I just need a clear explanation why some metabolites are upregulated or downregulated in the presence of a xenobiotic compound?
I do want to know the general mechanism though. Like example, a specific compound is metabolized by the control but in the presence of a xenobiotic compound, this same compound cannot be metabolized anymore. I want to know the mechanism of regulation of metabolism, if you have any idea on that. Thank you.
since a xenobiotic is not normally found in the body normally it affects the body by various ways by affecting various neurotransmitters for eg in case of strontium chloride commonly used in making roads in whole europe,or from subterranean waters or by different ways can enter food chain through live stock and get absorbed and some investigations carried out show it affects the various neurotransnitters like histamine,serotonin,acetyl choline catechlamine levels with upregulating serotoning while downregulating histamine and catecholamines by affecting the H-P-A axis and affe ting the full neuroendocrine system and acetylcholine and acetylcholinesterase and this is just one example m,many other pesticides which are used in crops zre consumed in vegetablezs and food and some of them are passed by pregnant women to their fetuses and result in teratogenicity etc etc.
Thank you for the answer. I do want to know the general mechanism though. Like example, a specific compound is metabolized by the control but in the presence of a xenobiotic compound, this same compound cannot be metabolized anymore. I want to know the mechanism of regulation of metabolism, if you have any idea on that. Thank you.
i will give you a reverse exaple for example human beings cant digest certain oligosaccharides which certain bacteria can do but in human gut they use the enzymes of the host and hence the probiotic effect is used to treat obesity as certain gut bacteria are producing lipopolysaccharides and endotoxins and in gut the use of this pathway or change in metabolism by bacteria has been the explanation of certain obesities so the example i gave you of strontium the change in acetylcholinesterase by the xenobiotic effect will change metabolism in RBC'S aswell as the entire neuroendocrine system affecting the synthesis of neurotransmitters.
In general terms, a xenobitic may interact with a protein or multiple proteins, DNA or RNA and act as an inhibitor or activator of their biological functions. Depending on the nature of the target or targets, it will have biological ramifications which will include (but not limited to) over- or underproduction of "metabolites". But of course, metabolite concentrations are only a portion of what may be effected.
I hope the above is general enough! ;)
P.F. Zabrodskii, V.G. Lim, I.H. Yafarova. ACTIVATION OF Р-450-DEPENDED MONOOXYGENASES CHANGE IMMUNOTOXICITY OF PHOSPHOROORGANIC COMPOUNDS DEPENDING ON THEIR METABOLISM CHARACTER. Saratov Journal of Medical Scientific Research. 2010. 6(1). P. 46-48.
[Changes in the toxicity and immunotoxity of tetrachloromethane and carbophos under the action of 2,4,6-triphenyl-4H-selenopyran and their connection with cytochrome P-450 dependent monooxygenase system].
Zabrodskiĭ PF, Drevko BI, Mandych VG, Germanchuk VG, Balashov SV, Kuz'min AV.
Eksp Klin Farmakol. 2008 Nov-Dec;71(6):42-4. Russian.
PMID: 19140516 [PubMed - indexed for MEDLINE]
Eksp Klin Farmakol. 2008 Nov-Dec;71(6):42-4.
[Changes in the toxicity and immunotoxity of tetrachloromethane and carbophos under the action of 2,4,6-triphenyl-4H-selenopyran and their connection with cytochrome P-450 dependent monooxygenase system].
[Article in Russian]
Zabrodskiĭ PF, Drevko BI, Mandych VG, Germanchuk VG, Balashov SV, Kuz'min AV.
Abstract
It is established in experiments on noninbred rats that 2,4,6-triphenyl-4H-selenopyrane (peroral administration in a dose of 0.8 mg/kg during 3 days) induces cytochrome P450, thus increasing the toxicity and immunotoxicity of carbon tetrachloride (metabolized via "lethal synthesis"), and reduces the analogous effects of carbophos, the biotransformation of which proceeds via the formation of low-toxicity and nontoxic metabolites.
Inhibition of cytochrome P-450 with 2-diethylamino-ethyl-2,2-diphenylpropylacetate (SKF-525A) reduces immunotoxicity of chlorinated carbohydrates.
Zabrodskii PF, Mandych VG, Germanchuk VG.
Bull Exp Biol Med. 2006 Sep;142(3):324-6. English, Russian.
PMID: 17426840 [PubMed - indexed for MEDLINE]
Stimulation of immunotoxicity of chemicals metabolizing in vivo into highly toxic compounds by the monooxygenase system inductors.
Zabrodskii PF, Troshkin NM, Mandych VG.
Bull Exp Biol Med. 2004 Oct;138(4):369-71.
PMID: 15665947 [PubMed - indexed for MEDLINE]
Related citations
Bull Exp Biol Med. 2004 Oct;138(4):369-71.
Stimulation of immunotoxicity of chemicals metabolizing in vivo into highly toxic compounds by the monooxygenase system inductors.
Zabrodskii PF1, Troshkin NM, Mandych VG.
Author information
Abstract
Oral treatment of experimental random-bred albino rats with inductors of the monooxygenase system phenobarbital (50 mg/kg) and benzenal (70 mg/kg) for 3 days until acute poisoning with toxins (methanol, ethylene glycol, and dichloroethane in doses of 1.0 LD50) metabolizing in the body to compounds with higher toxicity (phenomenon of lethal synthesis) increased immunotoxicity of these inductors.
PMID: 15665947 [PubMed - indexed for MEDLINE]
In vitro effects of alcohols and their metabolites on antibody-forming activity of T and B lymphocytes.
Zabrodskii PF, Kirichuk VF, Osipov OV.
Bull Exp Biol Med. 2002 Mar;133(3):258-60.
PMID: 12360346 [PubMed - indexed for MEDLINE]
Related citations
Article: P.F. Zabrodskii, Serov V.V. Increased monooxygenase system inductors immunotoxicity methanol. Reports of the Academy of Military Sciences of RF. 2007. N 27. P. 56-58.
P.F. Zabrodskii, Serov V.V.
Book: П.Ф. Забродский, В.Г.Мандыч. Иммунотоксикология ксенобиотиков. Саратов, СВИБХБ. 2007. 420 p. P.F. Zabrodskii, V.G.Mandych. Immunotoxicology of xenobiotics. Saratov, Saratov Military Institute of Biological and Chemical Safety, 2007. 420 p.
П.Ф.Забродский, В.Г.Мандыч, P.F.Zabrodskii, V.G.Mandich
[Show abstract]
Saratov , Saratov Military Institute of Biological and Chemical Safety edited by P.F.Zabrodskii, 01/2007; Saratov Military Institute of Biological and Chemical Safety., ISBN: 978-5-91272-254-7
Example: Arachidonic acid is not seen in control but upon exposure to an antibiotic, the case showed high levels of arachidonic acid in its system.
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