Gastrointestinal Function and Toxicology in Canines
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems [29–34,123,136,148,202,230,236,263,273,286,296,301,316,364,410]. More generally, xenobiotic metabolism (from the Greek xenos, “stranger” and biotic, “related to living beings”) is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism’s normal biochemistry, such any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds (although in some cases the intermediates in xenobiotic metabolism can themselves cause toxic effects). The study of drug metabolism is called pharmacokinetics.
Xenobiotic Biotransformation
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
A understanding of xenobiotic biotransformation is one of science’s most notable examples of the practical applications and societal benefits derived from basic research. Studies on xenobiotic biotransformation have defined the roles of genetics, age, diet, and various environmental factors, and have demonstrated the importance of induction and inhibition in xenobiotic/drug exposures in individual sensitivity to chemicals [see Conney (1982) for numerous examples]. Perhaps the most important concept derived from research on xenobiotic biotransformation is that electrophiles generated during the process initiate toxicity and carcinogenicity by binding to critical cellular nucleophiles (Miller and Miller, 1981b). This concept has been the driving force behind a significant portion of research in carcinogenesis, toxicology, and pharmacology and has been utilized to assess the toxic and carcinogenic potential of drugs and xenobiotics [see Hammons et al. (1985) for an example] and to design chemotherapeutic regimens with enhanced tissue selectivity and drug analogs with reduced toxicity. Studies on the mechanisms of genetic control of the Ah locus (Nebert and Gonzalez, 1987) have contributed to current concepts on genetic regulation of enzyme and cellular function and to understanding the genetic basis for adaptive responses that provide cells’ selective survival advantage in response to environmental insult.
Pesticides and Chronic Diseases
William J. Rea, Kalpana D. Patel in Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
The behavior and fate of pesticides in the environment will determine their impact on both humans and nontarget organisms. Biochemical biomarkers are increasingly used in ecological risk assessment to identify the incidence of exposure to and effects caused by xenobiotics. This study was undertaken to investigate the potential toxic effect of a locally produced insect powder called “Rambo” (which contains 0.6% permethrin) on nontarget organisms exemplified with albino rats. The results obtained showed that glutathione S-transferase (GST) activity in the newly weaned rats (NWR) and middle-aged rats (MAR) groups were found to increase significantly (p < 0.05) in the liver homogenates at the concentrations used (1%, 5%, and 10%) compared with their parallel controls. In the plasma and brain homogenates, a decrease in GST activity was observed; this decrease was significant (p < 0.05) in the brain homogenates, but in the blood plasma, the decrease in GST activity was not significant (p > 0.05).
Syzygium Aromaticum Alleviates Cerium Chloride-Induced Neurotoxic Effect In The Adult Mice
Published in Toxicology Mechanisms and Methods, 2019
Yamina Kadri, Riadh Nciri, Sana Bardaa, Noura Brahmi, Saidi Saber, Abdel Halim Harrath, Waleed Aldahmash, Saleh Alwasel, Mohamed Mohany, Abdelfatteh El Feki, Mohamed Salah Allagui
The environmental pollution caused by xenobiotic can deteriorate health of the living being (Waliszewski et al. 1996; Lippmann 2000). Among xenobiotics, Cerium is one of the rare earth elements of chemical formula (Ce) with an atomic number of 58. It is the most abundant element of this group in the earth's crust (average concentration of 66 ppm) and represents on its own more 50% of the lanthanide family (Rudnick and Fountain, 1995). For comparison, cerium is more abundant than tin, cobalt, or lead (Wang, Liang, Zhang, and Li, 2014). Cerium causes toxicity in case of high dose exposure. It is found that cerium is implicated in various forms of oxidation when present in its trivalent form (Ce3+) and tetravalent form (Ce4+) (Dahle and Arai 2015). The cerium contamination could be caused by Industrial waste, anthropogenic, and atmospheric nuclear explosion (Wen et al. 2000; Jakupec et al. 2005; Gupta et al. 2006). Because of its widespread use, cerium is accumulated in the environment and is transferred to humans through food chain (Gupta et al. 2006). Intravenous injection of CeCl3 in rats causes blood (serum and erythrocytes) and organs (liver, kidney, bones and lungs) toxicity (Nakamura et al. 1997). However, only few studies have evaluated the toxicity of cerium chloride in the brain (Zhao et al. 2011).
SNP’s in xenobiotic metabolism and male infertility
Published in Xenobiotica, 2020
Neslihan Hekim, Mohamed Ali Gure, Asli Metin Mahmutoglu, Sezgin Gunes, Ramazan Asci, Ralf Henkel
Male germ cells are especially sensitive to xenobiotic action that leads to significant sperm DNA damage and increase the incidence of sperm aneuploidy (Pacchierotti and Eichenlaub-Ritter, 2011) regardless route of exposure. This fact is supported by the studies performed on coke oven and factory workers exposed to PAH and organic molecules, respectively. Additionally, advances in chemotherapeutic agents and molecular medicine becoming more efficient for the treatment of men in reproductive age. Environmental estrogens, smog and organochlorides have also been suggested to be aggressive promoters of sperm DNA damage (Simon et al., 2017) and lead to alterations in sperm production, altering hormonal balance or sexual function (Stearns and Turek, 2013). Xenobiotics could reach toxic levels and thereby strongly affect the organism if they are not metabolized. Most of the xenobiotics undergo enzymatic biotransformation and many factors have an impact on the activities of these enzymes including genetic variations.
Formaldehyde toxicity reports from in vitro and in vivo studies: a review and updated data
Published in Drug and Chemical Toxicology, 2022
Letícia Bernardini, Eduardo Barbosa, Mariele Feiffer Charão, Natália Brucker
Dahlgren and Talbott (2018) observed developing asthma from repeated occupational exposure to high levels of FA in hairdressers exposed to hair smoothing products. The effects of occupational exposure to FA in salon workers, with different exposure levels, also was investigated by Barbosa et al. (2019). This study indicated that FA plays a part in increasing global DNA methylation, although the specific mechanisms remain unknown. These results suggested that even low levels of exposure may contribute to epigenetic changes in individuals occupationally exposed to FA. Peteffi et al. (2016) also evaluated workers of beauty salons and found an increase in genotoxicity biomarkers due to the use of hair straightening products containing FA. Furthermore, the toxicity effect of xenobiotics exposure depends on individual susceptibility. Thus, gene polymorphisms have a critical role in individual susceptibility and could influence risk factors associated with pathologies (Zhang et al. 2013, Zendehdel et al. 2016).
Related Knowledge Centers
- Drug Metabolism
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- Carcinogen
- Cytochrome P450
- Glutathione
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- Food Additive