. Advanced glycation end products (AGEs) are reactive, cross-linking moieties that form from the reaction of reducing sugars and the amino groups of proteins, lipids, and nucleic acids. AGEs circulate in high concentrations in the plasma of patients with diabetes or renal insufficiency and have been linked to the accelerated vasculopathy seen in patients with these diseases. Because the curing of tobacco takes place under conditions that could lead to the formation of glycation products, we examined whether tobacco and tobacco smoke could generate these reactive species that would increase AGE formation in vivo. Our findings show that reactive glycation products are present in aqueous extracts of tobacco and in tobacco smoke in a form that can rapidly react with proteins to form AGEs. This reaction can be inhibited by aminoguanidine, a known inhibitor of AGE formation. We have named these glycation products ''glycotoxins.'' Like other known reducing sugars and reactive glycation products, glycotoxins form smoke, react with protein, exhibit a specific f luorescence when cross-linked to proteins, and are mutagenic. Glycotoxins are transferred to the serum proteins of human smokers. AGE-apolipoprotein B and serum AGE levels in cigarette smokers were significantly higher than those in nonsmokers. These results suggest that increased glycotoxin exposure may contribute to the increased incidence of atherosclerosis and high prevalence of cancer in smokers.

Diabetic retinopathy: Some cellular, molecular and therapeutic considerations

“…84 Smokers have been shown to have higher levels of glycated lens proteins and more AGE immunoreactivity in coronary arteries than non smokers,85 and these findings are consistent with the knowledge that smoking is a risk factor for proteinuria and loss of vision in diabetics,86 although most studies thus far have failed to show a definite connection between smoking and progression of diabetic retinopathy.87…”

Secondhand tobacco smoke impairs neurogenic and endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle: improvement with chronic oral administration of L-arginine

“…Serum AGEs or LDL-linked AGEs are significantly elevated in cigarette smokers. 31 These evidence provide new insight into the pathogenesis of impotence associated with tobacco usage.…”

Idiopathic nodular glomerulosclerosis in a chronic marijuana user; a case report and review of the literature

“…It increases the risk of albuminuria, progression to proteinuria, and renal functional impairment, particularly in men and the elderly. The pathophysiologic mechanisms include the formation of advanced glycation end-products (AGEs) by glycotoxins, induction of oxidative stress, angiogenesis, and altered intrarenal hemodynamics (7,8). Induction of oxidative stress by free radicals contained in cigarette smoke and directly by AGE increases ECM.…”