The effect of systemic lipopolysaccharides on the cardiovascular system in Sprague-Dawley rats

Abstract

Literature has shown that there is a link between cardiovascular disease and cognitive deterioration. Cardiovascular and neurodegenerative diseases both share risk factors that include age, elevated cholesterol levels and blood pressure. Both conditions primarily affect middle aged and elderly populations and are characterised by a disruption in homeostasis. Research has found that systemic inflammation induces cardiovascular and neurological disease. In addition, cardiovascular disease is initiated the following: endothelial damage and inflammation, disrupting cellular (erythrocyte, fibrin network, platelet), cardiac myofibril and vascular morphology. Systemic inflammation may result if the cardiovascular system is exposed to bacteria or bacterial metabolites. Polysaccharides are long monosaccharide chains linked to glycosidic bonds that occur in nature. These structures serve as energy reserves and structural components in all organisms. The lipopolysaccharide endotoxin is a polysaccharide that is excreted from gram-negative bacteria and reside in gastrointestinal tract of healthy human beings. However, upon sustained abnormal gastrointestinal tract entry research suggests that lipopolysaccharides may aid in or play a primary role in the aetiology of cardiovascular disease and the neurodegenerative process through a low-grade systemic inflammatory immune response. The elderly may be are readily exposed to lipopolysaccharides through tooth loss (due to the dilation of the oral vasculature when tooth loss occurs) and impaired tight junction resulting in cardiovascular system entry. Research suggests that tooth loss and cardiovascular disease development are closely related through the resultant systemic inflammation. In addition, men experience an increased prevalence in various cardiovascular diseases that increase the risk of pathogenesis of neurodegeneration in a unique manner. This study forms part of a larger study that investigated effects of lipopolysaccharides on the brain, cardiovascular system and liver in which the Alzheimer’s disease population are the population of interest. The aim of this study was to investigate the effect of early endotoxin exposure on the cardiovascular system while also investigating its effect on cognition of male Sprague Dawley rats over a ten-day period. In addition, Manuka honey was introduced as a possible treatment for the systemic inflammatory effects of lipopolysaccharides. Cognitive and behavioural tests evaluated anxiety-like behaviour, mobility and short- and long-term, familiar object-, and spatial memory using the Open field-, Novel object recognition-, and Y-Maze test behavioural tests. The histological and ultrastructural analyses were conducted on the aorta, heart and blood following lipopolysaccharide exposure using light-, scanning electron- and transmission electron microscopy. The aorta and myocardial tissue were studied through light- and transmission electron microscopy found that myocardium exposure to lipopolysaccharides resulted in cardiac myofibril damage and mitochondrial cristae destruction. While Manuka honey treatment prevented a significant amount of myofibril damage. Nevertheless, the treatment failed to prevent mitochondrial cristae destruction. Aortic exposure resulted in cellular abnormalities, elastin fragmentation and collagen deposition. Manuka honey administration resulted in the reduction of cellular abnormalities and elastin fragmentation in the aorta however, the treatment induced collagen depletion. In addition, whole blood analysis through scanning electron microscopy, showed that the endotoxin resulted in a lack of erythrocyte and platelet morphological changes. However, exposure resulted in the abnormal formation of fused and thick aggregated fibrin networks. The therapeutic remedy assisted in counteracting the harmful effects of the endotoxin by producing fibrin fibres that were both standard in structure in some areas and thick and fused in structure in other areas. Early endotoxin exposure did not result in a significant behavioural or cognitive alteration. However, Manuka honey coupled with LPS was shown to impair spatial memory. In conclusion, cardiovascular organs such as the aorta, cardiac muscle and fibrin network morphology are vulnerable to the effects of short-term lipopolysaccharide exposure. Therefore, exposure may result in an elevation of cardiac-, aortic cellular and elastin destruction that may possibly conclude in cardiovascular disease and an elevation in thrombotic events. In addition, Manuka honey serves as an insufficient remedy for the harmful effects of lipopolysaccharides on the cardiovascular system.