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Glyoxalase System
The glyoxalase system is a set of enzymes that carry out the detoxification of methylglyoxal and the other reactive aldehydes that are produced as a normal part of metabolism. This system has been studied in both bacteria and eukaryotes. This detoxification is accomplished by the sequential action of two thiol-dependent enzymes; firstly Lactoylglutathione lyase, glyoxalase І, which catalyzes the isomerization of the spontaneously formed hemithioacetal adduct between glutathione and 2-oxoaldehydes (such as methylglyoxal) into S-2-hydroxyacylglutathione. Secondly, Hydroxyacylglutathione hydrolase, glyoxalase ІІ hydrolyses these thiolesters and in the case of methylglyoxal catabolism, produces D-lactate and GSH from S-D-lactoyl-glutathione. This system shows many of the typical features of the enzymes that dispose of endogenous toxins. Firstly, in contrast to the amazing substrate range of many of the enzymes involved in xenobiotic metabolism, it shows a narrow substrate specificity ...
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Detoxification
Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of drug withdrawal during which an organism returns to homeostasis after long-term use of an addictive substance. In medicine, detoxification can be achieved by Poison#Decontamination, decontamination of poison ingestion and the use of antidotes as well as techniques such as Kidney dialysis, dialysis and (in a limited number of cases) chelation therapy. Many alternative medicine practitioners promote various types of detoxification such as Detoxification (alternative medicine), detoxification diets. Sense about Science, a UK-based charitable trust, determined that most such dietary "detox" claims lack any supporting evidence. The liver and kidney are naturally capable of detox, as are intracellular (specifically, inner membrane of mitochon ...
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Fisetin
Fisetin (7,3′,4′- flavon-3-ol) is a plant flavonol from the flavonoid group of polyphenols. It occurs in many plants where it serves as a yellow pigment A pigment is a powder used to add or alter color or change visual appearance. Pigments are completely or nearly solubility, insoluble and reactivity (chemistry), chemically unreactive in water or another medium; in contrast, dyes are colored sub .... It is found in many fruits and vegetables, such as strawberries, apples, persimmons, onions, and cucumbers. Its chemical formula was first described by Austrian chemist Josef Herzig in 1891. Sources Fisetin is a flavonoid synthesized by many plants such as the trees and shrubs of Fabaceae, acacias '' Acacia greggii'', and '' Acacia berlandieri'', parrot tree ('' Butea frondosa''), honey locust ('' Gleditsia triacanthos''), members of the family Anacardiaceae such as the '' Quebracho colorado'', and species of the genus '' Rhus'', which contains the sumacs. Along wit ...
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Advanced Glycation End-product
Advanced glycation end-products (AGEs) are proteins or lipids that become Glycation, glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease. Dietary sources Animal-derived foods that are high in fat and protein are generally AGE-rich and are prone to further AGE formation during cooking. However, only low molecular weight AGEs are absorbed through diet, and vegetarians have been found to have higher concentrations of overall AGEs compared to non-vegetarians. Therefore, it is unclear whether dietary AGEs contribute to disease and aging, or whether only endogenous AGEs (those produced in the body) matter. This does not free diet from potentially negatively influencing AGE, but potentially implies that dietary AGE may deserve less attention than other aspects of diet that lead to elevated Blood sugar level, b ...
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Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., (superoxide radical), OH ( hydroxyl radical) and (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the development of attention deficit hyperactivity disorder, cancer, Parkin ...
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Hyperglycemia
Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood glucose level indication Patients with diabetes are oriented to avoid exceeding the recommended postprandial threshold of 160 mg/dL (8.89 mmol/L) for optimal glycemic control. Values of blood glucose higher than 160 mg/dL are classified as 'very high' hyperglycemia, a condition in which an excessive amount of glucose (glucotoxicity) circulates in the blood plasma. These values are higher than the renal threshold of 10 mmol/L (180 mg/dL) up to which glucose reabsorption is preserved at physiological rates and insulin therapy is not necessary. Blood glucose values higher than the cutoff level of 11.1 mmol/L (200 mg/dL) are used to diagnose T2DM and strongly associated with metabolic disturbances, although symp ...
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Pyridoxamine
Pyridoxamine (PM) is one form of vitamin B6. Chemically it is based on a pyridine ring structure, with hydroxyl, methyl, aminomethyl, and hydroxymethyl substituents. It differs from pyridoxine by the substituent at the 4-position. The hydroxyl at position 3 and aminomethyl group at position 4 of its ring endow pyridoxamine with a variety of chemical properties, including the scavenging of free radical species and carbonyl species formed in sugar and lipid degradation and chelation of metal ions that catalyze Amadori reactions. Research Pyridoxamine can form fairly weak complexes with a number of transition metal ions, with a preference for Cu2+ and Fe3+. The 3'-hydroxyl group of pyridoxamine allows for efficient hydroxyl radical scavenging. Pyridoxamine inhibits the Maillard reaction and can block the formation of advanced glycation endproducts, which are associated with medical complications of diabetes. Pyridoxamine is hypothesized to trap intermediates in the forma ...
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Benfotiamine
Benfotiamine ( rINN, or ''S''-benzoylthiamine ''O''-monophosphate) is a synthetic, fat-soluble, ''S''-acyl derivative of thiamine (vitamin B1) that is approved in some countries as a medication or dietary supplement to treat diabetic sensorimotor polyneuropathy. Benfotiamine was developed in late 1950s in Japan. Uses Benfotiamine is primarily marketed as an over-the-counter drug to treat diabetic polyneuropathy. A 2021 review described two clinical trials with positive results for diabetic polyneuropathy and concluded that more research is needed. As of 2017, benfotiamine was marketed as a pharmaceutical drug in many countries under the following brand names: Benalgis, Benfogamma, Benforce, Benfotiamina, Biotamin, Biotowa, Milgamma, and Vilotram. It was also marketed in some jurisdictions as a combination drug with cyanocobalamin as Milgamma, in combination with pyridoxine as Milgamma, in combination with metformin as Benforce-M, and with thiamine as Vitafos. Adverse effects T ...
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Alagebrium
Alagebrium (formerly known as ALT-711, dimethyl-3-N-phenacylthiazolium chloride) was a drug candidate developed by Alteon, Inc. It was the first drug candidate to be clinically tested for the purpose of breaking the crosslinks caused by advanced glycation endproducts (AGEs), thereby reversing one of the main mechanisms of aging. Through this effect Alagebrium is designed to reverse the stiffening of blood vessel walls that contributes to hypertension and cardiovascular disease, as well as many other forms of degradation associated with protein crosslinking. Alagebrium has proven effective in reducing systolic blood pressure and providing therapeutic benefit for patients with diastolic heart failure. Mechanism Advanced glycation end-products (AGEs) are proteins that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney di ...
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Aminoguanidine
Pimagedine, also known as aminoguanidine, is an investigational drug for the treatment of diabetic nephropathy that is no longer under development as a drug. Pimagedine functions as an inhibitor of diamine oxidase and nitric oxide synthase. It acts to reduce levels of advanced glycation end products (AGEs) through interacting with 3-deoxyglucosone, glyoxal, methylglyoxal, and related dicarbonyls. These reactive species are converted to less reactive heterocycles by this condensation reaction. History Pimagedine was under development as a drug for kidney diseases by the pharmaceutical company Alteon (now known Synvista Therapeutics Inc.) that was founded in 1986. In 1987, Alteon acquired a license to intellectual property relating to AGE inhibition from Rockefeller University. In 1989, Alteon and Marion Merrell Dow Inc (MMD) entered into a joint development program for pimagedine. In 1992, Alteon licensed a patent from Rockefeller University relating to the use of pimagedine ...
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Bardoxolone Methyl
Bardoxolone methyl (also known as “RTA 402”, “CDDO-methyl ester”, CDDO-Me, and more formally methyl bardoxolonate) is an experimental and orally- bioavailable semi-synthetic triterpenoid, based on the scaffold of the natural product oleanolic acid. Pre-clinical studies indicate that the compound acts as an activator of the Nrf2 pathway and an inhibitor of the NF-κB pathway. A phase 3 clinical trial evaluating bardoxolone methyl for the treatment of chronic kidney disease (CKD) was terminated in October 2012 after patients treated with the drug were found to have experienced a higher rate of heart-related adverse events, including heart failure, hospitalizations, and deaths. An advisory committee meeting of experts voted unanimously that bardoxolone methyl was not effective in slowing the progression of chronic kidney disease in Alport syndrome and that its benefits did not outweigh its risks. A Complete Response Letter from FDA stated a similar opinion. Clinical ...
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Sulforaphane
Sulforaphane (sometimes sulphoraphane in British English) is a phytochemical within the isothiocyanate group of organosulfur compounds. It is produced when the enzyme myrosinase transforms glucoraphanin, a glucosinolate, into sulforaphane upon damage to the plant (such as from chewing or chopping during food preparation), which allows the two compounds to mix and react. Sulforaphane is present in cruciferous vegetables, such as broccoli, Brussels sprouts, and cabbage. Sulforaphane has two possible stereoisomers due to the presence of a stereogenic sulfur atom. The R-sulforaphane enantiomer occurs naturally, while the S-sulforaphane can be synthesized. Occurrence and isolation Sulforaphane occurs in broccoli sprouts, which, among cruciferous vegetables, have the highest concentration of glucoraphanin, the precursor to sulforaphane. It is also found in cabbage, cauliflower, Brussels sprouts, bok choy, kale, collards, mustard greens, and watercress. Research Alth ...
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Phenethyl Isothiocyanate
Phenethyl isothiocyanate (PEITC) is a naturally occurring isothiocyanate whose precursor, gluconasturtiin is found in some cruciferous vegetables, especially watercress. PEITC has been studied for its potential for chemoprevention of cancers, such as prostate cancer. In terms of biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ..., PEITC is produced from gluconasturtiin by the action of the enzyme myrosinase. References Isothiocyanates Phenyl compounds {{Cruciferous Biochemistry ...
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