Carbonyl Toxification Hypothesis of Biological Aging
Alvaro Macieira-Coelho in Molecular Basis of Aging, 2017
The physiological concentration of DMcarbonyls, measured as thiobarbituric acid reactive substance (TBARS), are in the range of 0.3 to 5.0 nmol/mL in normal human plasma,30 whereas the concentration of protein carbonyls are about 3.0 nmol/mg protein in healthy humans.2,30 Various types of free radical damage, e.g., ionizing radiation, metal-catalyzed oxidation, and oxidation by ozone or nitrogen oxides, may cause a direct and acute effect to biomolecules and increase cellular carbonyls, which may then reinforce carbonyl toxification in vivo. Lipid peroxidation was reported to increase progressively with advancing age, such that TBARS values of liver, brain, kidney, and testis from old rats are significantly higher than those of younger ones.74 Likewise, Yagi and colleagues have demonstrated that the plasma TBARS values of diabetic patients are higher than those of controls, i.e., 5.5 vs. 3.5 nmol/ml.75 The carbonyl toxification hypothesis of aging is also compatible with the finding that animals with a high metabolic rate have a shorter life span, probably because they also have an increased rate of carbonyl production.
Historical Notes
Albert A. Kurland, S. Joseph Mulé in Psychiatric Aspects of Opiate Dependence, 2019
The clinical experiences with methadone de-toxification paved the way for developments leading to the introduction of methadone maintenance as a treatment form by Dole and Nyswander.62 The extensive application of this treatment modality has indicated that many of. these patients, despite such maintenance, still resort to alcohol abuse and multiple drug consumption. The clinician has also found that the use of psychotropic drugs, namely, antipsychotic drugs, antidepressants, and anxiolytics are required to cope with exacerbations of dysphoric states from time to time despite their methadone maintenance.109–111
A Comparison of African American and Cuban American Adolescent Juvenile Offenders: Risky Sexual and Drug Use Behaviors
Mario R. De La Rosa, Lori K. Holleran, Shulamith Lala Ashenberg Straussner in Substance Abusing Latinos, 2012
Subsequent to informed assent and parental consent, assessment measures were administered orally to facilitate accurate reporting, full completion, and to compensate for any difficulties in reading comprehension. Each interview lasted approximately 90 minutes. Baseline assessments were administered one week after participants’ admission and clearance from treatment staff that detoxification was adequately completed. This procedure was followed to minimize the effect of de-toxification or withdrawal factors on test performance and to maximize the accuracy of responses.
Association of Activity Altering Genotypes - Tyr113His and His139Arg in Microsomal Epoxide Hydrolase Enzyme with Esophageal Squamous Cell Carcinoma
Published in Nutrition and Cancer, 2019
Sumaiya Nabi, Gulzar Ahmad Bhat, Beenish Iqbal, Mohd Maqbool Lone, Ghulam Nabi Lone, Maroof Ahmad Khan, Nazir Ahmad Dar
Microsomal epoxide hydrolase (mEH, also EPHX1) is an important xenobiotic metabolizing enzyme with typical features like metabolizing a diverse array of toxicants and carcinogens (15–17), broad tissue distribution and substrate specificity (18–20), and inducibility by foreign compounds (21,22). mEH is primarily involved in the detoxification of potentially genotoxic and carcinogenic epoxides and their intermediates to corresponding less reactive (nontoxic) vicinal diols (16,17). These epoxides are present in diet or generated within the body from dietary and environmental toxins like benzopyrenes, polycyclic aromatic hydrocarbons (PAHs), and nitrosamines (23,24). However, in some circumstances mEH is involved in the toxification of its substrates, with potentially fatal outcome. Such a dual role of mEH is demonstrated by bio-activation of the PAH, benzo(a)pyrene present in the cigarette smoke (25,26). For example, mEH in collaboration with cytochrome-P-450 (CYP) converts benzo(a)pyrene to more reactive intermediate, benzo(a)pyrene-7,8-dihydrodiol 8,9-epoxide (Benzo(a)pyrene diolepoxide, BPDE) which displays higher mutagenic and carcinogenic potential than its substrate.
Metabolism of the areca alkaloids – toxic and psychoactive constituents of the areca (betel) nut
Published in Drug Metabolism Reviews, 2022
Although knowledge of AN consumption and the associated psychoactive effects and health deficits are not new, there is still much to be learned about how the intriguing small molecule alkaloids (e.g. arecoline) abundant in this nut are handled by drug metabolism machinery in the human body. In this comprehensive review, metabolism information was initially extracted from in vitro work in tissue fractions and cells and then from in vivo PK studies in animals and humans. Major pathways of arecoline elimination include de-esterification, GSH conjugation, N-oxidation, nitrosamine conversion, and surprisingly carbon–carbon double-bond reduction that results in the formation of N-methylnipecotic acid – a major urinary metabolite of arecoline in mice (Giri et al. 2006) and humans (Hu et al. 2010). Furthermore, major toxification steps include metabolism to an N-oxide derivative by FMO and nitrosamine formation in the presence of nitrite (Figure 2). Downstream metabolism of metabolites may also contribute to AN-induced toxicity, although this remains speculative.
Effects of Phyllanthus amarus PHYLLPROTM leaves on hangover symptoms: a randomized, double-blind, placebo-controlled crossover study
Published in Pharmaceutical Biology, 2019
Annie George, Jay K. Udani, Ashril Yusof
Chronic ethanol intake (i.e., several years of heavy alcohol use in humans, several weeks or months in experimental animals) enhances the damaging consequences of inflammatory responses through a variety of mechanisms. It would have been expected that, in the presence of alcohol detoxification, AST would have increased as a number of liver cells may have been damaged; however, in this case, there was no significant difference in AST between the groups. Another biomarker that is commonly associated with inflammation is CRP, which in this study did not show group difference, whereas in another study, supplementation of the medicinal herb Ginkgo biloba L. (Ginkgoaceae) was shown to reduce CRP levels while improving total antioxidant levels in serum ischaemic stroke patients (Thanoon et al. 2012). In a study on hangover symptoms, decreased levels of CRP were associated with reduced hangover symptoms; however, liver enzymes (AST and ALT) were not reduced (Wiese et al. 2004). It is possible that the alcohol toxification in this study was not chronic enough to warrant an intense inflammatory reaction.
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