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CHAPTER ONE 1.1 INTRODUCTION 1.1.1 Pro-oxidant Effect Pro-oxidants are chemicals that induce oxidative stress, either by generating reactive oxygen species or by inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues, for example an overdose of the analgesic paracetamol (acetaminophen) can fatally damage the liver, partly through its production of reactive oxygen species. Some substances can serve as either antioxidants or pro-oxidants, depending on conditions. Some of the conditions that are important include the concentration of the chemical and if oxygen or transition metals are present. While thermodynamically very favored, reduction of molecular oxygen or peroxide to superoxide or hydroxyl radical respectively is fortunately spin forbidden. This greatly reduces the rates of these reactions, thus allowing aerobic life to exist. As a result, the reduction of oxygen typically involves either the initial formation of singlet oxygen, or spin-orbit coupling through a reduction of a transition-series metal such as manganese, iron, or copper. This reduced metal then transfers the single electron to molecular oxygen or peroxide. 1.1.2 Antioxidant Lipid Peroxidation Antioxidants are molecules that inhibit the oxidation of other molecules. Oxidation is a chemical reaction that can produce free radicals, leading to chain reactions that may damage cells. Antioxidants such as thiols or ascorbic acid (vitamin C) terminate these chain reactions. The term "antioxidant" is mainly used for two different groups of substances: industrial chemicals which are added to products to prevent oxidation, and natural chemicals found in foods and body tissue which are said to have beneficial health effects. To balance the oxidative state, plants and animals maintain complex systems of overlapping antioxidants, such as glutathione and enzymes (e.g., catalase and superoxide dismutase) produced internally or the dietary antioxidants: vitamin A, vitamin C, and vitamin E. Antioxidant dietary supplements have not been shown to improve health in humans, or to be effective in preventing diseases. This includes supplements of beta-carotene, vitamin A, and vitamin E having no effect on mortality rate or cancer risk. Supplementation with selenium or vitamin E does not reduce the risk of cardiovascular disease. 1.1.3 Lipid Lipids Are Classically Divided into Two Groups: Apolar and Polar. Triglycerides (apolar), stored in various cells, but especially in adipose (fat) tissue, are usually the main form of energy storage in mammals. Polar lipids are structural components of cell membranes, where they participate in the formation of the permeability barrier of cells and subcellular organelles in the form of a lipid bilayer. The major lipid type defining this bilayer in almost all membranes is glycerol-based phospholipid. The importance of the membrane lipid physical (phase) state is evidenced by the fact that lipids may control the physiological state of a membrane organelle by modifying its biophysical aspects, such as the polarity and permeability. Lipids also have a key role in biology as signaling molecules. 1.1.4 Lipid Peroxidation Lipid peroxidation can be described generally as a process under which oxidants such as free radicals or nonradical species attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs) that involve hydrogen abstraction from a carbon, with oxygen insertion resulting in lipid peroxyl radicals and hydroperoxides. Glycolipids, phospholipids (PLs), and cholesterol (Ch) are also well-known targets of damaging and potentially lethal peroxidative modification. Lipids also can be oxidized by enzymes like lipoxygenases, cyclooxygenases, and cytochrome. In response to membrane lipid peroxidation, and according to specific cellular metabolic circumstances and repair capacities, the cells may promote cell survival or induce cell death. Under physiological or low lipid peroxidation rates (subtoxic conditions), the cells stimulate their maintenance and survival through constitutive antioxidants defense systems or signaling pathways activation that upregulate antioxidants proteins resulting in an adaptive stress response. By contrast, under medium or high lipid peroxidation rates (toxic conditions) the extent of oxidative damage overwhelms repair capacity, and the cells induce apoptosis or necrosis programmed cell death; both processes eventually lead to molecular cell damage which may facilitate development of various pathological states and accelerated aging. The impact of lipids oxidation in cell membrane and how these oxidative damages are involved in both physiological processes and major pathological conditions have been analysed in several reviews. The overall process of lipid peroxidation consists of three steps: initiation, propagation, and termination . In the lipid peroxidation initiation step, pro-oxidants like hydroxyl radical abstract the allylic hydrogen forming the carbon-centered lipid radical (L•). In the propagation phase, lipid radical (L•) rapidly reacts with oxygen to form a lipid peroxy radical (L•) which abstracts a hydrogen from another lipid molecule generating a new (that continues the chain reaction) and lipid hydroperoxide (LOOH). In the termination reaction, antioxidants like vitamin E donate a hydrogen atom to the species and form a corresponding vitamin E radical that reacts with another forming nonradical products. Once lipid peroxidation is initiated, a propagation of chain reactions will take place until termination products are produced. 1.1.5 Medicinal Plants in brief The term “medicinal plant” include various types of plants used in herbalism ("herbology" or "herbal medicine"). It is the use of plants for medicinal purposes, and the study of such uses. The word “herb” has been derived from the Latin word, “herba” and an old French word “herbe”. Now a days, herb refers to any part of the plant like fruit, seed, stem, bark, flower, leaf, stigma or a root, as well as a non-woody plant. Earlier, the term “herb” was only applied to non-woody plants, including those that come from trees and shrubs. These medicinal plants are also used as food, flavonoid, medicine or perfume and also in certain spiritual activities. Traditional systems of medicine continue to be widely practised on many accounts. Population rise, inadequate supply of drugs, prohibitive cost of treatments, side effects of several synthetic drugs and development of resistance to currently used drugs for infectious diseases have led to increased emphasis on the use of plant materials as a source of medicines for a wide variety of human ailments. 1.1 JUSTIFICATION Reason for the finding The reason for this finding is to determine the inhibiting the effect of Siam leave (Chromolena Odorata) against Sodium Nitroprusside induce lipid peroxidation in selected rat tissues specifically the liver, kidney and brain. Oxidative Stress Oxidative stress is an imbalance between free radicals and antioxidants in a patient body. Free radicals are oxygen-containing molecules with an uneven number of electrons. The uneven number allows them to easily react with other molecules. Free radicals can cause large chain chemical reactions in a patient body because they react so easily with other molecules. These reactions are called oxidation. They can be beneficial or harmful. Like an apple turns brown when exposed to air, cells can “rust” when we breathe due to oxidative stress, a process caused by free radicals. Oxidation is a normal and necessary process that takes place in a patient body. Oxidative stress, on the other hand, occurs when there’s an imbalance between free radical activity and antioxidant activity. When functioning properly, free radicals can help fight off pathogens. Pathogens lead to infections. Major concentrate factors for Different Chronic Diseases 1. Chronic obstructive pulmonary disease (COPD) 11 % of older adults were treated for COPD, a disease that includes two main conditions—emphysema and chronic bronchitis. COPD makes it hard to breathe and causes shortness of breath, coughing, and chest tightness. • The number one way to prevent COPD—or slow it’s progression—is to quit or avoid smoking. Also to avoid second hand smoke, chemical fumes, and dust, which can irritate the lungs. • If already have COPD, complete the treatments that a patient doctor has prescribed, get the flu and pneumonia vaccines as recommended by a patient doctor, and continue to remain active. 2. Alzheimer’s disease and dementia 11% of older adults on Medicare were treated for Alzheimer’s Disease or another form of dementia. Alzheimer’s Disease is one specific type of dementia—a condition that causes memory loss and difficulty thinking or problem-solving to the point that it interferes with every day activities. Dementia is not a normal part of aging and is caused by changes in the brain over time. The biggest risk factors for these conditions are things a patient often can’t control, including age, family history, and genetics, but studies have suggested incorporating the following habits into a patient life style could slow or prevent onset. • Exercise. Staying active isn’t just good for a patient heart; it’s also great for a patient brain. • Sleep. A patient brain does important stuff while a patient are sleeping, so getting at least 7 hours of deep sleep a night is crucial • Be smart about a patient diet. Research suggests that some foods can negatively affect a patient brain 3. Depression 14% of older adults sought treatment for depression – a treatable medical condition that is not a normal part of aging. Depression causes persistent feelings of sadness, pessimism, hopelessness, fatigue, difficulty making decisions, changes in appetite, a loss of interest in activities, and more. Steps a patient can take to help with depression include: • Manage stress levels. Reach out to family and friends during rough spells and consider regular meditation • Eat a healthy diet. What a patient put into a patient body can affect a patient mood, so focus on foods that are high in nutrients and promote the release of endorphins and those “feel good” chemicals, and limit consumption of things like alcohol, caffeine, artificial sweeteners, and highly processed foods. • Routine exercise. Exercise has a number of physical and psychological benefits, including improving a patient mood through the release of endorphins and other “feel good” brain chemicals, boosting self-confidence and self-worth through meeting goals and improving a patient physical appearance, and increased socialization through interactions at gyms and group classes. • Talk to a patient doctor. If a patient’ve experienced any of the warning signs of depression, talk to a patient doctor, and ask about a patient treatment options. Antidepressant medications or psychotherapy could be right for a patient. If a patient or someone a patient love has had thoughts of suicide, call the National Suicide Prevention Lifeline at 1.800.273.8255 (TALK). 4. Heart Failure 14% of older adults were treated for heart failure — a condition that occurs when the heart cannot adequately supply blood and oxygen to all of the organs in the body. The heart might become enlarged, develop more muscle mass, or pump faster in order to meet the body’s needs, causing a patient to feel tired, light headed, nauseous, confused, or lack an appetite. The best prevention is to follow a doctor’s recommendations to decrease a patient risk for coronary heart disease and high blood pressure. 5. Chronic kidney disease (CKD) 18% of older adults were treated for CKD or a slow loss in kidney function over time. People dealing with CKD have an increased risk for developing heart disease or kidney failure. A patient can do the following to prevent or diminish symptoms of CKD: • Understand what damages a patient kidney. Diabetes and high blood pressure are the greatest risk factors for kidney damage, so taking steps to prevent these diseases is a patient best strategy • Early detection and treatment. Talk to a patient doctor regularly, stay current on screenings,and keep up on prescriptions a patient need to diminish symptoms 6. Diabetes 27% of older adults were treated for diabetes – a disease that occurs when a patient body is resistant to, or doesn’t produce enough, insulin. Insulin is what a patient body uses to get energy from food, and distribute it to a patient cells. When this doesn’t happen, a patient get high blood sugar, which can lead to complications such as kidney disease, heart disease, or blindness. Chances of having diabetes increases after age 45. To keep a patient from developing diabetes or to manage this condition, a patient doctor may suggest: • Eating a healthy diet, including monitoring a patient carbohydrate and calorie intake, and talking to a patient doctor about alcohol consumption • Exercising for 30 minutes five times a week to keep a patient blood glucose levels in check, and to control weight gain • Safely losing 5-7% of body weight if a patient are diagnosed with pre-diabetes 7. Ischemic heart disease (or coronary heart disease) 29% of older adults were treated for ischemic heart disease – a condition that is caused by a build-up of plaque that narrows the arteries leading to the heart. Narrow or blocked arteries decreases the amount of oxygen-rich blood delivered to the heart. This can cause other complications like blood clots, angina, or a heart attack. Habits a patient can incorporate to help: • Refrain from saturated and trans fats, and limit sugar and salt intake • Get 7-8 hours of sleep each night • Keep a patient stress levels in check • Do regular cardio exercises • Abstain from smoking • Talk to a patient doctor about the major risk factors, including high cholesterol and high blood pressure 8. Arthritis 31% of older adults were treated for arthritis – an inflammation of a patient joints, which causes pain and stiffness and is more common in women. There are steps a patient can take to delay the onset of arthritis or manage the symptoms, including: • Exercise at least 5 times per week, for 30 minutes each time to improve function and decrease pain. Try to include a mixture of aerobic, strength-building and stretching movements. • Stay within the recommended weight for a patient height—losing one pound can remove four pounds of pressure on a patient knees • Make sure a patient back, legs and arms are always supported • Take precautions to avoid joint injuries • Do not smoke 9. High cholesterol 47% of older adults were treated for high cholesterol – a condition that occurs when a patient body has an excess of bad fats (or lipids), resulting in a patient arteries getting clogged, which can lead to heart disease. Lifestyle factors a patient can control when it comes to preventing or managing high cholesterol include: • Abstaining from smoking and excessive alcohol consumption • Being active each day • Managing a patient weight • Minimizing saturated fats and trans fats in a patient diet 10. Hypertension (high blood pressure)