A question about the effects of detoxification of xenobiotics on the example of ethanol
In this article, we provide you some Questions on the Detoxification of Xenobiotics, which getting some Effects & also this article contains some Questions on the example of ethanol. In Detoxification of Xenobiotics, Metabolism of Xenobiotics is for foreign bodies only. The overall mechanism of detoxification of Xenobiotics is to increase the water solubility (polarity) of toxic products and thus facilitate their excretion from the body mostly in urine and also through bile and feces. In Detoxification of Xenobiotics, Xenobiotic is a term used to describe chemical substances that are foreign to animal life and thus includes such examples as plant constituents, drugs, pesticides, cosmetics, flavorings, fragrances, food additives, industrial chemicals, and environmental pollutants. Just as wastes from normal metabolic processes are excreted in the urine, feces, and exhaled air, xenobiotics and their metabolites are also excreted from the kidneys, liver, and lungs. Chemicals that are rapidly eliminated may have limited phase I metabolism. In Detoxification of Xenobiotics, The term detoxification means that all the biochemical processes, whereby noxious substances are rendered less harmful and are more easily excreted in the urine.
Now Here are having some Questions on Detoxification of Xenobiotics – Effects & Questions on the example of ethanol.
If the patient receives large amounts of ethanol, this can lead to cirrhosis. Why?
It appears that necrosis is due to an inability to compensate for increased oxygen use to increase blood flow. The hypothesis that mitochondrial damage is the cause of liver cell damage is thought to be less important in the pathogenesis of necrosis. The shift in the redox state during the alcohol-fed state. Alcohol metabolism leads to changes in the central lobular region of the liver in which alcohol is fed. There is a highly reactive intermediates that are important in the pathogenesis of liver damage due to the induction of isozyme cytochrome P450 IIE1 by alcohol ingestion. This mechanism is enhanced by diets high in polyunsaturated fatty acids.
Oxidative metabolism of ethanol is affected by intracellular signaling pathways and causes leading to fat accumulation, fibro-genesis, and activation of innate and adaptive immunity and damages transcriptional control of many genes. Acetaldehyde is known to be toxic to the liver and reduces lipid homeostasis, reducing peroxisome proliferator-activated receptors, and enhancing sterol regulatory element-binding protein activity through AMP-activated protein kinase (AMPKase) -dependent mechanisms. AMPKase activation by ROS regulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehyde resulting from lipid peroxidation induce collagen synthesis by the ability of the protein to form tubules that activate change-factor-dependent-dependent and independent prophylogenic pathways in activated hepel stellate cells (HSCs). Also, activation of innate and adaptive immunity in response to ethanol metabolism plays an important role in the development and progression of ALD. Acetaldehyde changes the intestinal barrier and promotes the translation of lipopolysaccharide (LPS) by disrupting tight and adjacent junctions in the human colonic mucosa. Acetaldehyde and LPS Kupffer induce cells to release ROS and pro-inflammatory cytokines and chemokines that contribute to the infiltration of Neutrophils.
Consumption of a large amount of alcohol can inhibit the natural killer cells which are cytotoxic to HSCs and has an anti-fibrotic function in the liver. Ethanol metabolism can also interfere with cell-mediated adaptive immunity by impaired proteasome function in macrophages and dendritic cells, and result in altered allogenic antigen presentation. Then acetaldehyde and ROS play a role in alcohol-related carcinogenesis due to the formation of DNA adducts which is prone to mutations and hinders DNA methylation, synthesis, and repair, leading to increased NCC susceptibility.
Alcohol consumption causes liver diseases which are known as alcoholic liver disease (ALD) because alcohol is extracted by alcohol dehydrogenase (ADH) which makes a large ethanol metabolic system. Microsomal ethanol oxidation system (MEOS) has a cytochrome P450 enzyme (CYP) which is a major and important component of MEOS. Cytochrome P450 2E1 (CYP2E1) in MEOS is one of the most ROS (Role of stress) generators in the liver which is thought to contribute to alcoholic liver disease. In Human Cytochrome – CYP 2A6 and CYP2A5 are also alcohol-induced.
- Parenchymal Dystrophy, Hyaline-drop & Hydropic Dystrophy
- central and peripheral organ of Hematopoiesis – Structure & function
- Hypothyroidism in Newborns: Diseases of the Thyroid Gland in Children
- Human endocrine system: anatomical and physiological reference
- Histology: Research Methods, Structure of Tissues, and Cells
In Detoxification of Xenobiotics, if the patient receives moderate amounts of ethanol for a long time, this leads to obesity of the liver. Why?
In hepatocytes, free fatty acids (FFAs) can be metabolized by oxidation to oxidation for the generation of ATP or by esterification to produce triglycerides which can either stored in lipid droplets into hepatocytes and released in blood as a very low-density lipoprotein particles. A free fatty acid is released into the blood. FFAs are derived from three different sources: (DNL), from dietary sources, carbohydrates, or amino acids, and release from lipids stored in VAT or subcutaneous fat. Above a rate hydrolyzed from hepatic fat, or lipoprotein from liposis of adipose tissue, which can be taken up by adipose tissue, is up to 60% of FFA, 25% from DNL (de novo Lipogenesis), and 15% from dietary sources.
During the fasting state, hepatic FFA is distributed with an increase in portal supply after meals by systemic circulation. After released into the portal circulation, FFA is taken up by hepatocytes mainly through long-chain fatty acid synthetase activity conferred by members of the FA transporter protein family. Once within the hepatocyte, FFAs bind to enzymes in the form of fatty acyl-coase to form hepatic triglycerides and induce insulin-induced glucose deficiency and induce intracellular inflammation. However, high levels of FFA can induce intracellular inflammation and IR without converting it to fatty acyl-CoS.
De-novo Lipogenesis (DNL): – DNL is a process in which fatty acids where synthesizing with the help of acetyl‐CoA subunits which can be produced by different pathways into the cell which is the most common carbohydrate catabolism.
Excess glucose is released into the hepatic acetyl-COA pool by glycolysis of carbohydrates for the production and storage of triglycerides. DNL provides 5% –10% of the liver triglyceride pool in the fasting state, with IR (Insulin Resistance) contributing to an increase in individuals. DNL (de novo Lipogenesis) is modified by total energy intake, fat to carbohydrate fat ratio, and glucose and insulin concentration. Thus, hyperinsulinemia and hyperglycemia occurring with IR cause an imbalance in lipid input to promote output and hepatic steatosis. The strong suppressive effect of insulin on hormone-sensitive lipase, the main regulator of FFA release from VAT (adipocytes), is impaired in IR resulting in an increased flow of FFA. Hyperinsulinemia leads to the decomposition of transcription factors controlling DNL and inhibition of FFA further-oxidation, which further promotes liver fat accumulation. However, it has not yet been determined whether adipose arises from adipose tissue of IR and skeletal muscle or changes in liver insulin signaling. Despite the role of VAT in liver fat accumulation through direct liver exposure to excess FFA within the portal circulation, liver fat is also involved in IR within the absence of VAT, possibly by secretion of hepatocytes. Fat accumulation of the liver is occurring thanks to defects in insulin suppression of glucose production and serum FFA independent of obesity in normal men. liver fat is independent of BMI and intestinal shortness. Metabolic syndrome was more strongly associated with VAT at lower levels of obesity, and with liver fat at higher obesity levels, independent of one another and overall fat. The accumulation of hepatic fat is a major determinant in Type 2 Diabetes (T2D), which subsequently contributes not only to the liver steatosis level, but also to progressive liver damage in NASH, fibrosis, cirrhosis, and HCC.
Adipocyte is similar to inflammation of adipose tissue after lipid accumulation, the subacute inflammatory response in the liver may be induced by hepatic steatosis, which involves oxidative stress in the endoplasmic reticulum (ER). ER stress in liver and adipose tissue is induced by nutrient fluctuations and excess lipid levels in genetically or HFD (high-fat diet) – induced obese mice. The subacute provides an environment conducive to HCC development by promoting cell growth kinetics and DNA damage coupled with inflammation, IR, hepatic steatosis, oxidative stress, and impaired adipocytokine ratios. Also, hepatocyte apoptosis induction, inflammatory cell invasion and activation, and fibrogenesis leads to cirrhosis, and possibly to NASH-related HCC (Hepatocellular carcinoma).
FA beta-oxidation, which occurs in liver mitochondria, may be attenuated by increased FFA loads in NAFLD, resulting in the generation of reactive oxygen species. The resulting oxidative stress leads to the initiation and progression of liver injury, inflammation, and fibrosis. Inadequate mitochondrial function with structural abnormalities such as increased mitochondria, loss of mitochondrial Christ, and presence of paracystrolin inclusion bodies have been observed at all successive stages leading to NASH.
Why do the effects of the same xenobiotic produce different effects?
Xenobiotic is a chemical compound, for example, a pesticide, medicine, and carcinogen that is foreign to the biological systems of a living organism. Human toxicity occurs when the xenobiotic compound concentration increases beyond the level of resistance (metabolism) of the human body. Natural compounds can also act as a xenobiotic if they are taken up by organisms that are unable to digest and grow it from the body. The following are reports on human toxicity due to two such toxic compounds.
Effects of xenobiotics: –
· Xenobiotic metabolism can cause cell injury, immunological injury, or damage, or cancer.
· Cell injury (cytotoxicity) can be severely sufficient in cell death.
· These macromolecular targets include DNA, RNA, and protein.
· A xenobiotic’s reactive species can bind to the protein, altering its antigenicity.
· The resulting antibodies may then damage the cell bisexual immunologic mechanisms that largely affect abnormal cellular biochemical processes.
· The reaction of the active species of the chemical carcinogenesis DNA is of great importance in chemical chemistry.
· Some chemicals (eg, benzo [α] pyrenes) are required in endoplasmicromatics to become carcinogenic by monooxygenases (they are thus called indirect carcinogens).
· The products of the action of some monocarboxynsone are epoxides, some procarcinogen substrate.
· Epoxides are highly reactive and mutagenic carcinogenic or both.
· Epoxide hydrolase-like cytochrome P450acts on these compounds, converting them to very little reactive dehydration.
the same xenobiotic produces different effects: – Xenobiotics can produce different effects because they will show the effect with their reactant and other bio-molecules at different palaces. Same Xenobiotics can react with another substance: – like if at a one xenobiotic has a different environment and different reactants then it’s result will be different from another environmental condition.
How blood pressure and regulation of water-salt metabolism depend on each other.
Sodium chloride, commonly called dietary salt, is essential for our body. But a high salt intake can increase blood pressure, which can damage the body in many ways over time. High blood pressure has been linked to heart disease, stroke, kidney failure, and other health problems.
The kidneys use osmosis to remove excess water from your blood. This process uses a delicate balance of sodium and potassium to draw water from the bloodstream to a collecting channel on a wall of cells that leads to the bladder. Eating salt increases the amount of sodium in your bloodstream and reduces the ability of your kidneys to remove water, which causes a delicate balance. The resulting excess fluid results in high blood pressure and additional pressure on the delicate blood vessels leading to the kidneys. Over time, this extra stress can damage the kidneys – known as kidney disease. This reduces their ability to filter out unwanted and toxic waste products, which then begin to build up in the body. If kidney disease is omitted and blood pressure does not decrease, the damage can lead to kidney failure. If kidneys are no longer able to filter the blood and the body gradually becomes toxic by its own toxic waste products. If you have high blood pressure and are being treated with a diuretic drug, this causes the kidneys to remove excess fluid from the bloodstream. Due to sodium in salt can counteract these effects, reducing salt intake can occur more effective blood pressure medication.
Hypertension (High Blood Presser) and diabetes patients must maintain regulation of their ionic i.e. calcium and magnesium levels and sodium and potassium levels are also important in patients with heart-related problems. Magnesium and arrhythmias, ion balance in heart failure, diabetes, ischemic stress, and oxidative stress in cardio-myopathy of magnesium deficiency, magnesium, and Roles of potassium is involved in the bone. Metabolism & aging populations and play an important role in electrolyte and ion balance in blood pressure (hypertension). Maintaining the homeostasis of potassium and magnesium is important in all of these issues and various treatments that affect the retention of these ions were discussed. Hallmark’s studies, i.e., antihypertensive and lipid-lower treatment to prevent heart attack trials and the study of left ventricular dysfunction; have provided insights into the treatment of patients with cardiac and progressive heart failure. The availability of potassium- and magnesium-sparing diuretics for use in these studies and these disorders provides relevant treatment approaches.