Cod liver oil supplementation improves cardiovascular and metabolic abnormalities in streptozotocin diabetic rats

Abstract

Abnormalities in the metabolism of essential fatty acids and the results of increased oxidative stress have been implicated in cardiovascular disorders observed in diabetes mellitus. This study, therefore, aimed to investigate the effects of cod liver oil (CLO, Lysi Ltd, Iceland), which comprises mainly an antioxidant vitamin A, n:3 polyunsaturated fatty acids (n:3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cardiovascular abnormalities in streptozotocin (STZ)-diabetic rats. Two days after single STZ (55 mg kg(-1), i.p.) or vehicle injection, diabetes was verified by increased blood glucose, and non-diabetic and diabetic rats were left untreated or treated with CLO (0.5 mL kg(-1) daily, by intragastric probing) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic rats; CLO provided better weight gain, entirely prevented the plasma lipid abnormalities, but partially controlled the glycaemia in diabetic rats. In isolated aorta rings, diabetes resulted in increased phenylephrine-induced vasoconstriction and isoprenaline-induced vasorelaxation, impaired endothelium-dependent vasodilatation and unchanged responsiveness to sodium nitroprusside. CLO treatment completely prevented endothelial deficiency, partly corrected the phenylephrine-induced vasoconstriction and did not affect the responses to isoprenaline and sodium nitroprusside in diabetic aorta. Diabetes also produced a marked decrease in the rate of spontaneously beating right atria and a significant increase in basal contractile force of left ventricular papillary muscle. The responsiveness of right atria to the positive chronotropic effect of isoprenaline was significantly decreased in diabetic rats, and was increased in CLO-treated diabetic rats. The positive chronotropic effect of noradrenaline was markedly increased in diabetic atria, but prevented by CLO treatment. Diabetes also resulted in an increased positive inotropic response of papillary muscle to both noradrenaline and isoprenaline, which were prevented by CLO treatment. CLO treatment also resulted in lower tissue sensitivity (pD(2)) to these agonists in diabetic papillary muscle. Ventricular hydroxyproline content was found to be unchanged among the experimental groups. The ultrastructure of diabetic myocardium displayed various degenerations (i.e. intracellular oedema, myofibrillar fragmentation, condensed pleomorphic mitochondria, thick capillary irregular basement membrane, swollen endothelial cells), which were partially prevented by CLO treatment. We conclude that the supplementation with CLO is effective in preventing cardiovascular disorders observed in experimental diabetes.

Glycoxidative Stress and Cardiovascular Complications in Experimentally-Induced Diabetes: Effects of Antioxidant Treatment

“…intracellular oedema, myofibrillar fragmentation, condensed pleomorphic mitochondria, thick capillary irregular basement membrane and swollen endothelial cells) was associated with mechanical alterations caused by adrenergic agonists [21]. Long-term experimental IDDM, characterized by ventricular remodeling, overt resting left ventricular sys systolic dysfunction and decreased left ventricular responsiveness to beta-adrenergic receptor stimulation is associated with histopathological changes indicating dilatational remodeling as increased capillary tortuosity and type IV collagen in capillaries and cardiomyocytes [22]. Insulin replacement therapy in STZ-diabetic rats can prevent these changes [19, 20], and thyroid hormones mediate the effect of insulin therapy [19].…”

“…More recently, endothelin A receptor antagonists, atresantan or 1-methylnicotinamide, a primary metabolite of nicotinamide preserved endothelium-dependent relaxation in diabetic vessels [144, 145]. Interestingly, a considerable body of evidence suggests that increasing NO bioavailability via antioxidant therapy is an important intervention not only for endothelial dysfunction but also other cardiovascular abnormalities induced by DM [22, 63, 68, 119]. …”

“…Experiments from “the ADIC Study Group”, observed the effectiveness of exogenous antioxidant treatments in the recovery of OS markers and endogenous antioxidant enzyme activities in STZ-diabetic rats [22, 63, 64, 154, 159-161]. These recoveries were associated with the amelioration in vascular and cardiac metabolism/function [22, 46, 63, 64, 69, 95, 119, 142, 147, 148, 154, 159-161].…”

Dietary flaxseed supplementation improves endothelial function in the mesenteric arterial bed

“…It has been shown that dietary fish oil rich in EPA and DHA can reduce blood pressure and enhance vasorelaxant responses, providing an important cardiovascular protective effect of omega-3 PUFAs (Ceylan-Isik et al, 2007;Cicero, Ertek, & Borghi, 2009;Lawson, Mehta, Saldeen, Mehta, & Saldeen, 1991;Mindrescu et al, 2008).…”

Vitamin D and Diabetes

“…In obese Wistar rats, a significant decline in glucose levels in all animals supplemented with vitamin D 3 was found [32]. In addition, feeding of vitamin-Dcontaining cod liver oil to streptozotocin-induced diabetic rats partially improved their blood glucose levels as well as their cardiovascular and metabolic abnormalities [33]. From these preclinical data it is reasonable to consider that vitamin D and its metabolites have the potential to positively influence the glycemic status and as such prevent or ameliorate diabetes, at least in cases of (mild) vitamin D deficiency.…”