Efficacy of Caffeic Acid on Diabetes and Its Complications in the Mouse.

Nada Oršolić,Lidija Šver,Vedran Balta,Dyana Odeh,Damir Sirovina,Maja Jazvinšćak Jembrek,Goran Gajski

doi:10.3390/molecules26113262

Abstract

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg−1). Two days later, CA (50 mg kg−1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.

Highlights

Diabetes mellitus (DM) is characterized by high blood sugar, dysregulated carbohydrate and lipid metabolism and oxidative stress, coupled with a high incidence of microvascular disorders [1,2]
On the 10th day of all treatments, the body weight of diabetic mice demonstrated significant weight loss when compared with the control mice; the decrease was the largest between the 3rd and 10th day (−3.75 to −12.10%), and at the end of the 45th day, there was a significant difference in the weight of the control and the diabetic untreated mice
Statistical analyses showed that alloxan treatment, when in whole blood cells are measured, increased DNA damage compared to the control animals (P < 0.05); the results show that alloxan increased the percentage of DNA in tails by 47.23% (3.46 ± 0.16 versus 2.35 ± 0.13) in relation to control animals

Summary

Introduction

Diabetes mellitus (DM) is characterized by high blood sugar (hyperglycemia), dysregulated carbohydrate and lipid metabolism and oxidative stress, coupled with a high incidence of microvascular disorders [1,2]. T1D accounts for 7–12% of the total diabetes population and leads to long-term complications including cardiovascular disease According to epidemiological data, impaired glycemic control, lipoprotein disturbances, oxidative stress and inflammation are important parameters that can accelerate atherosclerosis. Except for LDL-c, elevated serum triacylglycerol (TG), total cholesterol (TC) and very-low-density lipoprotein-cholesterol (VLDL-c) concentrations out of their reference intervals are often indications of dyslipidemia and an increased incidence of CVD. Atherogenesis is a process in vascular tissues, facilitated by cellular and acellular elements and resulting in the formation of atheromatous plaques on the inner walls of arteries, which causes the narrowing of blood flow channels as well as the hardening of artery walls (atherosclerosis) with lesions of the coronary and blood vessels responsible for the pathogenesis of various cardiovascular and cerebrovascular diseases

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