This section will focus on the details of what is known about how doxorubicin treatment and type 2 diabetes mellitus (T2DM) cause cellular iron dysregulation and increased oxidative stress. Thorough background on iron metabolism, doxorubicin and T2DM and how these relate to iron regulation will be described. Regulation of iron storage will be proposed as an additional mechanism whereby metformin can ameliorate the oxidative stress induced by doxorubicin and T2DM.
Iron Metabolism
Iron plays an essential role in virtually all organisms from bacteria to humans. In addition to binding oxygen in heme, it participates in many other cellular events including DNA synthesis and electron transfer in the electron transport chain. Despite it being the most abundant element on earth (97), iron has very low bioavailability. Iron is therefore highly conserved in organisms; humans do not have an excretion pathway for iron, but instead regulate iron at the level of absorption. Once absorbed, iron continues to be regulated because it is also highly reactive with oxygen. Figure 1 shows the Haber-Weiss and Fenton reactions, which readily occur under physiological conditions with free iron and oxygen or hydrogen peroxide to produce free radicals. These free radicals will cause damage in the cell and contribute to oxidative stress (67, 97). Iron absorption, transport, and storage are therefore highly regulated and the disruption of iron metabolism has been implicated in several diseases.
The mechanism of iron absorption and transport is well known and is briefly described here. Non-heme and heme iron are absorbed into the enterocyte through DMT1 and heme carrier protein 1, respectively (5, 67, 97). Once inside the enterocyte, the iron can be stored in...
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...tress, the iron-sulfur clusters dissociate, causing a conformational change, and aconitase becomes IRP-1(3). This has possible implications for the relationship between iron homeostasis, oxidative stress and metabolism which will be discussed in more detail later.
In summary, iron is an important and highly reactive element involved in several cellular processes. Iron absorption occurs through DMT1 and heme carrier protein 1, is transported to cells via transferrin, and is endocytosed upon binding TfR1. Once inside the cell, iron is either transferred to mitochondria, stored in ferritin, or released into the labile iron pool. Iron transport out of the cell occurs via ferroportin, of which hepcidin is a potent inhibitor. Iron homeostasis can be disrupted, which increases cellular oxidative stress and contributes to the etiology of different diseases (5, 30, 67, 97).
Read Case 12 The Folic Acid Fortification Decision: Before and After on pages 351-363 of your text. Once you have read the case, you are to address these questions. The word limit per response is 200 words.
...ces in any of the blood variables measured nor in body weight or organ weight over the three different time periods. This finding led Anderson et. al. to conclude that chromium picolinate is not toxic at levels on a per kilogram basis even at several times the upper limit of estimated safe intake for humans (Anderson 273-9). On the other hand, a more recent study conducted by Speetjens et. al. in 1999 showed the chromium picolinate cleaves DNA. Chromium picolinate, if it is incorporated directly into a cell, is reduced by ascorbate and thiols into a hydroxyl radical that quite readily cleaves DNA – indicating that further research on the dangerous side effects of chromium picolinate are necessary to ensure its safe usage (Speetjens 483-7). Once again, it is evident that Stimulife 750 is not as harmless as it purports to be based on its ingredients.
Homeostasis is essential to the cell’s survival. The cell membrane is responsible for homeostasis. The membrane has a selective permeability which means what moves in and out of the cell is regulated. Amino acids, sugars, oxygen, sodium, and potassium are examples of substances that enter the cell. Waste products and carbon dioxide are removed from the cell.
Metformin is prescribed for long-term treatment of Type II Diabetes Mellitus. It can be used alone or in combination with other drugs for diabetes management as part of a health plan that includes proper diet and exercise. Metformin, which has a low affinity for plasma protein binding, limits glucose production in the hepatic system, lowers absorption of glucose in the intestines and improves insulin sensitivity by enhancing uptake and utilization of glucose (FDA, 2008). This drug does not cause an increase in insulin, making it less likely to cause a patient to become hypoglycemic compared with other common antihyperglycemic medications.
Hemochromatosis is a disease which makes your body absorb all of the iron in food, instead of regulating iron intake. Hemochromatosis “attacks” the entire body, especially the places where most of the iron normally goes: the bloodstream and liver. Some symptoms of this disease are bone and joint discomfort, liver problems, irregular heartbeat, and an unusual bronzing of the skin. Armand Trousseau first described it in 1865 as Diabetes bronze, due to people with diabetes showing the bronze-skin symptom. It was thought to be quite rare at the time. About “⅓ or ¼ of people of Western European descent have th...
Kidney dialysis comes at a price. With chronic kidney disease (CKD), there can be problems with iron depletion. Dialysis slowly depletes a patient of iron. On average, about 5-7 mg of iron is lost in each session. Until recently, the main way doctors tried to compensate for this loss was by adding 100 mg of iron into the bloodstream. This treatment comes with risks of oxidative stress and can cause liver damage. A new drug has recently been in the news and seems to help greatly with this problem. The drug is called Triferic. Triferic mimics the way iron is absorbed into the body naturally. The absorption gradually goes to the body’s bone marrow and helps to maintain levels of hemoglobin. Triferic is still in the trial stages with 3 successful trials done so far. It very well may become an integrated treatment for those with CKD. (Glatter, 2013)
A patient with sickle cell has inherited the condition from both parents, and it all starts in the hemoglobin. Hemoglobin is “an iron-containing protein in red blood cells that reversibly binds to oxygen” (Reece, Urry, Cain, Wasserman, Minorsky, & Jackson, 2011). Obviously, hemoglobin is an important substance for oxygen to be transported in red blood cells. However, a patient with sickle cell has irregular hemoglobin cause by inherited genes. This “oxygen delivery” system cannot function properly because a gene
The heme prosthetic group, a protoporphrin IX ring structure with an iron atom ion the ferrous (Fe2+) oxidation state exist in both in myoglobin and he...
Iron comes from the Latin word ferrum. From ferrum its symbol became Fe. The atomic number of iron is 26, and its atomic weight is 55.845. Iron is a magnetic, bendable, shiny white metallic element.
In this experiment, we determined the isotonic and hemolytic molar concentrations of non-penetrating moles for sheep red blood cells and measured the absorbance levels from each concentration. The results concluded that as the concentration increased the absorbance reading increased as well. A higher absorbance signifies higher amounts of intact RBCs. The isotonic molar concentration for NaCl and glucose is 0.3 M. The hemolysis molar concentration for NaCl and glucose is 0.05 M. Adding red blood cells to an isotonic solution, there will be no isotonic pressure and no net movement. The isotonic solution leaves the red blood cells intact. RBC contain hemoglobin which absorbs light, hemoglobin falls to the bottom of the tube and no light is absorbed. Determining the isotonic concentration of NaCl and glucose by finding the lowest molar concentration. In contrast to isotonic molar concentration, hemolysis can be determined by finding the
Diabetes Mellitus is a chronic health condition in which the level of glucose in the blood is higher than usual. Type 1 diabetes occurs when the pancreas does not create enough insulin and type 2 diabetes occurs when insulin is produced, but is not adequate in lowering blood glucose levels or there is resistance to the insulin (Edwards, 2007, p. 9). Diabetes mellitus is the leading cause of end-stage kidney disease, foot and leg amputations, and new cases of blindness in the United States (Ignatavicius & Workman, 2010, p. 1465-66). People with type 1 diabetes are required to take insulin to manage their glucose levels. People with type 2 diabetes are usually prescribed oral medications such as sulfonylurea agents, meglitinide analogues, or biguanides to help control their glucose levels. Twenty to 30% of people with type 2 diabetes require insulin therapy as well (Ignatavicius & Workman, 2010, p. 1471). In addition to medication therapy, diet and weight control can help manage both type 1 and type 2 diabetes. Because diabetes mellitus can cause such severe complications, it is important that people with diabetes understand the importance of certain health and lifestyle choices, such as their diet and weight to manage their disease. Patients with diabetes mellitus should pay special attention to the amount of carbohydrates, protein, fat, and minerals that are included in their diet. Monitoring these components of their diet, along with weight management, can help control their diabetes mellitus.
Diabetes mellitus is a syndrome which causes relative or absolute insulin deficiency and characterized by hyperglycemia. The most common type is Type II Diabetes Mellitus. Metformin which is a biguanid group drug is the first line treatment for diabetes mellitus. Hypoglycemia does not usually occur with metformin and other advantages are the lower incidence of weight gain. It is mainly absorbed in intestine inhibits the hepetia gluconeogenesis and increases insulin sensitivity. Metformin is contraindicated in patients with hepatic, renal, heart and respiratory failure.
Zinc is present in all body tissues and fluids, with a total content ranging from (1.5-2.5gm) [8]. It has a key role in the normal physiology of the human body with various functions as a catalytic and structural component of various proteins[9]. Furthermore, It works as an antioxidant, anti-inflammatory agent and signaling mediator contributing to its vital roles in immunity, wound healing, and tissue repair.[10, 11]
This experiment consists of titrating the ferrous ion with permanganate ion to study the oxidation-reduction reaction. The ions react in acidic solution to give ferric ion and a reduced ionic form of manganese. All the reactants and products except permanganate ion are weakly colored, whereas permanganate is a very intensely colored ion. Then a solution of permanganate is removed as long as there is a ferrous ion present to react with it. But as soon as the entire ferrous ion has been oxidized, the next small portion of added permanganate colors the solution. The first appearance of a permanent pink color indicates the endpoint of the experiment. From the titration it will be able to calculate the percentage of iron in the sample from the data.