الفهرس 
Review of literatureOnly 14 pages are availabe for public view
 |  | from | 233 |  |  |
| | | from | 233 | | |
Abstract
Sepsis represents a serious medical condition characterized by systemic inflammatory condition that can be defined as a progressive failure of the circulation, clinically characterized by systemic hypotension, hyporeactiveness to vasoconstrictors and subsequent function abnormities followed by multiple organ failure. Septicaemia causes by Gram-negative pathogens; it is a dangerous infection which is associated with a major cause of morbidity and mortality. Sepsis is associated with multiple organ dysfunctions, including cardiovascular complications because of the vicious cycle of inflammation and coagulation and often leads to death.
Lipopolysaccharides (LPS), a cell wall component of Gram- negative bacteria, causes severe inflammation, systemic inflammatory response syndrome and septic shock. Oxidative damage induced by LPS injection results in the overproduction of free radicals, including reactive-oxygen species (ROS). LPS has been suggested to be very useful for the study of oxidative damage in laboratory animals, which was thought to induce the cardiovascular dysfunction.
L-carnitine is an essential factor for the transfer of long- chain fatty acids from the cytosol to mitochondria for subsequent β- oxidation. The supplementation of carnitine to septic patients lead to increase in the rate of oxidation of fatty acids and normalize lipids metabolism. Also, L-carnitine has been shown to have enhancement effects in patients with severe cardiovascular disorders, such as coronary heart disease, chronic heart failure and peripheral vascular disease.
Coenzyme-Q10 is a compound which serves as coenzyme in key enzymatic reactions during the energy production in the cell. It is a naturally occurring fat-soluble vitamin-like. Quinone is
commonly known as CoQ10. Also, it has the ability to transfer electrons where it acts as an antioxidant. Low levels of CoQ10 were found in both serum and tissues of patients with chronic cardiac failure. It is noted that CoQ10 provides improvement in treatment of stroke and myocardial infarction. Therefore, the beneficial dietary effects of CoQ10 on clinical applications have been reported to ameliorate cardiovascular disease such as congestive heart failure, cardiomyopathy and mitochondrial disorder in humans.
Alpha-lipoic acid (ALA), a disulphide derivative of octanoic acid, and its reduced form dihydrolipoic acid (DHLA) are natural compounds widely distributed in plants and animals. They are synthesized through a reaction catalyzed by lipoic acid synthase within the mitochondria. The therapeutic actions of ALA are based on unique antioxidant ALA/DHLA system. Thus, DHLA is able to reduce not only reactive oxygen species (ROS) but also oxidize forms of other antioxidants. ALA regenerates other antioxidants and for this reason it is called an antioxidant of antioxidants. Several authors investigated the protective effect of ALA against myocardial ischemia-reperfusion injury (IRI). They suggested that the cardioprotective effects of ALA on IRI are through a mechanism involving myocardial aldehyde dehydrogenase-2 (ALDH-2) activation.
The current work was designed to scrutinize the curative effects and antioxidant potentials of L-carnitine alone or associated with CoQ10 or/and ALA on myocardial dysfunction in septic rats induced experimental with lipopolysaccharides (LPS). The underlying mechanisms through those antioxidants that counteracted myocardial dysfunction in septic rats were discussed according to available published researches.
Therefore, this study was undertaken to investigate the disturbance in the physiological and biochemical parameters in septic rats. In addition, this work aimed to focus on the beneficial
role of treatment by L-carnitine alone or with coenzyme Q10 or α- lipoic acid as well as their mixture in retardation and regression of septicaemia associated with cardiovascular dysfunction in rats.
To achieve this propose, sixty adult male albino rats were employed in this work.This study was included two experiments and carried out as the following: In the first experiment, the rats were randomly divided into two main groups. In the first rats group,
15 rats were injected intraperitoneally (i.p) with saline solution and served as normal control rats group. The second animals group (45 septic rats), these rats were injected intraperitoneally (i.p) with a single dose of LPS (5mg/kg body weight). After three days of LPS injection (induction of endotoxin), five rats from each previous group were taken to compare the alterations in the serum heart enzymes profile, biochemical markers, lipids profile and cytokines profile as well as the changes in oxidative and antioxidant status in the heart tissues due to experimentally induction of sepsis associated with cardiovascular disease (CVD) in rats. In the second experiment (50 rats), five comparisons were made between normal control animals group (10 rats) and four septic (LPS) subgroups of animals (40 rats); 10 rats in each one. The first septic rats subgroup was treated daily with 200mg L-carnitine/kg body weight by oro- gastric tube for 14 days (LPS+LC subgroup). The second septic rats subgroup was treated daily with both 200mg L-carnitine and 200mg coenzyme Q10/kg body weight by oro-gastric tube for the same previous period (LPS+LC+CoQ10 subgroup). The third septic rats subgroup was treated daily with both 200mg L-carnitine and 100mg α-lipoic acid/kg body weight by oro-gastric tube for the same manner (LPS+LC+ALA subgroup). Finally, the fourth septic rats subgroup was treated daily with a combination of L-carnitine, coenzyme Q10 and α-lipoic acid by oro-gastric tube for the same pattern period (LPS+LC+CoQ10+ALA subgroup). All animals in the previous subsets and normal control group were divided into two periods (7&14 days).
The obtained data revealed remarkable disturbances in serum heart enzymes profile (CK,CK-MB, LDH and AST), cardiac profile (H-FABP, myoglobin, endothelin-1, resistin and total nitric oxide), lipids profile (total cholesterol, triglycerides, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol) and cytokines profile (tumour necrosis factor-α, interleukin-1β and interleukin-6) in septic rats than those in normal control ones. Also, considerable alterations were obtained in the oxidative and antioxidant status (hydrogen peroxide, malondialdehyde, reduced glutathione, oxidized glutathione, GSH/GSSG ratio, glutathione peroxidase, superoxide dismutase and catalase) in homogenate heart tissues of septic rats than those in normal control ones.
When septic rats group was treated with L-carnitine alone or with coenzyme Q10 or α-lipoic acid as well as their mixture for 7 or 14 days a considerable amelioration effects in all previous studied parameters were pronounced dependent on time of treatment.
In conclusion, treatment with L-carnitine alone or associated with CoQ10 or/and ALA can reduce cardiac dysfunction as a result of induction septicaemia in rats due to the synergistic effects of their pharmcoadynamic and pharmacokinetic properties . Also, this investigation can practically help to encourage the clinical use of a mixture of these compounds as an aid treatment of cardiac dysfunction in septic rats (endotoxaemia).
So, future researches are needed to evaluate the potential adverse effects of L-carnitine, CoQ10 and ALA on the treatment of cardiac dysfunction in septic rats. Studies conducted utilizing human subject need to include medical cardiac and vascular examinations in order to get a more accurate representation of the treatment effects on heart and vascular functions.