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1.
The present study was undertaken to investigate the hepatoprotective effect of Boschniakia rossica extract (BRE), rich in phenylpropanoid glycoside and iridoid glucoside, on CCl4-induced liver damage. Male Wistar rats were randomly divided into six groups of ten each. While the first group was maintained as normal control, groups II–VI were administered 0.5 ml/kg CCl4 (model), 100 mg/kg BRE plus CCl4, 200 mg/kg BRE plus CCl4, 50 mg/kg silymarin plus CCl4 and 200 mg/kg BRE, respectively. CCl4 challenge not only elevated the serum marker enzyme activities and reduced albumin (ALB) level but also increased liver oxidative stress, as evidenced by elevated lipid hydroperoxide (LOOH) and malondialdehyde (MDA) concentrations, combined with suppressed potential of hepatic antioxidative defense system including superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content. Furthermore, serum tumor necrosis factor-α (TNF-α), hepatic nitrite level, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein contents were elevated while cytochrome P450 2E1 (CYP2E1) expression and function were inhibited. Preadministration of BRE not only reversed the significant changes in serum toxicity markers, hepatic oxidative stress, xenobiotic metabolizing enzymes and proinflammatory mediators induced by CCl4 but also restored liver CYP2E1 level and function. Interestingly, the protein expression of heme oxygenase-1 (HO-1) was further elevated by BRE treatment, which was markedly increased after CCl4 challenge. These results demonstrate that BRE exhibits protective effect on CCl4-induced acute hepatic injury via, at least in part, reduced oxidative stress, suppressed inflammatory responses and induced HO-1 protein expression combined with improved CYP2E1 level and function in liver. 相似文献
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Recai Tunca Mahmut Sozmen Mehmet Citil Mahmut Karapehlivan Serpil Erginsoy Kursad Yapar 《Experimental and toxicologic pathology》2009,61(3):243-255
An in vivo assessment for the protective effects of silymarin for pyridine toxicity was investigated through cytochrome P450 isoform CYP1A1 and inducible nitric oxide synthase (iNOS) activity prevention. Moreover, the effect of pyridine-induced oxidative stress on metallothionein I-II (MT), a scavenger of oxygen-derived free radicals, was investigated. Forty Syrian hamsters were allocated into 4 groups. Syrian hamsters were dosed with pyridine (400 mg/kg) intraperitoneally with and without silymarin (200 mg/kg daily by gavage) for 4 days. Pyridine induced diffuse degeneration and necrosis of the proximal and distal renal tubular cells; cloudy swelling, necrosis and hepatocellular atypia of the liver; and degenerative changes in the myocardium. The degree of pathological alterations was less severe with simultaneous silymarin application. CYP1A1, iNOS and MT expression levels were elevated in liver, kidney and heart in response to acute pyridine toxicity. Silymarin application abolished or significantly suppressed the induction of CYP1A1, iNOS and MT expressions in liver, kidney and heart of the pyridine-treated Syrian hamsters. Enhanced synthesis of MT by pyridine possibly implies a purposive cellular response to prevent damage caused by oxygen radicals. However, silymarin significantly reduced the oxidative-stress-inducing effect of pyridine as reflected by decreased synthesis of MT. These results suggest that through oxidant generation, pyridine may cause alteration of the metabolic ways, including nitric oxide-mediated CYP1A1 activity. 相似文献
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Li-Hua Pan Jun Lu Jian-Ping Luo Xue-Qiang Zha Jun-Hui Wang 《Experimental and toxicologic pathology》2012,64(7-8):899-904
This study was carried out to investigate the preventive effects of galactoglucomannan (GGM), a homogeneous polysaccharide from Dendrobium huoshanense, on liver injury and fibrosis induced by sodium selenite. Sprague–Dawley rats injected subcutaneously with sodium selenite at the dosage of 3.28 mg kg?1 b. wt. were set as the model groups. Rats treated with sodium selenite at the dosage of 3.28 mg kg?1 b. wt. and GGM at 50–200 mg kg?1 b. wt. were set as the prevention groups. Biochemical and histological analysis showed that GGM significantly ameliorated selenite-induced liver injury and fibrosis in rats. Oral administration of GGM effectively attenuated the toxicity of selenite to liver tissue, which was judged both by the decreased activities of serum hepatic enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and by liver histopathological examination. Meanwhile, GGM also reduced the levels of H2O2 and malondialdehyde (MDA), elevated the levels of GSH, restored the fluidity of hepatic plasma membrane, and retained the activities of endogenous enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). The prevention of selenite-induced liver injury and fibrosis by GGM was further supported by the reduced expression of transforming growth factor-β1 (TGF-β1) and type I collagen. These results suggested that GGM may be developed into a novel antifibrotic agent for the prevention of liver injury and fibrosis. 相似文献
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BackgroundResidual phenylalanine hydroxylase (PAH) activity is the key determinant for the phenotype severity in phenylketonuria (PKU) patients and correlates with the patient's genotype. Activity of in vitro expressed mutant PAH may predict the patient's phenotype and response to tetrahydrobiopterin (BH4), the cofactor of PAH.MethodsA robust LC–ESI-MSMS PAH assay for the quantification of phenylalanine and tyrosine was developed. We measured PAH activity a) of the PAH mutations p.Y417C, p.I65T, p.R261Q, p.E280A, p.R158Q, p.R408W, and p.E390G expressed in eukaryotic COS-1 cells; b) in different cell lines (e.g. Huh-7, Hep3B); and c) in liver, brain, and kidney tissue from wild-type and PKU mice.ResultsThe PAH assay was linear for phenylalanine and tyrosine (r2 ≥ 0.99), with a detection limit of 105 nmol/L for Phe and 398 nmol/L for Tyr. Intra-assay and inter-assay coefficients of variation were < 5.3% and < 6.2%, respectively, for the p.R158Q variant in lower tyrosine range. Recovery of tyrosine was 100%. Compared to the wild-type enzyme, the highest PAH activity at standard conditions (1 mmol/L L-Phe; 200 μmol/L BH4) was found for the mutant p.Y417C (76%), followed by p.E390G (54%), p.R261Q (43%), p.I65T (33%), p.E280A (15%), p.R158Q (5%), and p.R408W (2%). A relative high PAH activity was found in kidney (33% of the liver activity), but none in brain.ConclusionsThis novel method is highly sensitive, specific, reproducible, and efficient, allowing the quantification of PAH activity in different cells or tissue extracts using minimum amounts of samples under standardized conditions. 相似文献
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Trivendra Tripathi Aijaz Ahmed Khan Mohammad Shahid Haris M. Khan Mashiatullah Siddiqui Rahat Ali Khan Abbas Ali Mahdi Abida Malik 《Experimental and toxicologic pathology》2013,65(3):271-275
The present study was designed to investigate the biochemical and histopathological changes in the livers of rabbits treated with histamine and histamine receptors (H1R–H4R)-agonist. The cohort comprised of six groups containing five rabbits each. Control group received sterile distilled water (1 mL/kg × b.i.d.) and treated groups received subcutaneous histamine (100 μg/kg × b.i.d.) and H1R–H4R-agonist (histamine trifluoro-methyl toluidide, amthamine, R-[?]-α-methylhistamine, clobenpropit, respectively) each in a dose of 10 μg/kg × b.i.d. (12 h [8 am and 8 pm]) for 30 days. Hepatotoxicity due to these agonists was analyzed using biochemical and histopathological methods. Histamine and H1R–H3R-agonist were found to be hepatotoxic as shown by statistically significant (p < 0.05) elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), most marked in the H3R-agonist group. However, their levels in H4R-agonist group remained very similar to the control group. The entire drug treated groups as compared to control showed significant elevated levels of alkaline phosphatase (ALP). Histopathological examination revealed obvious changes in histamine, H2R- and H3R-agonist groups in terms of alteration of hepatic microstructure, congestion, focal necrosis and increased incidence of multinucleate hepatocytes while H1R and H4R groups showed minimal changes. From the findings of the present study it may be concluded that on repeated administration, histamine and HR-agonists-induced hepatotoxicity which is most pronounced with H3R-agonist though not severe enough to jeopardize the vital functions of liver and warrants further long-term studies. 相似文献
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Karthikkumar Venkatachalam Sivagami Gunasekaran Victor Antony Santiago Jesudoss Nalini Namasivayam 《Experimental and toxicologic pathology》2013,65(4):409-418
This study was carried out to investigate the chemopreventive potential of rosmarinic acid (RA) against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the effect of RA on tumour formation, antioxidant enzymes, cytochrome P450 content, p-nitrophenol hydroxylase and GST activities. Rats were divided into six groups and fed modified pellet diet for the entire experimental period. Group 1 served as control, group 2 received RA (10 mg/kg b.w.). Groups 3–6 were induced colon cancer by injecting DMH (20 mg/kg b.w.) subcutaneously once a week for the first four weeks (groups 3–6). In addition, RA was administered at the doses of 2.5, 5 and 10 mg/kg b.w. to groups 4–6 respectively. DMH treated rats showed large number of colonic tumours; decreased lipid peroxidation; decreased antioxidant status; elevated CYP450 content and PNPH activities; and decreased GST activity in the liver and colon. Supplementation with RA (5 mg kg/b.w.) to DMH treated rats significantly decreased the number of polyps (50%); reversed the markers of oxidative stress (21.0%); antioxidant status (38.55%); CYP450 content (29.41%); and PNPH activities (21.9%). RA at the dose of 5 mg/kg b.w. showed a most pronounced effect and could be used as a possible chemopreventive agent against colon cancer. 相似文献
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Maedeh Arabian Nahid Aboutaleb Mansoureh Soleimani Marjan Ajami Rouhollah Habibey Hamidreza Pazoki-Toroudi 《Advances in medical sciences》2018,63(2):213-219
Purpose
Pharmacologic preconditioning, through activating several mechanisms and mediators, can increase the tolerance of different tissues against ischemia/reperfusion (I/R) injury. Recent studies have shown that morphine preconditioning has protective effects in different organs, especially in the heart. Nevertheless, its mechanisms are not well elucidated in the brain. The present study aimed to clarify whether the activation of mitochondrial KATP (mKATP) channels in chronic morphine (CM) preconditioning could decrease hippocampus damage following I/R injury.Materials and methods
CM preconditioning was performed by the administration of additive doses of morphine for 5 days before I/R injury induction. I/R injury was induced by the occlusion of bilateral common carotid arteries. The possible role of mKATP channels was evaluated by the injection of 5-hydroxydecanoate (5-HD) before I/R injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was performed to detect apoptosis in hippocampal neurons. The expressions of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (BAX) and levels of malondialdehyde (MDA) and catalase (CAT) enzymes were assessed.Results
CM attenuated apoptosis in the hippocampal CA1 neurons (P < 0.001 vs I/R), and mKATP channel blocking with 5-HD significantly increased apoptosis (P < 0.001 vs CM + I/R). CM increased CAT activity (P < 0.05 vs I/R) and Bcl-2 protein expression (P < 0.01 vs I/R), while it decreased MDA level (P < 0.05 vs I/R) and BAX protein expression (P < 0.05 vs I/R). Pretreatment with 5-HD abolished all the above-mentioned effects of CM.Conclusions
These findings describe novel evidence whereby CM preconditioning in hippocampal CA1 neurons can improve oxidative stress and apoptosis through the activation of mKATP channels and eventually protect the hippocampal tissue against I/R injury. 相似文献9.
Argininic acid alters markers of cellular oxidative damage in vitro: Protective role of antioxidants
Daniela Delwing-de Lima Simone Sasso Leticia Dalmedico Débora Delwing-Dal Magro Eduardo Manoel Pereira Angela T.S. Wyse 《Experimental and toxicologic pathology》2017,69(8):605-611
We, herein, investigated the in vitro effects of argininic acid on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the blood, kidney and liver of 60-day-old rats. We also verified the influence of the antioxidants (each at 1.0 mM) trolox and ascorbic acid, as well as of NG-nitro-l-arginine methyl ester (L-NAME) at 1.0 mM, a nitric oxide synthase inhibitor, on the effects elicited by argininic acid on the parameters tested. The liver, renal cortex and renal medulla were homogenized in 10 vol (1:10w/v) of 20 mM sodium phosphate buffer, pH 7.4, containing 140 mM KCl; and erythrocytes and plasma were prepared from whole blood samples obtained from rats. For in vitro experiments, the samples were pre-incubated for 1 h at 37 °C in the presence of argininic acid at final concentrations of 0.1, 1.0 and 5.0 μM. Control experiments were performed without the addition of argininic acid. Results showed that argininic acid (5.0 μM) enhanced CAT and SOD activities and decreased GSH-Px activity in the erythrocytes, increased CAT and decreased GSH-Px activities in the renal cortex and decreased CAT and SOD activities in the renal medulla of 60-day-old rats, as compared to the control group. Antioxidants and/or L-NAME prevented most of the alterations caused by argininic acid on the oxidative stress parameters evaluated. Data suggest that argininic acid alters antioxidant defenses in the blood and kidney of rats; however, in the presence of antioxidants and L-NAME, most of these alterations in oxidative stress were prevented. These findings suggest that oxidative stress may be make an important contribution to the damage caused by argininic acid in hyperargininemic patients and that treatment with antioxidants may be beneficial in this pathology. 相似文献
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《Transfusion Clinique et Biologique》2022,29(2):153-160
ObjectivesWe aimed to determine a threshold cutoff for hepcidin, ferritin, and the hepcidin-to-ferritin ratio in the diagnosis of liver fibrosis caused by iron overload in chronic hepatitis C virus (HCV)-free ß-thalassemia major patients .MethodsThis 1:1-matched case-control study included 102 individuals (3–30 yr.); 51 ß-thalassemia major patients with iron overload , and 51 apparently healthy individuals.ResultsThe highest areas under the receiver operating characteristic curves (AUC-ROCs) for the diagnosis of patients vs. controls had overlapping 95% confidence intervals (CIs): serum hepcidin (0.758; 0.64–0.87; P ? 0.001), serum ferritin (1.000; 1.00–1.00; P ?0.001), and the hepcidin/ferritin ratio (1.000; 1.00–1.00; P ? 0.001). For differentiation of patients with liver fibrosis stages of F0–F1 vs. F2–F4 and F0–F1 vs. F3–F4, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with P-values ? 0.001 were the only statistically significant parameters, while the AUC-ROCs of the hepcidin/ferritin ratio (0.631, P = 0.188 and 0.684, P = 0.098) exhibited 90% and 89.5% sensitivity, respectively, in staging liver fibrosis.ConclusionOur results showed that the hepcidin/ferritin ratio is as effective as the APRI and maybe a better predictor for the diagnosis of liver fibrosis and discriminating its stages, with excellent sensitivity and specificity compared to its components. 相似文献
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Mongi Saoudi Mohamed Salah Allagui Abdelwaheb Abdelmouleh Kamel Jamoussi Abdelfattah El Feki 《Experimental and toxicologic pathology》2010,62(6):601-605
The aerial parts of Artemisia campestris are often used in Tunisian poisoning cases and are known to possess significant antioxidant activities. The objective of this study is to evaluate the protective effects of an aqueous extract (5 g/l) of A. campestris leaves and stems (AE), on oxidative damages induced by liver extract (LT) from poisonous fish Lagocephalus lagocephalus in wistar rats. AE was found to contain large amounts of K+, Na+, Ca++ and significant antioxidant capacities highlighted by high level of polyphenols and scavenging activities for DPPH and superoxide anion.LT-injected rats (1 ml/100 g body wt) for 10 days showed (1) a reduced appetite and diarrhea resulting in a lower growth rate than controls, (2) a decrease in serum ALT and AST activities suggesting liver functional disorders, (3) an increase of serum urea and creatinine and reduced serum sodium and potassium concentrations highlighting renal insufficiency and (4) an oxidative stress as evidenced by the raise of TBARS and the inhibition of SOD, CAT and GSH-Px activities in liver, kidney and brain tissuesAbsorption of AE as a drink, for 20 days (10 pre-treatment days+10 experiment days) did not lead significant change of studied parameters but prevented all the disorders induced by LT. 相似文献
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Trivendra Tripathi Mohammad Shahid Adil Raza Haris M. Khan Rahat Ali Khan Abbas Ali Mahdi Mashiatullah Siddiqui Abida Malik Aijaz Ahmed Khan 《Experimental and toxicologic pathology》2012,64(7-8):875-881
ObjectiveThe present study was designed to delineate the hepatotoxicological roles of histamine dose-dependently in immunized rabbits.MethodsThe cohort comprised of three groups (II, III and IV), containing 18 rabbits each, and received subcutaneous histamine 50 μg/kg, 100 μg/kg and 200 μg/kg, respectively for 10 days (b.i.d., starting from 3 days prior to immunization until 7 days after immunization). Group I (control, n = 18) received subcutaneous sterile distilled water for 10 days. They were subsequently immunized at day 3 with intravenous injection of SRBC (1 × 109 cells/ml). Blood samples were collected on pre-immunization (pre-I) day 0, as well as on days 7-, 14-, 21-, 28- and 58-post-immunization (post-I). Biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin [total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB)] were determined.ResultsGroups II and IV revealed a significant decrease (on day 0-pre-I) and a significant increase (on days 7-, 14-, 21-, 28- and 58-post-I) in ALT and AST levels, when compared with the corresponding values of groups I and III while group II showed a significant increase in ALT and AST levels as compared to group IV. ALP levels in groups II, III and IV showed a significant enhancement when compared with group I. Moreover, results of TB, DB and IB demonstrated increased levels in group III when compared with groups I, II and IV. The results were found statistically significant (p < 0.05).ConclusionShort-term treatment of histamine produces dose-dependent differential patterns of hepatic dysfunctions suggestive mild liver degeneration warranting further long-term studies. 相似文献
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《Experimental and toxicologic pathology》2014,66(7):281-291
The beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) has been explored against hyperglycemia associated secondary complications in streptozotocin induced diabetic rat model. The experimental groups consist of normal control (NC), diabetic control (DC), DC + metformin 100 mg kg−1 bwd, DC + SCE 250 and DC + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers like malondialdehyde, protein carbonyls compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited 46.28% of glucose lowering effect and decreased HOMA-IR (2.47), % HbA1c (6.61), lens AR activity (15.99%), and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug. 相似文献
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Oyagbemi Ademola Adetokunbo Azeez Odunayo Ibraheem Iji Oluwafikemi Temitayo 《Experimental and toxicologic pathology》2012,64(7-8):883-887
This study was designed to investigate the effect of prolonged oral exposure of cockerels to disinfectant (Iodosteryl®) present in drinking water and its ability to induce liver damage and oxidative stress. Thirty-two healthy birds were used for this study. They were grouped into four groups of eight per group. Group I received 10 ml/kg body weight of physiological saline. Groups II, III and IV received 1 part per million, 2 part per million and 4 part per million of Iodosteryl® in their drinking water for six weeks. The results revealed significant (P < 0.05) increase in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities in a dose-dependent manner in birds administered with Iodosteryl® when compared with control. Significant (P < 0.05) increase in sodium and potassium ions was obtained from birds that received Iodosteryl® (4 part per million) compared with control. Also, there was significant (P < 0.05) increase in total cholesterol, triglycerides, high density lipoprotein and low density lipoprotein levels in all treatment groups (1, 2 and 4 part per million) compared with control. Serum blood urea nitrogen levels increased significantly (P < 0.05) in a dose-dependent manner. Biologic markers of oxidative stress (malondialdehyde and hydrogen peroxide generation) increased significantly with concomitant significant (P < 0.05) decrease in serum glutathione level in a dose-dependent manner when compared with control. Histological sections revealed hepatic congestion, vacuolation and fibrosis at varying concentration of Iodosteryl®. Overall, Iodosteryl® induced hepatic damage, increased oxidative stress and decreased antioxidant defense system; hence exposure of both animals and humans to prolonged iodine disinfectant is potentially harmful. 相似文献
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Hisako Fujimura Naoko Murakami Satoko Miwa Chinami Aruga Wataru Toriumi 《Experimental and toxicologic pathology》2012,64(5):527-533
To investigate the suitability of H4IIE cells for detecting cytochrome P450 (CYP) induction in vitro, we compared CYP induction by typical CYP inducers in H4IIE cells and rat primary hepatocytes by examining gene expression and enzyme activity, and by immunocytochemistry. The cells were preincubated with 0.1 μM of dexamethasone (DEX) for 24 h, followed by 48 h of exposure to 10 μM of beta-naphthoflavone (bNF), 100 μM of phenobarbital (PB) and 10 μM of DEX. Cyp1a1, Cyp2b1/2 and Cyp3a23/3a1 (Cyp3a23) expressions in H4IIE cells were up-regulated 280-, 1.5- and 65-fold relative to those in vehicle-treated cells, respectively. The fold inductions of those expressions in rat primary hepatocytes were 80-, 33- and 152-fold, respectively. Comprehensive gene expression analysis using DNA microarrays showed that Cyp3a23, Gsta2, Ugt2b12, Udpgt and Sult2a1 expressions were up-regulated in H4IIE cells exposed to 10 μM of DEX. CYP3A activity was not increased, but some H4IIE cells exposed to DEX were stained strongly with anti-CYP3A antibody. We cloned these cells and obtained cloned H4IIE (cH4IIE) cells with expression level of Cyp3a23 higher than those of vehicle-treated cells. It was confirmed that preincubation with 0.1 μM of DEX increased pregnane X receptor (Pxr) expression level and enhanced the Cyp3a23 induction effects of test compounds significantly. Retrospective examination of in vitro CYP induction assay using cH4IIE cells resulted in 80% correlation with the data from in vivo rat toxicity studies. These results suggested that cH4IIE cells are suitable for evaluating the potentials of a compound to induce CYP3A23 expression. 相似文献
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Hashemi M Bahari A Hashemzehi N Moazeni-Roodi A Shafieipour S Bakhshipour A Ghavami S 《Pathophysiology》2012,19(2):115-119
BackgroundThe aim of the study was to investigate paraoxonase-1 (PON1) and aryl esterase (ARE) activities in patients with nonalcoholic fatty liver disease (NAFLD).Materials and methodsThis case–control study was done on 83 subjects with confirmed NAFLD (50 male, 33 female, age; 40.46 ± 12.13 years) and 138 healthy individuals (75 male, 63 female; age; 40.94 ± 14.50 years). PON1, salt-stimulated PON1 and ARE activities were determined using paraoxon and phenyl acetate as substrate, respectively.ResultsThe levels of PON1 activities in NAFLD and healthy individuals were 90.83 ± 63.65 IU/L and 79.41 ± 68.14 IU/L, respectively. There was no significant differences regarding PON1 activity between NAFLD and healthy subjects (p = 0.229). While, ARE activity was significantly higher in NAFLD (83.34 ± 28.36 KU/L) than in normal subjects (64.06 ± 27.49 KU/L) (p < 0.001).ConclusionsOur results showed that PON1 activity is not a promising biomarker for the evaluation of NAFLD while arylesterase may have, but further studies in larger samples with different ethnic groups are required to validate our findings. 相似文献
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《Genetics in medicine》2020,22(7):1247-1253
PurposeLittle is known about how many insured patients receive pharmacogenetic testing. We describe trends of single-gene pharmacogenetic testing in a US managed care population, and demographic and clinical characteristics of patients who received a test.MethodsWe leveraged a random sample of nearly 11 million patients from a data set of paid medical and pharmacy claims to identify patients with at least one claim indicating receipt of at least one of these single-gene pharmacogenetic tests: CYP2C19, CYP2D6, CYP2C9, VKORC1, UGT1A1, and HLA class 1 typing.ResultsFrom 1 January 2013 to 30 September 2017, 5712 patients received at least one pharmacogenetic test (55% female; mean age = 43 years). The median number of tests per patient was 3 (mean = 2.7, max = 12); 54% were processed through Managed Medicare/Medicaid, while 45% were processed through commercial insurance. The total number of pharmacogenetic tests received more than doubled from 2013 (n = 1955) to 2015 (n = 4192), then decreased slightly in 2016 (n = 3946). The most common test was CYP2C19 (n = 4719), and “long-term (current) use of other medications” was the most common diagnosis.ConclusionPharmacogenetic testing through patients’ insurance was low, but more than doubled from 2013 to 2016. This study highlights the need to better understand utilization patterns and insurance coverage for pharmacogenetic tests. 相似文献
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Ganiyu Oboh Toyin L. Akomolafe Stephen A. Adefegha Abayomi O. Adetuyi 《Experimental and toxicologic pathology》2012,64(6):591-596
Cyclophosphamide is an anticancer and immunosuppressant drug that induces reactive oxygen species (ROS) production, so causing malondialdehyde (MDA) production, which is toxic to cells. This study therefore sought to assess the antioxidant and the protective effect of dietary inclusion (0.5 and 1.0%) of yellow dye from root of Brimstone tree (used to enhance the sensory quality of foods and in folk medicine) on cyclophosphamide-induced oxidative stress in brain. Wistar strain albino rats were placed on diet containing 0.5 and 1.0% yellow dye preparation from root of Brimstone tree for 14 days. Intraperitoneal administration of cyclophosphamide (75 mg/kg of body weight) 24 h before the termination of the experiment caused a significant (P < 0.05) increase in the brain malondialdehyde (MDA) content (147.2%) and serum activities of aspartate aminotransferase (AST) (21.7 UI/l), alanine amino-transferase (ALT) (29.6 UI/l), alkaline phosphatase (43.8UI/l) and total bilirubin (1.7 mg/dl). However, there was a significant decrease (P < 0.05) in the MDA of content of the brain and serum enzyme activities, in those rats fed diet containing the yellow dye in a dose dependent manner. The inhibition of oxidative stress in brain and serum enzymes and metabolites by the dye could be attributed to its high total phenol content and antioxidant activity as typified by its reducing power, free-radical scavenging ability, Fe(II) chelating ability and inhibition of lipid peroxidation. Therefore, dietary inclusion of the yellow dye from root of Brimstone tree could prevent cyclophosphamide-induced oxidative stress in brain and the associated toxicity to the liver. 相似文献
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Mohd Salim Reshi Sadhana Shrivastava Amita Jaswal Neelu Sinha Chhavi Uthra Sangeeta Shukla 《Experimental and toxicologic pathology》2017,69(4):231-240
Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2 g/kg p.o. once only. After 24 h of APAP intoxication, animals were treated with three different doses of AuNPs (50 μg/kg, 100 μg/kg, 150 μg/kg) orally or silymarin at a dose of 50 mg/kg p.o., once only. Animals of all the groups were sacrificed after 24 h of last treatment. APAP administered group showed a significant rise in the AST, ALT, SALP, LDH, cholesterol, bilirubin, albumin, urea and creatinine in serum which indicated the hepato-renal damage. A significantly enhanced LPO and a depleted level of GSH were observed in APAP intoxicated rats. Declined activities of SOD and Catalase, after acetaminophen exposure indicated oxidative stress in liver and kidney. The activities of ATPase and glucose-6-Phosphatase were significantly inhibited after APAP administration. AuNPs treatment reversed all variables significantly towards normal level and was found nontoxic. Thus it is concluded that gold nanoparticles played a beneficial role in reducing acetaminophen induced toxicity and can be used in the development of drug against hepatic as well as renal diseases, after further preclinical and clinical studies. 相似文献