ABSTRACT

ABSTRACT:
Oxidative stress in an imbalance between the production of free radicals and antioxidants system in our body. When the concentration of free radicals is not controlled by our internal defensive mechanism (antioxidants or enzymes), the oxidative damage occurs to protein, lipids and DNA that leads to the genotoxicity and cytotoxicity and the disturbance in the metabolic pathways that create some major diseases which may lead to the death of a person. In these diseases, some are chronic and some are acute. Acute disease may be treat or cured properly by taking some drugs or maintain a healthy lifestyle but those disease that are prolonged or may be hereditary transferred, cannot be cured properly but may be decreased their effects on the person’s life and the life span may become increases. Some of the metabolic diseases may affect the other organs of human body which becomes severe and cannot be cured, include hypertension, it mostly affect the kidneys and become chronic day by day, in this disease the person may lead to the death because of high blood pressure that affect the coronary arteries of the heart and the person may suffer from time to time heart attacks or it may lead to the sudden death. Oxidative stress also linked to various types of cancers due to the oxidative damage to the DNA, it may affect the protein synthesis due to which the other organs of the human body becomes highly at risk of damage and the cancer occurs in these organs. Many organizations, Pharmacists, Doctors and physicians play a vital role in developing the proper cure or treatment of these formidable metabolic diseases. People should also aware of those things that create this growing menace to prevent themselves from these dreadful diseases.

INTRODUCTION:
We all know that energy production by metabolism is linked by some reactions and enzymes involved in it and metabolism of some nutrients involved in aging process.3 Aging related diseases such as diabetes, atherosclerosis and others are affected by metabolic syndromes.5
The cluster of multiple abnormalities in an individual such as diabetes, hyperglycemia, hypoglycemia, atherosclerosis, Alzheimer disease, obesity etc. is collectively called as metabolic syndromes.6,4 These diseases were demonstrated in Framingham study in 1970’s and Scandinavian study in 1980’s. The main reasons of these diseases are related to oxidative stress. These syndromes were highlighted the causes of coronary heart diseases. During the past 20 years these metabolic health risk has been known by their several names.6 However, they are collectively called as metabolic syndromes.6 The most common heart risk factors include central obesity, diabetes, hyperglycemia, high cholesterol and high blood pressure.2
About 20-25 % of world’s adult populations havemetabolic syndromes that cause the death and mostly the heart attacks or stroke. In fact, those people who have any one from the above syndromes have a fivefold greater risk of developing the diabetes type II. About 230 million people are the patients of diabetes nowadays, which is one of the most common chronic disease that leading to the death of an individual.4

OXIDATIVE STRESS:
An imbalance between free radicals and antioxidants in your body is called oxidative stress.3 Free radicals are the molecules that contain oxygen with an uneven numbers of electrons, these electrons allows them to react with other molecules and causes the large chain chemical reactions in your body.3
ANTIOXIDANTS:
The molecules that donate an electron to a free radical without making themselves unstable, causes the free radicals to stabilize and less reactive are called antioxidants.1
EFFECTS OF OXIDATIVE STRESS ON THE BODY:
Oxidation is normal and metabolic process but whenever the concentration of oxygen is increased in our body and causes the oxidative stress, the free radicals start damaging the fatty tissues, DNA, and proteins in our body. So this damage can lead to the variety of diseases cause in our body.1

RISK FACTORS RELATED TO METABOLIC SYNDROMES:
In general, the presence of metabolic syndromes refers to 1.78 times relative risk of cardiovascular events and death compared with healthy individual.1 Notably, women mostly suffer from these diseases, about 1.33 times higher than men.1
Although everyone produces some free radicals in their body through processes like inflammation or exercise. This is the normal part of our body’s system and healthy lifestyle.
We may be exposed to these free radicals in our environment, these includes…
• Ozone
• Certain pesticides ; cleaners
• Cigarette smoke
• Radiation
• Pollution
• A diet with high sugar, fat and alcohol may also contribute to free radicals.1

METABOLIC DISORDERS:
Here, we are discussing some metabolic disorders that are related to cardiovascular diseases or may lead to death.
1. DIABETES:
Type II diabetes is the main cause of premature illness or death, mainly due to the increased risk of CVD. In which the blood glucose levels are high enough for a person. The diabetes may also leads to the blindness, amputation and kidney failure. 7
The majority of clinical trials reported the effects of botanicals on inflammatory biomarkers in diabetic patients. These patients deserve special attention for intensive management of hyperglycemia ; other metabolic disorders.6 In this disease the primary goal of antihyperglycemic therapy is to decrease hemoglobin A1C to less than 7 %. These patients are given some drugs to prevent from the major metabolic disorders such as obesity, insulin resistance.7 Diabetes is the hereditary disorder in which the glucose level is raised in the patient’s body due to the less enzymatic action or deficiency of some enzymes that helps in the metabolism of glucose.7 In this disease, the person’s weight is loss at very short intervals. Glucose is not absorbed by cells and remain in blood that causes the release of more and more insulin and the production of extra amount of insulin weakens the body and may eventually wear out the beta cells.6 Once the pancreas is no longer able to produce enough insulin than a person becomes hyperglycemic and will be diagnosed with type II diabetes.2
2. HYPERTENSION:
An elevation of systolic and diastolic pressure is another metabolic disorder.1 These patients have normal blood pressure levels about 140/90 mm Hg are considered as elevated. Those patients are highly at risk of CVD.7 In this category, patients are mostly suffer from diabetes mellitus, chronic kidney diseases, coronary artery diseases.7
3. CENTRAL OBESITY:
Obesity is related to the insulin resistance. It contributes to hypertension, hyperglycemia, high serum cholesterol and low HDL-C and these lead to the CVD.4 In this disorder the person’s BMI is increased due to the increase in body mass, and the fatty deposits on the abdomen. Adipose tissues are considered to be the site of energy that could be generate if needed, that’s why they are the active source of inflammatory cytokines and substances that can promote the atherosclerosis. This tissue can cause the abnormalities in liver and muscles owning to alternations or levels of fatty acids within the cells and related changes in fatty acid oxidation.2
4. ATHEROGENIC DYSLIPIDEMIA:
It is the another metabolic syndrome caused by the increased in triglycerides level, low HDL-C, and high LDL-C. These patients have elevated concentration of apoB, a lipoprotein whose concentration indicates the presence of highest atherogenic potential. However, apoB concentration may give the clear representation of CVD than LDL-C.3
5. PROTHROMBOTIC AND PRO-INFLAMMATORY STATE:
Fibrinogen and other activators and inhibitors, and C- reactive proteins and elevated with high levels in some patients with some metabolic disorders, resulting in prothrombotic and pro-inflammatory effect. C-reactive protein is highly sensitive protein i-e greater than about 3mg/dl represent the state of inflammation and highly risk of ASCVD.4
6. INSULINE RESISTANCE:
It is the state in which normal tissues do not able to target their respective tissues. In this disease, insulin is not able to promote glucose uptake, inhibit hepatic glucose production and suppress lipolysis.7Hyperinsulinemia is developing in this state, and pancreas is unable to secrete sufficient amount of insulin to maintain glucose hemostasis. This disease is associated with increased risk of ASCVD, and it also relates with the type II diabetes.6
7. CLASSIC GALACTOSEMIA:
The inborn error of galactose metabolism, which is caused by the deficiency of enzyme galactose 1-phosphate uridyltransferase, resulting in accumulation of metabolites galactitol and galactose 1-phosphate. Patients take galactose which cannot be digested by enzymes and remain in blood. Mason and Turner now invented the galactose free milk for infants to prevent them from this condition. The most troubling situation is that when the person continuously takes the galactose free diet is becomes suffer from the long term diseases and the metabolic syndromes.8

8. BREAST CANCER:
It has been declared that the association of individual components of the metabolic syndromes is with breast cancer. The mechanism by which the breast cancer is associated with metabolic syndromes is still unknown. Insulin may exert its effect directly on epithelial cells by activating AKT and ERK pathways which have important roles in tumorigenisis, it also stimulate the breast cancer cells synergistically with oestradiol. 9
9. ALZHEIMER’S DISEASE:
In this disease, inflammation occurs in peripheral tissues that lead to multiple impairing or cell functions and body metabolism. In AD, tumors necrosis levels and reactive oxygen species increases in the brain tissues. Neurotoxicity and neurodegeneration occurs in metabolic stress. Metabolic stress also includes disturbances in proteostasis and activation of signaling pathways that mediate cellular stress.11
10. HYPERGLYCEMIA:
It is a chronic stress which is due to either reduced uptake of glucose by cells or increased synthesis of glucose. To maintain glucose hemostasis, the adrenocorticotropic activity is elevated during stress; due to this all glucose pathways would be affected.7 In the glycolytic pathway under stressful condition, the pyruvate produce higher amount of lactate anaerobically because of the reduced activity of pyruvate dehydrogenase, in spite of this the TCA cycle activity will be high because of the availability of substrates for TCA cycle by the oxidation of lipids.11
RECENT RESEARCH:
In women and men, metabolic syndromes were seen in 10% and 15% of subjects with NGT, 42% and 64% of those with type II diabetes. The risk of coronary heart diseases and stroke was increased threefold in subjects with the syndromes (P