Role of physiological factors in predicting the risk of oncological diseases on the basis of the polymorphism of the xenobiotic metabolism enzyme system

Суханов, В. В.; Piruzyan, L. A.

doi:10.1134/s0362119710060149

Cited by 2 publications

(1 citation statement)

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the elucidation of the potential toxicological mechanisms of Baifupian in rats, use of conventional research techniques such as histological and biochemical analyses may have certain disadvantages because: [1] multiple targets might be involved in its general toxic reactions; [2] the herb contains multiple chemical components, such as aconitine (Supporting Information, Figure 1A), mesaconitine (Supporting Information, Figure 1B), and hypaconitine (Supporting Information, Figure 1C); [3] there are biological variations in the absorption, distribution, metabolism, and excretion (ADME) of Baifupian; and [4] there is an existing polymorphism of drug metabolism enzymes . Alternatively, the metabolic profiling strategy enables us to identify the varying metabolites and related metabolic pathways in the complex regulatory network by monitoring many endogenous low-molecular-weight metabolites using liquid chromatography/mass spectrometry (LC–MS), followed by a combination of multivariate statistical techniques and pattern recognition techniques, such as principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). − Metabolomics has brought enormous opportunities for improved detection of toxicity and biomarker discovery .…”

Section: Introductionmentioning

confidence: 99%

Deciphering the Differential Toxic Responses of Radix aconiti lateralis praeparata in Healthy and Hydrocortisone-Pretreated Rats Based on Serum Metabolic Profiles

Tan

Liu

et al. 2012

J. Proteome Res.

View full text Add to dashboard Cite

Radix aconiti lateralis praeparata (Baifupian) has received great attention because of its excellent therapeutic effects as well as the associated adverse drug reactions. According to the traditional Chinese medicine (TCM) principle, Baifupian should only be used in patients with TCM "kidney-yang" deficiency pattern, a clinical state that can be mimicked by hydrocortisone induction in rats. This study aimed to decipher the differential toxic responses of Baifupian in healthy and hydrocortisone-pretreated rats based on serum metabolic profiles. Drug-treated rats received Baifupian intragastrically at the dose of 1.28 g/kg/day for 15 days. Serum metabolic profiles were obtained by using the LC-Q-TOF-MS technique. Our results show that Baifupian could induce severe toxicity in the heart, liver, and kidneys of healthy rats. These drug-induced toxic reactions were largely alleviated in hydrocortisone-pretreated animals. Changes of metabolic profiles in drug-treated healthy and hydrocortisone-pretreated rats were demonstrated, involving oxidative phosphorylation, amino acid and lipid metabolism as characterized by altered phosphate, betaine, and phosphatidyl choline. These metabolic alterations could be responsible at least in part for the differential toxic responses of Baifupian under various health conditions. This study provides a new paradigm for better understanding of the risks and limitations when using potentially toxic herbs in clinical applications.

show abstract

Section: Introductionmentioning

confidence: 99%

Deciphering the Differential Toxic Responses of Radix aconiti lateralis praeparata in Healthy and Hydrocortisone-Pretreated Rats Based on Serum Metabolic Profiles

Tan

Liu

et al. 2012

J. Proteome Res.

View full text Add to dashboard Cite

show abstract

Immune-hormonal imbalance in chemical cancerogenesis

Глушков¹

2022

Russian Journal of Immunology

View full text Add to dashboard Cite

The present article deals with experimental and clinical aspects of immuno-hormonal interactions in chemical carcinogenesis i.e., formation of DNA-adducts with chemical carcinogens as a trigger of tumor initiation; synthesis of specific antibodies as markers of human exposure to environmental carcinogens; immunomodulation of chemical carcinogenesis by the specific antibodies in experimental studies; interactions of antibodies against environmental carcinogens with endogenous steroid hormones in human carcinogenesis; immunological interference and inversion of immuno-hormonal interactions by the action of antibodies against environmental carcinogens; immune stimulation of tumor progression in cancer patients. It is shown that antibodies specific to estradiol and progesterone participate in regulation of serum estradiol and progesterone levels in healthy women. Excessive production of antibodies against benzo[a]pyrene is associated with impaired physiological balance between the levels of antibodies to estradiol and progesterone, thus causing disturbed physiological balance between serum estradiol and progesterone. Immuno-hormonal imbalance promotes tumor initiation, its growth and progression. The new approaches to the personalized cancer immunoprediction and immune prevention are discussed. Coordinated synthesis of antibodies against benzo[a]pyrene and estradiol seems to reflect production of DNA-adducts with genotoxic metabolic effects of these compounds manifesting as synergistic carcinogenic effects upon the target cells. Hence, simultaneously increased levels of serum antibodies against benzo[a]pyrene and estradiol in healthy people may be considered an immunological marker of high oncological risk and an reason to use of new immunoprotective tools against polycyclic aromatic hydrocarbons and phytoestrogens. However, ability of these antibodies to raise the blood serum levels of environmental carcinogens and endogenous estradiol, as shown in vitro and in vivo, excludes the opportunity for active cancer immune prevention. Usage of anticarcinogen vaccines aimed for induction of protective secretory antibodies is likely to further increase high levels of procarcinogenic serum antibodies against benzo[a]pyrene and estradiol, followed by additional enhancement of immuno-hormonal imbalance and promotion of carcinogenesis. Development of probiotics transduced with genes encoding human antibodies against environmental carcinogens may present an alternative approach to cancer immune prevention. The antibodies produced by such probiotics would bind appropriate carcinogens and prevent their invasion into the organism, thus inhibiting emergence of DNA-adducts and suppressing synthesis of specific autoantibodies that may promote carcinogenesis. The aim is to substantiate the concept of immuno-hormonal imbalance for the carcinogen-induced hormone-dependent tumors.

show abstract

Role of physiological factors in predicting the risk of oncological diseases on the basis of the polymorphism of the xenobiotic metabolism enzyme system

Cited by 2 publications

References 121 publications

Deciphering the Differential Toxic Responses of Radix aconiti lateralis praeparata in Healthy and Hydrocortisone-Pretreated Rats Based on Serum Metabolic Profiles

Deciphering the Differential Toxic Responses of Radix aconiti lateralis praeparata in Healthy and Hydrocortisone-Pretreated Rats Based on Serum Metabolic Profiles

Immune-hormonal imbalance in chemical cancerogenesis

Contact Info

Product

Resources

About