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1.
Metabolites ; 13(11)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37999231

RESUMO

A new approach for assisting in the diagnosis of coronary artery disease (CAD) as a cause of death is essential in cases where complete autopsy examinations are not feasible. The purine pathway has been associated with CAD patients, but the understanding of this pathway in postmortem changes needs to be explored. This study investigated the levels of blood purine metabolites in CAD after death. Heart blood samples (n = 60) were collected and divided into CAD (n = 23) and control groups (n = 37). Purine metabolites were measured via proton nuclear magnetic resonance. Guanosine triphosphate (GTP), nicotinamide adenine dinucleotide (NAD), and xanthine levels significantly decreased (p < 0.05); conversely, adenine and deoxyribose 5-phosphate levels significantly increased (p < 0.05) in the CAD group compared to the control group. Decreasing xanthine levels may serve as a marker for predicting the cause of death in CAD (AUC = 0.7). Our findings suggest that the purine pathway was interrupted by physiological processes after death, causing the metabolism of the deceased to differ from that of the living. Additionally, xanthine levels should be studied further to better understand their relationship with CAD and used as a biomarker for CAD diagnosis under decomposition and skeletonization settings.

2.
J Fungi (Basel) ; 9(8)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37623604

RESUMO

Environmental factors and climate are the primary factors influencing the microbial colonization and deterioration of cultural heritage in outdoor environments. Hence, it is imperative to investigate seasonal variations in microbial communities and the biodeterioration they cause. This study investigated the surfaces of sandstone sculptures at Wat Umong Suan Phutthatham, Chiang Mai, Thailand, during wet and dry seasons using culture-dependent and culture-independent approaches. The fungi isolated from the sandstone sculptures were assessed for biodeterioration attributes including drought tolerance, acid production, calcium crystal formation, and calcium precipitation. The results show that most of the fungal isolates exhibited significant potential for biodeterioration activities. Furthermore, a culture-independent approach was employed to investigate the fungal communities and assess their diversity, interrelationship, and predicted function. The fungal diversity and the communities varied seasonally. The functional prediction indicated that pathotroph-saprotroph fungi comprised the main fungal guild in the dry season, and pathotroph-saprotroph-symbiotroph fungi comprised the dominant guild in the wet season. Remarkably, a network analysis revealed numerous positive correlations among fungal taxa within each season, suggesting a potential synergy that promotes the biodeterioration of sandstone. These findings offer valuable insights into seasonal variations in fungal communities and their impacts on the biodeterioration of sandstone sculptures. This information can be utilized for monitoring, management, and maintenance strategies aimed at preserving this valuable cultural heritage.

3.
Foods ; 12(11)2023 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-37297420

RESUMO

Nelumbo nucifera Gaertn. (N. nucifera) tea is used as food and folk medicine to reduce toxicity in Southeast Asia. Mancozeb (Mz) is used for controlling fungi in agriculture and contains heavy metals. This study aimed to examine the effect of white N. nucifera petal tea on cognitive behavior, hippocampus histology, oxidative stress, and amino acid metabolism in rats poisoned with mancozeb. Seventy-two male Wistar rats were divided into nine groups (n = 8 in each). Y-maze spontaneous alternation test was used to assess cognitive behavior, and amino acid metabolism was investigated by nuclear magnetic resonance spectroscopy (1H-NMR) from blood. There was a significant increase in relative brain weight in the Mz co-administered with the highest dose (2.20 mg/kg bw) of white N. nucifera group. The levels of tryptophan, kynurenine, picolinic acid, and serotonin in blood showed a significant decrease in the Mz group and a significant increase in the Mz co-administered with low dose (0.55 mg/kg bw) of white N. nucifera group. However, there was no significant difference in cognitive behavior, hippocampus histology, oxidative stress, and corticosterone. This study demonstrated that a low dose of white N. nucifera petal tea has a neuroprotective effect against mancozeb.

4.
Toxics ; 11(6)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37368582

RESUMO

Mancozeb (Mz) is one of the most widely used pesticides that has been reported to cause adverse human health risks. White Nelumbo nucifera (N. nucifera) petals have therapeutic properties to prevent toxicity. Hence, this study attempted to determine the effects of N. nucifera extract on hepatotoxicity and oxidative stress in mancozeb-treated rats. Seventy-two male rats were divided into nine groups and designed with a control; N. nucifera extract was administered at the doses of 0.55, 1.1, and 2.2 mg/kg bw/day, Mz was administered at 500 mg/kg bw/day, and the co-treatment groups (N. nucifera and Mz) were administered 0.55, 1.1, and 2.2 mg/kg bw/day of N. nucifera followed by administering Mz 500 mg/kg bw/day daily for 30 days. The results showed that all doses of N. nucifera extract did not induce hepatic toxicity and could suppress the toxicity of mancozeb by increasing body weight gain and decreasing relative liver weight, lobular inflammation, and total injury score. The combination treatment also decreased the molecular markers of oxidative stress (2-hydroxybutyric acid, 4-hydroxynonenal, l-tyrosine, pentosidine, and N6-carboxymethyllysine). Furthermore, the reduced glutathione and oxidized glutathione contents were adjusted close to the normal level. Therefore, N. nucifera extract is a natural antioxidant supplement that could decrease the toxicity of mancozeb and can be safely consumed.

5.
Metabolites ; 12(12)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36557212

RESUMO

Methamphetamine (MA) level in urine has been used for judgment in MA consumption. Metabolism and intoxication of MA are correlated with the activity of cytochrome P450 2D6 (CYP2D6). The activity score (AS) is a potential tool for predicting exposure and personalized dose of drugs metabolized by CYP2D6. Prediction of the CYP2D6 activity score might be described as MA intoxication. The objective of this study was to categorize the CYP2D6 activity score using the urinary amphetamine (AM)/MA ratio. Urine samples (n = 23,258) were collected. The levels of MA and AM were determined by a gas chromatography-nitrogen-phosphorus detector. The log AS was calculated by an AM/MA ratio and classified into four groups following the percentile position: lower than the 2.5th, the 2.5th-the 50th, the 50th-97.5th, and greater than the 97.5th percentile, respectively. The AS value for males presented was less than 0.024, 0.024-0.141, 0.141-0.836, and greater than 0.836. Meanwhile, the AS values were revealed to be lower than 0.023, 0.023-0.148, 0.148-0.850, and higher than 0.850 for females. The AS value of CYP2D6 can be applied to describe the toxicity of MA in forensic crime scenes and relapse behavior.

6.
Life (Basel) ; 12(6)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35743884

RESUMO

This paper presents the first measurement of the investigation of the health impacts of indoor radon exposure and external dose from terrestrial radiation in Chiang Mai province during the dry season burning between 2018 and 2020. Indoor radon activity concentrations were carried out using a total of 220 RADUET detectors in 45 dwellings of Chiang Mai (7 districts) during burning and non-burning seasons. Results show that indoor radon activity concentration during the burning season (63 ± 33 Bq/m3) was significantly higher (p < 0.001) compared to the non-burning season (46 ± 19 Bq/m3), with an average annual value of 55 ± 28 Bq/m3. All values of indoor radon activity concentration were greater than the national (16 Bq/m3) and worldwide (39 Bq/m3) average values. In addition, the external dose from terrestrial radiation was measured using a car-borne survey during the burning season in 2018. The average absorbed rate in the air was 66 nGy/h, which is higher than the worldwide average value of 59 nGy/h. This might be due to the high activity concentrations of 238U and 323Th in the study area. With regards to the health risk assessment, the effective dose due to indoor radon exposure, external (outdoor) effective dose, and total annual effective dose were 1.6, 0.08, and 1.68 mSv/y, respectively. The total annual effective dose is higher than the worldwide average of 1.15 mSv/y. The excess lifetime cancer risk and radon-induced lung cancer risk during the burning season were 0.67% and 28.44 per million persons per year, respectively. Our results substantiate that indoor radon and natural radioactive elements in the air during the burning season are important contributors to the development of lung cancer.

7.
Plants (Basel) ; 11(5)2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35270108

RESUMO

The white Nelumbo nucifera petals aqueous extraction (NAE) was prominent in phytochemical content, antioxidant activity, and enhanced rat sperm viability induced by FeSO4, a heavy metal. Mancozeb (MZ) contains heavy metals and is widely used for fungal control in agriculture and industry. It induces oxidative stress and causes of spermatogenesis and reproductive organs' abnormalities in both humans and animals. The aims of the present study were to investigate the effects of white Nelumbo nucifera petals aqueous extraction (WNAE) on sperm quality in cattle sperm induced by MZ. Moreover, this study investigated phytochemical compounds by liquid chromatography-mass spectrometry. A protein profile related to sperm quality with SDS-page and sperm energy preservation for each treatment was determined. The results found nine phytochemical compounds, in which quercetin-3-O-arabinoglycoside was a major flavonoid that was found in the WNAE. MZ induced free radicals in cells, leading to LPO and protein oxidation, while decreasing sperm motility, sperm viability, acrosome integrity, and normal sperm morphology. The cattle sperm found four proteins related to sperm quality including MWs of 17, 31, 34, and 55 kDa. The WNAE effectively increased energy preservation, sperm motility, sperm viability, acrosome integrity, and normal sperm morphology. The WNAE enhanced sperm qualities by reducing oxidative stress. It might be suggested that WNAE has benefits for sperm preservation which may be used to guard against toxicity in animals or humans exposed to MZ contaminants.

8.
Biology (Basel) ; 11(2)2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35205094

RESUMO

Lanna painting is a unique type of painting in many temples in the Northern Thai region. Similar to most mural paintings, they usually decay over time partly due to the activity of microbes. This study aimed to investigate the microorganisms from two Lanna masterpiece paintings in two temples that differ in the numbers of visitors using both culture-dependent and -independent approaches. The microorganisms isolated from the murals were also tested for the biodeterioration activities including discoloration, acid production and calcium precipitation. Most microorganisms extracted from the paintings were able to discolor the paints, but only fungi were able to discolor, produce acids and precipitate calcium. The microorganism communities, diversity and functional prediction were also investigated using the culture-independent method. The diversity of microorganisms and functional prediction were different between the two temples. Gammaproteobacteria was the predominant group of bacteria in both temples. However, the fungal communities were different between the two temples as Aspergillus was the most abundant genus in the site with higher number of visitors [Buak Krok Luang temple (BK)]. Conversely, mural paintings at Tha Kham temple (TK) were dominated by the Neodevriesia genera. We noticed that a high number of visitors (Buak Krok Luang) was correlated with microbial contamination from humans while the microbial community at Tha Kham temple had a higher proportion of saprotrophs. These results could be applied to formulate a strategy to mitigate the amount of tourists as well as manage microorganism to slow down the biodeterioration process.

9.
Radiat Res ; 197(2): 122-130, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34634126

RESUMO

Radiation-induced bystander effect (RIBE) has been identified as an important contributing factor to tumor resistance and normal tissue damage. However, the RIBE in cancer and normal cells under hypoxia remain unclear. In this study, confluent A549 cancer and WI-38 normal cells were subjected to condition of hypoxia or normoxia, before exposure to high-LET protons microbeam. After 6 h incubation, cells were harvested and assayed for colony formation, micronucleus formation, chromosome aberration and western blotting. Our results show that there were differences of RIBE in bystander A549 and WI-38 cells under hypoxia and normoxia. The differences were also observed in the roles of HIF-1α expression in bystander A549 and WI-38 cells under both conditions. Furthermore, inhibition of gap junction intercellular communication (GJIC) showed a decrease in toxicity of hypoxia-treated bystander A549 cells, but increased in bystander WI-38 cells. These findings clearly support that GJIC protection of bystander normal cells from toxicity while enhancing in bystander cancer cells. Together, the data show a promising strategy for high-LET radiation in designing an entire new line of drugs, either increase or restore GJIC in bystander cancer cells which in turn leads to enhancement of radiation accuracy for treatment of hypoxic tumors.


Assuntos
Junções Comunicantes
10.
Life (Basel) ; 11(11)2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34833148

RESUMO

Radon is a major cause of lung cancer (LC) deaths among non-smokers worldwide. However, no serum biomarker for screening of LC risk in high residential radon (HRR) areas is available. Therefore, the aim of this study was to determine diagnostic values of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), human epididymis protein 4 (HE4), interleukin 8 (IL-8), migration inhibitory factor (MIF), tumor nuclear factor-alpha (TNF-α) and vascular endothelial growth factors (VEGF) occurring in high radon areas. Seventy-five LC non-smoker patients and seventy-five healthy controls (HC) were enrolled in this study. Among the HC groups, twenty-five HC were low residential radon (LRR) and fifty HC were HRR. Significantly higher (p < 0.0004) serum levels of CEA, Cyfra21-1, IL-8 and VEGF were found in the LC compared with the LRR and HRR groups. More importantly, significantly higher levels (p < 0.009) of serum CEA, Cyfra21-1 and IL-8 were observed in HRR compared with the LRR group. Likewise, a ROC curve demonstrated that serum CEA and Cyfra21-1 could better distinguish LC risk from HRR groups than IL-8. These results indicated that serum CEA and Cyfra21-1 were significantly increased in the HRR group and may be considered as potential biomarkers for individuals at high-risk to develop LC.

11.
Plants (Basel) ; 10(10)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34685828

RESUMO

Moringa oleifera Lam. (M. oleifera) has been called the "miracle tree" due to its attributes for therapy in various diseases. However, M. oleifera studies on the male reproductive system have been limited. The aim of this study was a phytochemical screening and investigation of the effects of M. oleifera leaf tea on sexual behavior, reproductive function and antioxidant activities. Male rats were fed with M. oleifera leaf tea extract at doses of 0.55, 1.10 and 2.20 mg/kg or distilled water for 30 days. The result showed that M. oleifera leaf tea contained rich total phenols and flavonoids. The courtship behavior, seminiferous tubule diameter, epithelium height, epithelium area, type A spermatogonia, and spermatogonia efficiency were significantly increased in all treatment groups. The groups treated with 1.10 and 2.20 mg/kg increased the number of Sertoli cells. The total of spermatogenic cells increased in the group treated with 0.55 mg/kg. M. oleifera leaf tea scavenged DPPH radical, ABTS radical and H2O2, and inhibited LPO and AGEs formation. Due to M. oleifera leaf tea containing rich total phenols, flavonoids, and antioxidants, it could enhance sexual function and the male reproductive system.

12.
Plants (Basel) ; 10(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34371577

RESUMO

Sacred lotus (Nelumbo nucifera Gaertn.; N. nucifera) is a common ingredient in traditional medicine and Thai recipes. Its petal is an agricultural waste from stamen production. There are limitations in the used and pharmacological data of the petals resulting in more petals waste. The aims of this study were to investigate the phytochemical contents, antioxidant activity, and potential effects on sperm viability of aqueous (NAE) and ethanolic extracts (NEE) of both red and white N. nucifera petals. The white NAE had the highest total phenolics content, total tannins content and maximal antioxidant activity. The white NEE had the highest concentration of total flavonoids. Quercetin was a major flavonoid and was found in the aqueous extracts. Both red and white of NAE in the range of 0.22 to 1.76 mg/mL increased sperm viability. The white NAE was prominent in phytochemical content, antioxidant activity, and both red and white NAE effectively increased rat sperm viability in the in vitro model. The white NAE enhanced sperm viability by decreasing oxidative stress. It might be suggested that the N. nucifera petals have benefits for sperm viability health promotion and may increase the economic value of agricultural waste.

13.
Toxins (Basel) ; 13(4)2021 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-33916734

RESUMO

Tetraponera rufonigra (Arboreal Bicoloured Ant) venom induces pain, inflammation, and anaphylaxis in people and has an increased incident in Southeast Asia regions. The bioactive components and mechanism of action of the ant venom are still limited. The aim of this research was to identify the protein composition and inflammatory process of the ant venom by using RAW 264.7 macrophage cells. The major venom proteins are composed of 5' nucleotidase, prolyl endopeptidase-like, aminopeptidase N, trypsin-3, venom protein, and phospholipase A2 (PLA2). The venom showed PLA2 activity and represented 0.46 µg of PLA2 bee venom equivalent/µg crude venom protein. The venom induced cytotoxic in a dose- and time-dependent manner with IC20 approximately at 4.01 µg/mL. The increased levels of COX-2 and PGE2 were observed after 1 h of treatment correlating with an upregulation of COX-2 expression. Moreover, the level of mPGES-1 expression was obviously increased after 12 h of venom induction. Hence, our results suggested that the induction of COX-2/mPGEs-1 pathway could be a direct pathway for the ant venom-induced inflammation.


Assuntos
Venenos de Formiga/toxicidade , Formigas , Mediadores da Inflamação/metabolismo , Inflamação/induzido quimicamente , Proteínas de Insetos/toxicidade , Macrófagos/efeitos dos fármacos , Animais , Venenos de Formiga/enzimologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Proteínas de Insetos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Prostaglandina-E Sintases/genética , Prostaglandina-E Sintases/metabolismo , Células RAW 264.7 , Fatores de Tempo , Regulação para Cima
14.
J Anal Toxicol ; 44(5): 470-481, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897465

RESUMO

We developed a robust analytical method for quantification of malondialdehyde (MDA) in urine and serum samples using dansylhydrazine (DH) as a derivatizing reagent. The derivatization procedure was partially carried out using an autosampler injection program to minimize errors associated with the low-volume addition of reagents and was optimized to yield a stable hydrazone derivative of MDA and its labeled d2-MDA analogue. The target MDA-DH derivatives were separated on an Agilent Zorbax Eclipse Plus Phenyl-Hexyl (3.0 × 100 mm, 3.5 µm) column. The mass-to-charge ratios of the target derivatives [(M+H)+ of 302 and 304 for MDA-DH and d2-MDA-DH, respectively] were analyzed in single ion monitoring mode using a single quadrupole mass spectrometer operated under positive electrospray ionization. The method limits of quantification were 5.63 nM (or 0.405 ng/mL) for urine analysis and 5.68 nM (or 0.409 ng/mL) for serum analysis. The quantification range for urine analysis was 5.63-500 nM (0.405-36.0 ng/mL) while the quantification range for serum analysis was 5.68-341 nM (0.409-24.6 ng/mL). The method showed good relative recoveries (98-103%), good accuracies (92-98%), and acceptable precisions (relative standard deviations 1.8-7.3% for inter-day precision; 1.8-6.1% for intra-day precision) as observed from the repeat analysis of quality control samples prepared at different concentrations. The method was used to measure MDA in individual urine samples (n = 287) and de-identified archived serum samples (n = 22) to assess the overall performance of the method. The results demonstrated that our method is capable of measuring urinary and serum levels of MDA, allowing its future application in epidemiologic investigations.


Assuntos
Compostos de Dansil/metabolismo , Hidrazinas/metabolismo , Malondialdeído/metabolismo , Líquidos Corporais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Hidrazinas/sangue , Hidrazinas/urina , Limite de Detecção , Malondialdeído/sangue , Malondialdeído/urina , Espectrometria de Massas em Tandem
15.
Metabolites ; 10(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861670

RESUMO

Coronary heart disease (CHD) is the major cause of death in sudden unexpected death (SUD) cases. Tryptophan (TRP) and its metabolites are correlated with the CHD patient but less studies in the SUD. The aim of this study was to evaluate the relationship of TRP and its metabolites with the CHD in the SUD cases. Blood samples and heart tissues were collected from CHD subjects (n = 31) and the control group (n = 72). Levels of kynurenine (KYN), kynurenic acid (KYA), xanthurenic acid (XAN), 3-hydroxyanthranillic acid (HAA), quinolinic acid (QA), picolinic acid (PA) and 5-hydroxyindoleacetic acid (HIAA) were determined by HPLC-DAD. A severity of heart occlusion was categorized into four groups, and the relationship was measured with the TRP metabolites. The HIAA and The KYN levels significantly differed (p < 0.01) between the CHD group and the control group. Lower levels of QA/XAN, PA/KA, HAA/XAN, KYN/XAN and KYN/TRP were found in the CHD group. However, PA/HAA, PA/HIAA, PA/KYN and XAN/KA values in the CHD group were higher than the control group (p < 0.05). This study revealed that the values of PA/KA and PA/HAA provided better choices for a CHD biomarker in postmortem bodies.

16.
Drug Metab Lett ; 10(3): 187-194, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27292117

RESUMO

OBJECTIVES: Caffeic acid (CAF) and its amide analogues, ethyl 1-(3',4'-dihydroxyphenyl) propen amide (EDPA), phenethyl 1-(3',4'-dihydroxyphenyl) propen amide (PEDPA), phenmethyl 1- (3',4'-dihydroxyphenyl) propen amide (PMDPA) and octyl 1-(3',4'-dihydroxyphenyl) propen amide (ODPA) were investigated for the inhibition of procarcinogen activating enzyme. METHODS: CYP1A2 and scavenging activity on formation of nitric oxide, superoxide anion, DPPH radical and hydroxyl radical. RESULTS: It was found that they inhibited CYP1A2 enzyme by uncompetitive inhibition. Apparent Ki values of CAF, EDPA, PEDPA, PMDPA and ODPA were 0.59, 0.39, 0.45, 0.75 and 0.80 µM, respectively suggesting potent inhibitors of CYP1A2. Moreover, they potentially scavenged nitric oxide radical with IC 50 values of 0.12, 0.22, 0.28, 0.22 and 0.51 mM, respectively. The IC50 values of superoxide anion scavenging were 0.20, 0.22, 0.44, 2.18 and 2.50 mM, respectively. 1, 1- diphenyl-2- picrylhydrazyl (DPPH) radical-scavenging ability, shown as IC50 values, were 0.41, 0.29, 0.30, 0.89 and 0.84 mM, respectively. Moreover, the hydroxyl radical scavenging in vitro model was shown as IC50 values of 23.22, 21.06, 17.10, 17.21 and 15.81 µM, respectively. CONCLUSION: From our results, caffeic acid and its amide analogues are in vitro inhibitors of human CYP1A2 catalytic activity and free radical formation. They may be useful to be developed as potential chemopreventive agents that block CYP1A2-mediated chemical carcinogenesis.


Assuntos
Ácidos Cafeicos/farmacologia , Inibidores do Citocromo P-450 CYP1A2/farmacologia , Citocromo P-450 CYP1A2/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Amidas/administração & dosagem , Amidas/química , Amidas/farmacologia , Ácidos Cafeicos/administração & dosagem , Ácidos Cafeicos/química , Citocromo P-450 CYP1A2/metabolismo , Inibidores do Citocromo P-450 CYP1A2/administração & dosagem , Inibidores do Citocromo P-450 CYP1A2/química , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/química , Radicais Livres/metabolismo , Humanos , Radical Hidroxila/metabolismo , Técnicas In Vitro , Concentração Inibidora 50 , Óxido Nítrico/metabolismo , Superóxidos/metabolismo
17.
Med Chem ; 7(2): 99-105, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21222608

RESUMO

Ethyl caffeate (EC), octyl caffeate(OC), benzyl caffeate(BC) and phenethyl caffeate(PC) were synthesized and evaluated for scavenging of superoxide anion, nitric oxide radical and 1,1-diphenyl-1-picrylhydrazyl radical (DPPH). Antioxidant activity was investigated with reducing power method. Pooled human liver microsome was used for investigating the effects on cytochrome P450 1A2 (CYP1A2) catalytic activities by using phenacetin as a substrate. Dixon and Cornish-Bowden plots were used for enzyme kinetic analysis. The EC, OC, BC and PC potentially inhibited superoxide anion, nitric oxide and DPPH radicals. IC(50) values of superoxide anion scavenging of EC, OC, BC and PC were 16.42, 79.83, 123.69 and 123.69 µg/ml, respectively. EC was more potent than OC and BC in terms of nitric oxide radical scavenger: IC(50) values of EC, OC and BC were 24.16, 37.34 and 52.64 µg/ml, respectively. In addition, the IC(50) values of EC, OC, BC and PC on DPPH radical scavenging were 70.00, 184.56, 285.34 and 866.54 µg/ ml, respectively. The IC(50) values of EC, OC, BC and PC on phenacetin O-deethylation were 124.98, 111.86, 156.68 and 31.05 µg/ml, respectively. Enzyme kinetics showed that the type of inhibition mechanism was mixed-type. The result of this study shows that caffeic acid ester analogues potentially scavenge free radicals and inhibit catalytic activity of CYP1A2. This may lead to important implications in the prevention of CYP1A2-mediated chemical carcinogenesis.


Assuntos
Ácidos Cafeicos/farmacologia , Inibidores do Citocromo P-450 CYP1A2 , Inibidores Enzimáticos/farmacologia , Ésteres/farmacologia , Radicais Livres/antagonistas & inibidores , Fígado/enzimologia , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Ácidos Cafeicos/química , Citocromo P-450 CYP1A2/metabolismo , Inibidores Enzimáticos/química , Ésteres/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Óxido Nítrico/metabolismo , Oxirredução/efeitos dos fármacos , Relação Estrutura-Atividade , Superóxidos/metabolismo
18.
Med Chem ; 5(6): 583-8, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20041835

RESUMO

Previous studies presented evidence that plants contain antioxidants that have free radical-scavenging properties. Overproduction of free radicals leads to oxidative stress, a factor associated with a variety of diseases, such as diabetes. Cytochrome P450 2E1 enzymes (CYP2E1) are involved in drug metabolism in the liver and metabolism of DNA-reaction generating intra-mitochondrial ROS, which leads to micro- and macro-vascular pathology in diabetes. Plant-based chemicals can affect CYP2E1 enzymes and related defense mechanisms, possibly leading to protection against oxidative stress. We investigated the effect of Solanum torvum (ST) extracts on the inhibition of CYP2E1 activity in human liver microsomes. ST extract was analyzed for antioxidant activity by the ABTS method. Polyphenolic compounds were measured by the total phenol content using the Folin-Ciocalteau reagent. Flavonoid and tannin content were analyzed by standard methods. Oxidative stress was evaluated by measuring lipid peroxidation by TBARS and superoxide anion scavenging levels in plasma from diabetic patients. Results showed that 10 mg/ml of ST had CYP2E1 catalytic inhibiting activity (57.16 %). The IC50 value of CYP2E1 catalytic inhibiting activity level was 5.14 mg/ml by concentration in a dependent manner. One gram of concentrated ST extract had an antioxidant activity index of 3.68 mg of trolox and 360.53 mg of ascorbic acid equivalent. Effects on free radical-scavenging, as measured by TBARS and superoxide anion, showed IC50 values of 20.60 and 10.26 microg/ml, respectively. Polyphenolic compounds found included phenol, flavonoid and tannin, measuring 160.30, 104.36 and 65.91 mg/g, respectively. These results imply that ST is a natural source of polyphenolic antioxidants, which have cytochrome P450 2E1 enzyme inhibiting and free radical scavenging properties, as related to lipid peroxidation and superoxide anion activity. ST could potentially be used for reducing oxidative stress in diabetes. Study for usage as a conventional medicine, including dosage and chronic toxicity in humans, should be pursued.


Assuntos
Inibidores do Citocromo P-450 CYP2E1 , Flavonoides/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Microssomos Hepáticos/efeitos dos fármacos , Fenóis/farmacologia , Solanum/química , Superóxidos/metabolismo , Adulto , Animais , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Flavonoides/uso terapêutico , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Microssomos Hepáticos/metabolismo , Fenóis/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Polifenóis
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