A Regenerative Antioxidant Protocol of Vitamin E and α-Lipoic Acid Ameliorates Cardiovascular and Metabolic Changes in Fructose-Fed Rats

Abstract

Type 2 diabetes is a major cause of cardiovascular disease. We have determined whether the metabolic and cardiovascular changes induced by a diet high in fructose in young adult male Wistar rats could be prevented or reversed by chronic intervention with natural antioxidants. We administered a regenerative antioxidant protocol using two natural compounds: α-lipoic acid together with vitamin E (α-tocopherol alone or a tocotrienol-rich fraction), given as either a prevention or reversal protocol in the food. These rats developed glucose intolerance, hypertension, and increased collagen deposition in the heart together with an increased ventricular stiffness. Treatment with a fixed combination of vitamin E (either α-tocopherol or tocotrienol-rich fraction, 0.84 g/kg food) and α-lipoic acid (1.6 g/kg food) normalized glucose tolerance, blood pressure, cardiac collagen deposition, and ventricular stiffness in both prevention and reversal protocols in these fructose-fed rats. These results suggest that adequate antioxidant therapy can both prevent and reverse the metabolic and cardiovascular damage in type 2 diabetes.

Figure 1

(a): Plasma glucose concentrations following oral gavage of glucose (2 g/kg) recorded after 16 weeks for rats fed with corn starch (⬤), fructose (⚪), or fructose with α-tocopherol and α-lipoic acid as either prevention (FTPP) (▲) or reversal (FTPR) (▾) protocols. *P < .05 versus corn starch-fed rats. (b) Plasma glucose concentrations following oral gavage of glucose (2 g/kg) recorded after 16 weeks for rats fed with corn starch (⬤), fructose (⚪), or fructose with tocotrienol-rich fraction and α-lipoic acid as either prevention (FTTP) (▵) or reversal (FTTR) (▿) protocols. *P < .05 versus corn starch-fed rats; ^# P < .05 versus fructose-fed rats.

Figure 2

(a): Tail-cuff measurement of systolic blood pressure recorded at 0, 8, and 16 weeks for rats fed with corn starch (⬤), fructose (⚪), or fructose with α-tocopherol and α-lipoic acid as either prevention (FTPP) (▲) or reversal (FTPR) (▾) protocols. *P < .05 versus corn starch-fed rats. (b) Tail-cuff measurement of systolic blood pressure recorded at 0, 8, and 16 weeks for rats fed with corn starch (⬤), fructose (⚪), or fructose with tocotrienol-rich fraction and α-lipoic acid as either prevention (FTTP) (▵) or reversal (FTTR) (▿) protocols. *P < .05 versus corn starch-fed rats; ^# P < .05 versus fructose-fed rats.

Figure 3

Representative pictures of left ventricular interstitial collagen deposition in rats fed for 16 weeks with corn starch (a), fructose (b), fructose with α-tocopherol and α-lipoic acid as either prevention (FTPP) (c) or reversal (FTPR) (d) protocols, or fructose with tocotrienol-rich fraction and α-lipoic acid as either prevention (FTTP) (e) or reversal (FTTR) (f) protocols.