scholarly journals Effect of the leafy vegetable Solanum nigrum on the activities of some liver drug-metabolizing enzymes after aflatoxin B1 treatment in female rats

1991 ◽  
Vol 65 (1) ◽  
pp. 81-91 ◽  
Author(s):  
Paul F. Moundipa ◽  
Felicite Mbiapo Domngang
Keyword(s):  
Solanum Nigrum ◽  
Female Rats ◽  
Drug Metabolizing Enzymes ◽  
Uridine Diphosphate ◽  
Glutathione S Transferase ◽  
General Increase ◽  
Metabolizing Enzymes ◽  
Hepatic Microsomes ◽  
Demethylase Activity ◽  
Aflatoxin B

Wistar albino female rats were maintained for 10 d on diets containing various levels of the vegetable Solanum nigrum. Simultaneously, they received daily intraperitoneal injections of aflatoxin B1 (AFB1) (either 0.2 or 0.4 mg/kg body-weight) diluted in propylene glycol. At the end of the experiment, all animals were killed and their serum and hepatic microsomes were prepared for assay of enzymes. Results showed that aminopyrine N-demethylase activity increased 2.5-fold with 200 (S200) and 600 (S600) g S. nigrum/kg diets. Activity of uridine diphosphate glucuronyltransferase (UDPGT) (EC 2.4.17) also increased twofold. Similar results were obtained with glutathione S-transferase (EC 2.5.1.18) activity which increased by 60% with diet S600. After AFB1 treatment, a general increase in the activities of the above enzymes was found, except for UDPGT in the group fed on diet S600. When rats were fed on the diet without S. nigrum, AFB1 induced an increase in alkaline phosphatase (ALP) (EC 3. 1. 3. 1), aspartate aminotransferase (AST) (EC 2. 6. 1. 1) and γ-glutamyltransferase (γ-GT) (EC 2. 3. 2. 2) levels in the serum. AFB1 also induced increases in serum ALP and γ-GT levels when rats were fed on diet S600

scholarly journals The Modulation of Phase II Drug-Metabolizing Enzymes in Proliferating and Differentiated CaCo-2 Cells by Hop-Derived Prenylflavonoids

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2138 ◽  
Author(s):  
Kateřina Lněničková ◽  
Michaela Šadibolová ◽  
Petra Matoušková ◽  
Barbora Szotáková ◽  
Lenka Skálová ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Human Organism ◽  
Intestinal Cells ◽  
Drug Metabolizing Enzymes ◽  
Uridine Diphosphate ◽  
Glutathione S Transferase ◽  
Metabolizing Enzymes ◽  
Differentiated Cells ◽  
Colorectal Cancer Cells ◽  
Glucuronosyl Transferase

Prenylflavonoids in the human organism exhibit various health-beneficial activities, although they may interfere with drugs via the modulation of the expression and/or activity of drug-metabolizing enzymes. As intestinal cells are exposed to the highest concentrations of prenylflavonoids, we decided to study the cytotoxicity and modulatory effects of the four main hop-derived prenylflavonoids on the activities and mRNA expression of the main drug-conjugating enzymes in human CaCo-2 cells. Proliferating CaCo-2 cells were used for these purposes as a model of colorectal cancer cells, and differentiated CaCo-2 cells were used as an enterocyte-like model. All the tested prenylflavonoids inhibited the CaCo-2 cells proliferation, with xanthohumol proving the most effective (IC50 8.5 µM). The prenylflavonoids modulated the activities and expressions of the studied enzymes to a greater extent in the differentiated, as opposed to the proliferating, CaCo-2 cells. In the differentiated cells, all the prenylflavonoids caused a marked increase in glutathione S-transferase and catechol-O-methyltransferase activities, while the activity of sulfotransferase was significantly inhibited. Moreover, the prenylflavonoids upregulated the mRNA expression of uridine diphosphate (UDP)-glucuronosyl transferase 1A6 and downregulated that of glutathione S-transferase 1A1/2.

Effects of pregnenolone-16 α - carbonitrile on drug metabolizing enzymes in hypophysectomized female rats

Life Sciences ◽  
1987 ◽  
Vol 41 (9) ◽  
pp. 1141-1148 ◽  
Author(s):  
Marvin T. Williams ◽  
Denise Leonard ◽  
Lizette Simonet
Keyword(s):  
Female Rats ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes

Curcumin and resveratrol in combination modulate drug-metabolizing enzymes as well as antioxidant indices during lung carcinogenesis in mice

2015 ◽  
Vol 34 (6) ◽  
pp. 620-627 ◽  
Author(s):  
Y Liu ◽  
Y-M Wu ◽  
Y Yu ◽  
C-S Cao ◽  
J-H Zhang ◽  
...  
Keyword(s):  
Enzyme Activities ◽  
Cytochrome B5 ◽  
Combined Treatment ◽  
Drug Metabolizing Enzymes ◽  
Lung Carcinogenesis ◽  
Glutathione S Transferase ◽  
Metabolizing Enzymes ◽  
Aryl Hydrocarbon ◽  
Noticeable Improvement ◽  
Well Differentiated

This study investigated combined chemopreventive potential of curcumin and resveratrol during benzo(a)pyrene (BP)-induced lung carcinogenesis in mice. The mice were segregated into five groups that included normal control, BP-treated, BP + curcumin-treated, BP + resveratrol-treated, and BP + curcumin + resveratrol-treated groups. A statistically significant increase in the levels of lipid peroxidation (LPO) was observed in the lungs of mice after 22 weeks of single dose of benzo(a)pyrene. Further, BP treatment also resulted in a significant increase in the enzyme activities of aryl hydrocarbon hydroxylase as well as drug-metabolizing enzymes, namely cytocrome P450 and cytochrome b5. On the other hand, reduced glutathione (GSH) levels, the activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione- S-transferase (GST) were found to be significantly decreased following BP treatment. Supplementation with curcumin and resveratrol to BP-treated mice significantly decreased the LPO levels, GSH levels, and enzyme activities of drug-metabolizing enzymes. Further, treatment of curcumin and resveratrol to BP-treated mice significantly elevated the activities of SOD, GR, and GST. Histoarchitectural studies showed well-differentiated signs of lung carcinogenesis following BP administration to mice. However, combined treatment with curcumin and resveratrol resulted in a noticeable improvement in the lung histoarchitecture. This study, therefore, concludes that curcumin and resveratrol when supplemented in combination regulate drug-metabolizing enzymes as well as antioxidant enzymes during lung carcinogenesis in mice.

scholarly journals Investigation on Intestinal Proteins and Drug Metabolizing Enzymes in Simulated Microgravity Rats by a Proteomics Method

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4391
Author(s):  
Huayan Liu ◽  
Jingjing Guo ◽  
Yujuan Li ◽  
Yushi Zhang ◽  
Jiaping Wang ◽  
...  
Keyword(s):  
Intestinal Mucosa ◽  
Simulated Microgravity ◽  
Bioinformatic Analysis ◽  
Potential Effect ◽  
Drug Metabolizing Enzymes ◽  
Label Free ◽  
Glutathione S Transferase ◽  
Metabolizing Enzymes ◽  
Intestine Mucosa ◽  
Cyp2e1 Expression

The present study aimed to investigate the change of intestinal mucosa proteins, especially the alteration of intestinal drug metabolizing enzymes (IDMEs) following 14-day simulated microgravity. Morey–Holton tail-suspension analog was used to simulate microgravity. Intestinal mucosa proteins of rats were determined by label-free quantitative proteomic strategy. A total of 335 differentially expressed proteins (DEPs) were identified, 190 DEPs were upregulated, and 145 DEPs were downregulated. According to bioinformatic analysis, most of DEPs exhibited hydrolase, oxidoreductase, transferase, ligase, or lyase catalytic activity. DEPs were mainly enriched in metabolic pathways, including metabolism of amino acid, glucose, and carbon. Moreover, 11 of DEPs were involved in exogenous drug and xenobiotics metabolism. Owing to the importance of IDMEs for the efficacy and safety of oral drugs, the expression of cytochrome P450 1A2 (CYP1A2), CYP2D1, CYP3A2, CYP2E1, alcohol dehydrogenase 1 (ADH1), and glutathione S-transferase mu 5 (GSTM5) in rat intestine mucosa was determined by Western-blot. The activity of ADH, aldehyde dehydrogenase (ALDH) and GST was evaluated. Compared with control rats, the expression of CYP1A2, CYP2D1, CYP3A2, and ADH1 in the simulated microgravity (SMG) group of rats were dramatically decreased by 33.16%, 21.93%, 48.49%, and 22.83%, respectively. GSTM5 was significantly upregulated by 53.14% and CYP2E1 expression did not show a dramatical change in SMG group rats. Moreover, 14-day SMG reduced ADH activity, while ALDH and GST activities was not altered remarkably. It could be concluded that SMG dramatically affected the expression and activity of some IDMEs, which might alter the efficacy or safety of their substrate drugs under microgravity. The present study provided some preliminary information on IDMEs under microgravity. It revealed the potential effect of SMG on intestinal metabolism, which may be helpful to understand the intestinal health of astronauts and medication use.

Pharmacogenetics of common SNP affecting drug metabolizing enzymes: comparison of allele frequencies between European and Malaysian/Singaporean

2021 ◽  
Vol 36 (3) ◽  
pp. 173-181
Author(s):  
Nur Salwani Bakar
Keyword(s):  
Ethnic Diversity ◽  
Drug Response ◽  
Association Studies ◽  
Allele Frequencies ◽  
Drug Metabolizing Enzymes ◽  
Uridine Diphosphate ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Asian Populations ◽  
Two Populations

Abstract Compared to Europe, data on genetic variation in genes transcribing drug metabolizing enzymes among Asian is limited due to ethnic diversity. Here we compare frequencies for clinically relevant single nucleotide polymorphism (SNP) commonly observed in drug metabolizing enzymes between European and Malaysian/Singaporean. Minor allele frequencies (MAF) for the indicated SNPs for European, South Asian and East Asian populations were obtained from the NCBI website (https://www.ncbi.nlm.nih.gov/snp). The SNP prevalence among Malaysian/Singaporean was characterized from gene association studies. Generally, some SNPs in CYP2D6 and CYP2C19 do not show good agreement between the two populations as to the MAF value obtained. CYP2D6*4 tends to be more common among European, whereas CYP2D6*10 is more common in Malays and Chinese among Singaporean. Regardless of different phenotype, MAF of CYP2D6*4 for Indians is similar to that seen by the European. Singaporeans show smaller MAF for CYP2C19*17 but higher CYP2C19*2 frequencies as opposed to European ones. Following growing attention to the contribution of CYP3A4/5, N-acetyltransferases (NAT2), thiopurine methyltransferase (TPMT) and uridine diphosphate glucuronosyltransferases (UGT)2B7 in predicting drug response across Europe, there are limited pharmacogenetics (PGx) studies examining the gene-drug interaction among Malaysian/Singaporean. To better understand the heterogeneity of the drug response, PGx studies for the abovementioned enzymes between ethnics in Malaysian/Singaporean should be identified.

scholarly journals Effects of Curcumin Analogue, 2, 6-Bis (2, 5-Dimethoxybenzylidene) Cyclohexanone (BDMC33) on the Activities of Drug-Metabolizing Enzymes in Cultured Caco-2 Cell Model

2016 ◽  
Vol 8 (01) ◽  
Author(s):  
Ndatsu Yakubu ◽  
Syahida Ahmad ◽  
Faridah Abas ◽  
Umaru Mohammed
Keyword(s):  
Aldol Condensation ◽  
Cell Model ◽  
Drug Metabolizing Enzymes ◽  
Cytochrome P450 Reductase ◽  
Systemic Delivery ◽  
Glutathione S Transferase ◽  
Curcumin Analog ◽  
Metabolizing Enzymes ◽  
Curcumin Analogues ◽  
Anti Inflammatory

Poor systemic delivery of curcumin outside the gut due to its rapid metabolism has severely limited its application to many chronic diseases. Previously, our research group synthesized curcumin analogues 2, 6-bis (2, 5-dimethoxybenzylidene) cyclohexanone (BDMC33) that has potent anti-inflammatory activities. Therefore, the aim of this study is to evaluate the effects of curcumin analog (BDMC33) on the activities of drug metabolizing enzymes in Caco-2 cells, which was compared with that of curcumin and 3-(2-Fluorobenzylidene)-5-(2-fluorocyclohexylmethylene)-piperidin-4-one (EF-24). BDMC-33 was synthesized through the appropriate reaction of the aromatic aldehyde with cyclohexanone, under base catalyzed aldol condensation, at the ratio of ketone: aldehyde (1:2). Activity of drug metabolizing enzymes such as NADPH-cytochrome p450 reductase (CPR), UDP-glucuronosyltransferase (UGT), glutathione-S-transferase (GST) and Sulfotransferase (SULT) in Caco-2 cells were evaluated upon exposure to 50µM of BDMC33, curcumin, and EF-24, separately, for 4 hours. The BDMC33, EF-24, and curcumin treatments did not affect the activities of UGT, GST, SULT, and CPR in respect to their controls (29.45, 27.18, 23.64 and 2.08µmol/mg), respectively, at all periods of incubation. Hence, BDMC33 was able to maintain the activities of both phases I and II drug metabolizing enzymes, and therefore it could be a potential lead, anti-inflammatory agents.

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