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2.
Front Sociol ; 8: 1219220, 2023.
Article in English | MEDLINE | ID: mdl-37325790

ABSTRACT

[This corrects the article DOI: 10.3389/fsoc.2023.1120288.].

3.
Front Sociol ; 8: 1120288, 2023.
Article in English | MEDLINE | ID: mdl-37143959

ABSTRACT

As the coronavirus pandemic affects virtually every sector of the economy, this ongoing review examines the effects of remote working on women's job performance-including hypotheses about serious activities and how they may balance work and family. In recent years, psychometric testing has become increasingly popular with organizations worldwide, and they are looking at this method to better understand how women achieve balance in their lives. The aim of this work is to investigate how different aspects of psychometrics and factors relating to work-life balance influence women's satisfaction levels. An exploratory factor assessment (EFA) and a confirmatory factor assessment (CFA) using a seven-point Likert scale were performed on data collected from 385 selected female IT workers whose satisfaction levels toward psychometric assessments in their organization were examined. The current study uses EFAs and CFAs to develop and identify the key factors in women's work-life balance. The results also showed that three significant variables accounted for 74% of the variance: 26% from work and family, 24% from personal factors, and 24% from loving their job.

4.
Metabolomics ; 18(7): 51, 2022 07 11.
Article in English | MEDLINE | ID: mdl-35819731

ABSTRACT

OBJECTIVE: Since the COVID-19 pandemic began in early 2020, SARS-CoV2 has claimed more than six million lives world-wide, with over 510 million cases to date. To reduce healthcare burden, we must investigate how to prevent non-acute disease from progressing to severe infection requiring hospitalization. METHODS: To achieve this goal, we investigated metabolic signatures of both non-acute (out-patient) and severe (requiring hospitalization) COVID-19 samples by profiling the associated plasma metabolomes of 84 COVID-19 positive University of Virginia hospital patients. We utilized supervised and unsupervised machine learning and metabolic modeling approaches to identify key metabolic drivers that are predictive of COVID-19 disease severity. Using metabolic pathway enrichment analysis, we explored potential metabolic mechanisms that link these markers to disease progression. RESULTS: Enriched metabolites associated with tryptophan in non-acute COVID-19 samples suggest mitigated innate immune system inflammatory response and immunopathology related lung damage prevention. Increased prevalence of histidine- and ketone-related metabolism in severe COVID-19 samples offers potential mechanistic insight to musculoskeletal degeneration-induced muscular weakness and host metabolism that has been hijacked by SARS-CoV2 infection to increase viral replication and invasion. CONCLUSIONS: Our findings highlight the metabolic transition from an innate immune response coupled with inflammatory pathway inhibition in non-acute infection to rampant inflammation and associated metabolic systemic dysfunction in severe COVID-19.


Subject(s)
COVID-19 , Humans , Inflammation , Metabolomics , Pandemics , RNA, Viral , SARS-CoV-2 , Severity of Illness Index
5.
mSphere ; 6(5): e0066921, 2021 10 27.
Article in English | MEDLINE | ID: mdl-34704776

ABSTRACT

Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility, and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of interleukin 25 (IL-25) and that FMT protected in part by restoring IL-25 signaling. Here, we conducted a prospective study in humans to test if FMT induced IL-25 expression in the colons of patients with recurrent CDI (rCDI). Colonic biopsy specimens and blood were collected at the time of FMT and 60 days later. Colon biopsy specimens were analyzed for IL-25 protein levels, total tissue transcriptome, and epithelium-associated microbiota before and after FMT, and peripheral immune cells were immunophenotyped. FMT increased alpha diversity of the colonic microbiota and levels of IL-25 in colonic tissue. In addition, FMT increased expression of homeostatic genes and repressed inflammatory genes. Finally, circulating Th17 cells were decreased post-FMT. The increase in levels of the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity. IMPORTANCE Fecal microbiota transplantation (FMT) is an effective treatment for C. difficile infection for most patients; however, introducing a complex mixture of microbes also has had unintended consequences for some patients. Attempts to create a standardized probiotic therapeutic that recapitulates the efficacy of FMT have been unsuccessful to date. We sought to understand what immune markers are changed in patients undergoing FMT to treat recurrent C. difficile infection and identified an immune signaling molecule, IL-25, that was restored by FMT. This finding indicates that adjunctive therapy with IL-25 could be useful in treating C. difficile infection.


Subject(s)
Clostridium Infections/therapy , Fecal Microbiota Transplantation , Gastrointestinal Microbiome/physiology , Interleukin-17/metabolism , Aged , Anti-Bacterial Agents/therapeutic use , Clostridioides difficile/drug effects , Clostridioides difficile/pathogenicity , Clostridium Infections/metabolism , Clostridium Infections/microbiology , Colon/pathology , Feces/microbiology , Female , Humans , Inflammation/metabolism , Inflammation/microbiology , Inflammation/therapy , Male , Middle Aged , Prospective Studies , Recurrence , Treatment Outcome
6.
Medicine and Health ; : 17-29, 2019.
Article in English | WPRIM (Western Pacific) | ID: wpr-825528

ABSTRACT

@#Glaukoma adalah sejenis penyakit neurodegeneratif yang berlaku akibat ketidakseimbangan dalam peredaran cecair akues yang disebabkan oleh resistan pada sistem pengaliran keluar cecair tersebut. Ini meningkatkan tekanan intraokular (TIO) yang menyebabkan kerosakan pada saraf optik dan seterusnya mengakibatkan kebutaan yang kekal. Oleh kerana TIO adalah satu faktor risiko glaukoma yang boleh dikawal, ciri-ciri dan variasi tekanan sepanjang 24 jam perlu dikenalpasti sebelum rawatan dimulakan. Pemantauan TIO adalah satu aspek yang terpenting dan kritikal dalam pengurusan glaukoma. Pelbagai tindakan kawalan melalui penggunaan teknologi yang berbeza telah dan sedang dilakukan untuk pemantauan TIO yang kerap dan berterusan selama 24 jam untuk menentukan kewujudan TIO yang tinggi (peak) dan fluktuasi tekanan. Artikel ini bertujuan untuk meninjau pendekatan inovatif yang terkini serta untuk mengulas kepentingan dan kelemahan setiap teknik bagi memperolehi profil TIO selama 24 jam.

7.
Int Immunopharmacol ; 17(2): 254-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23747734

ABSTRACT

Capsaicin (CAP), a constituent of red chilli and red pepper is exposed to exert compelling anticarcinogenic effects. In the present study, we examined the anti-tumorigenic potential of CAP on benzo(a)pyrene-induced mice lung tumorigenesis by analyzing the markers of apoptosis. Intraperitoneal administration of CAP (10mg/kg body weight) to Swiss albino mice suppressed the development of lung carcinoma by amending the protein expressions of apoptotic regulators p53, Bcl-2, Bax and caspase-3. The apoptotic-inducing nature of CAP was further confirmed by DNA agarose gel electrophoresis, transmission electron microscopic study and ethidium bromide/acridine orange staining. The results obtained from the present study show that CAP inhibits the development of mice lung carcinogenesis through its ability to induce apoptosis. Our present findings provide the basis for further clinical exploration of CAP as an anti-carcinogenic compound against lung carcinogenesis.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Capsaicin/administration & dosage , Lung Neoplasms/drug therapy , Lung/drug effects , Animals , Apoptosis , Benzo(a)pyrene/pharmacology , Capsicum/immunology , Carcinogenesis , Caspase 3/metabolism , Cells, Cultured , DNA Fragmentation/drug effects , Injections, Intraperitoneal , Lung/pathology , Lung Neoplasms/chemically induced , Male , Mice , Tumor Suppressor Protein p53/metabolism , bcl-2-Associated X Protein/metabolism
8.
Inflamm Res ; 61(11): 1169-75, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22735861

ABSTRACT

OBJECTIVE: Lung cancer is a serious health problem in most developed countries and its incidence rate is profusely increasing. Capsaicin, a component of red chilli and red pepper has been studied widely for its chemopreventive properties. The aim of the present study is to explore the anti-tumor activity of capsaicin against benzo(a)pyrene-induced lung tumorigenesis in Swiss albino mice. MATERIALS AND METHODS: Benzo(a)pyrene was administered orally (50 mg/kg body weight) to induce lung cancer in Swiss albino mice. Hematological study (hemoglobin content, RBC, WBC count and differential count), histochemical analysis of mast cells and Western blot analysis of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB) were carried out. RESULTS: Hematological parameters and the histochemical analysis of mast cells showed abnormal changes, and the immunoblotting analysis revealed increased protein expression of TNF-α, IL-6, COX-2 and NF-κB in lung cancer-challenged mice administered with benzo(a)pyrene. Capsaicin (10 mg/kg body weight) supplementation to lung cancer bearing mice considerably prevented all the above abnormalities. CONCLUSION: The results of the present study indicate the protective effect of capsaicin against benzo(a)pyrene-induced lung carcinogenesis in mice.


Subject(s)
Antineoplastic Agents/therapeutic use , Capsaicin/therapeutic use , Lung Neoplasms/drug therapy , Animals , Antineoplastic Agents/pharmacology , Benzo(a)pyrene , Blood Cell Count , Capsaicin/pharmacology , Cyclooxygenase 2/immunology , Interleukin-6/immunology , Lung Neoplasms/blood , Lung Neoplasms/chemically induced , Lung Neoplasms/immunology , Male , Mast Cells/cytology , Mast Cells/drug effects , Mice , NF-kappa B/immunology , Tumor Necrosis Factor-alpha/immunology
9.
Indian J Hum Genet ; 17(3): 164-8, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22345987

ABSTRACT

BACKGROUND: Genetic variants of the organic cation transporter (OCT1) gene could influence interindividual variation in clinical response to metformin therapy. The genetic basis for the single-nucleotide polymorphism (SNP) of OCT1 gene has been established in other populations, but it remains to be elucidated in the Indian population. This study is focused on OCT1 gene variants rs2282143 (P341L, 1022C>T), rs628031 (M408V, 1222A>G) and rs622342 (1386C>A) frequency distributions in the South Indian Tamilian population. MATERIALS AND METHODS: A total of 112 unrelated healthy subjects of South Indian Tamilian origin, aged 18-60 years, of either sex were recruited for the study. Genotyping was determined using the quantitative real time-polymerase chain reaction and polymerase chain reaction followed by restriction fragment length polymorphism methods. RESULTS: Allele frequencies of rs2282143, rs628031and rs622342 polymorphisms were 8.9%, 80.3% and 24.5%, respectively. Interethnic differences in the genotype and allele frequencies of OCT1 gene polymorphism were observed when compared with other major populations. The SNPs rs2282143, T allele and rs628031, G allele were more common in Asians (5.5-16.8% and 76.2-81%) and African Americans (8.2% and 73.5%) than in Caucasians (0-2% and 57.4-60%). CONCLUSION: This is the first time the frequency of OCT1 gene polymorphism was determined in the Indian population, and is similar to the frequencies observed in African-Americans and other Asian populations but different from those in Caucasians. The data observed in this study would justify further pharmacogenetic studies to potentially evaluate the role of OCT1 gene polymorphism in the therapeutic efficacy of metformin.

10.
Hum Exp Toxicol ; 30(8): 952-64, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21056953

ABSTRACT

Sirupeellai samoola kudineer (SK), a polyherbal decoction, has been used in Siddha system of medicine for the management of Urolithiasis. Since, there exists no documentation of preclinical toxicological evaluation of SK earlier, in the present study, acute and subacute toxicity of SK was assessed in Sprague Dawley rats as per OECD guideline 423 and 407, respectively. In the acute toxicity study, SK did not produce any toxic signs at a dose level of 50 ml/kg b.wt/p.o. Three doses of SK (4.5, 9.0, 18.0 ml/kg b.wt) were administered and observed for various behavioral, physiological, biochemical, and haematological changes for 28 days in the subacute toxicity study. Low and mid dose of SK (4.5 and 9.0 ml/kg b.wt) did not exhibit any significant physiological and haematological alterations. Whereas, high dose (18.0 ml/kg bw) treatment exhibited significant changes in creatinine, gamma glutamyl transferase (GGT) and acid phosphatase (ACP) levels in serum. Further, histopathological examinations of brain, heart, liver, kidney and sex organs revealed normal architecture signifying no morphological changes upto a dose of 9.0 ml/kg. However, 18.0 ml/kg of SK administration showed few histopathological changes as compared to the control. Based on these results, it can be concluded that Sirupeellai samoola kudineer is safe and non-toxic upto 9.0 ml/kg for 28 days in experimental rats.


Subject(s)
Medicine, Traditional , Plant Extracts/toxicity , Plant Preparations/toxicity , Urolithiasis/drug therapy , Animals , Brain/drug effects , Brain/pathology , Dose-Response Relationship, Drug , Female , India , Kidney/drug effects , Kidney/pathology , Male , Myocardium/pathology , No-Observed-Adverse-Effect Level , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Plant Preparations/isolation & purification , Plant Preparations/therapeutic use , Rats , Rats, Sprague-Dawley , Toxicity Tests, Acute , Toxicity Tests, Subacute
11.
Hum Exp Toxicol ; 29(9): 705-19, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20144955

ABSTRACT

The protective effect of green tea (Camellia sinensis) was tested against arsenic-induced toxicity. However, the possible role of tannins in green tea in alleviating hepatic and renal oxidative injury has also been studied. Administration of sodium arsenite (100 mg/kg/day) for 28 days in Sprague Dawley female rats resulted in significant reduction of biochemical parameters such as delta-aminolevulinic acid dehydratase (ALAD), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and elevation of thiobarbituric acid reactive substances (TBARS) and the index of nitrite/nitrate (NOx) levels. The tissue arsenic burden was increased after arsenic exposure for a period of 28 days. Green tea crude fraction (GTC) co-treated with sodium arsenite for 28 days caused significant (p < .01) elevation of ALAD, GSH, GPx, SOD, and nitrate/nitrite levels and reduction of the TBARS level and tissue burden when compared to detannified green tea fraction (GTDT)-treated groups. The protective role of tannin-rich fraction of C. sinensis when compared to the detannified fraction was also confirmed by histological examinations. The greater activity of GTC than that of detannified green tea fraction correlates with the higher content of tannins in green tea. Overall, these results indicate that the tannin-rich green tea could have improved the defense mechanism against arsenic-induced oxidative stress and reduced the tissue arsenic burden.


Subject(s)
Arsenic/analysis , Arsenic/toxicity , Camellia sinensis/chemistry , Kidney/chemistry , Liver/chemistry , Protective Agents/therapeutic use , Tannins/therapeutic use , Animals , Arsenic/administration & dosage , Arsenic Poisoning/drug therapy , Arsenites/administration & dosage , Arsenites/toxicity , Biomarkers/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Dose-Response Relationship, Drug , Female , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Liver/drug effects , Liver/metabolism , Liver/pathology , Oxidative Stress/drug effects , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Porphobilinogen Synthase/metabolism , Protective Agents/chemistry , Protective Agents/isolation & purification , Random Allocation , Rats , Rats, Sprague-Dawley , Renal Insufficiency/chemically induced , Renal Insufficiency/prevention & control , Sodium Compounds/administration & dosage , Sodium Compounds/toxicity , Tannins/analysis , Tannins/isolation & purification
12.
Biol Trace Elem Res ; 138(1-3): 212-25, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20165931

ABSTRACT

Copper is known as Gunma Kaalan in Siddha literature, which means that the drug is effective for healing ulcers. The herbomineral drug "Thamira parpam" is prepared by calcining the purified copper foils with rock salt, lime juice, bracteated birth wort juice, and Alangium root decoction according to Siddha medicine. Our study investigated the possible role of Thamira parpam (TP) in the management of cysteamine-induced duodenal ulcers. Cysteamine (400 mg kg(-1) body weight(-1), two doses at 4 h interval) orally given to rats resulted in high ulcer index, increased TBARS with concomitant depletion of antioxidants such as superoxide dismutase, glutathione, glutathione peroxidase, and inflammatory markers cathepsin D, and myeloperoxidase (p < 0.01). Herbomineral drug TP (0.5, 1, and 2 mg/kg, p.o.) challenged with cysteamine attenuated the elevation of TBARS and imbalance of antioxidants. In the increases in liver inflammatory markers, tissue histopathology changes were not severe in TP treatment. Positive control omeprazole (25 mg/kg, body weight, orally) showed considerable protection against anomaly in biochemical parameters and tissue histology. Hence, our results indicate that the attenuation of oxidative stress by the herbomineral drug in experimentally induced damage to liver and duodenum of rats could be mediated by free radical quenching property.


Subject(s)
Cysteamine/toxicity , Duodenal Ulcer/chemically induced , Duodenum/metabolism , Liver/metabolism , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Animals , Body Weight/drug effects , Cathepsin D/metabolism , Duodenal Ulcer/metabolism , Duodenum/drug effects , Glutathione/metabolism , Lipid Peroxidation/drug effects , Liver/drug effects , Peroxidase/metabolism , Radiation-Protective Agents/toxicity , Rats , Superoxide Dismutase/metabolism
13.
Nat Prod Res ; 23(8): 763-74, 2009.
Article in English | MEDLINE | ID: mdl-19418359

ABSTRACT

In the present study, we have assessed the chemopreventive effect of capsaicin (CAP) on glucose metabolism with reference to blood glucose and liver glycogen levels, key glycolytic, and gluconeogenic enzymes along with electron transport chain (ETC) complexes during benzo(a)pyrene (B(a)P)-induced lung cancer in Swiss albino mice. B(a)P (50 mg kg(-1) body weight)-induced lung cancer animals showed marked decline in blood glucose levels, glycogen levels, elevations in the activities of key glycolytic enzymes (hexokinase, phosphoglucoisomerase and aldolase), and gluconeogenic enzymes (glucose-6-phosphatase and fructose-6-phosphatase) together with a decrease in the activities of ETC complexes. Supplementation of CAP (10 mg kg(-1) body weight) inhibited all the above alterations during lung cancer and restored near normalcy. Histochemical analysis by periodic acid Schiff's staining further confirmed the biochemical findings that highlighted the chemopreventive action of CAP during B(a)P-induced experimental lung tumourigenesis.


Subject(s)
Antipruritics/pharmacology , Blood Glucose/drug effects , Capsaicin/pharmacology , Lung Neoplasms/chemically induced , Lung Neoplasms/drug therapy , Animals , Benzo(a)pyrene/pharmacology , Fructose-Bisphosphatase/metabolism , Glycogen/metabolism , Liver/drug effects , Liver/metabolism , Lung/drug effects , Lung/metabolism , Lung/pathology , Lung Neoplasms/metabolism , Male , Mice , Phosphoric Monoester Hydrolases/metabolism
14.
Eur J Clin Nutr ; 63(10): 1206-12, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19471290

ABSTRACT

BACKGROUND/OBJECTIVES: There is a high prevalence of diabetes mellitus associated with insulin resistance in Indian adults, probably due to an inappropriately high accumulation of body fat at lower body mass indices (BMIs, kg/m(2)), as well as to a lower skeletal muscle mass. Although skeletal muscle is an important site of glucose disposal, the strength of its association with insulin sensitivity (IS) is unknown in the Indian population. SUBJECTS/METHODS: This was a cross-sectional study performed to assess the association of body fat, muscle and muscle function with IS in 51 young, healthy, nonobese Indian men with BMI ranging from 15 to 25 kg/m(2), using hyperinsulinemic euglycemic clamp method. RESULTS: The median IS was 5.32 (mg/(kg min))/(microU/ml), lower, upper quartile, 4.03, 6.56); (SI units: 4.25, lower, upper quartile, 3.22, 5.24 (micromol/(kg min))/(pmol/l)). A multiple linear regression of the natural log transformed value of IS on BMI and body muscle mass measured as the appendicular lean soft tissue (expressed as a percentage of body weight) explained 49% of the variance in IS. Independently, body fat percent and muscle (handgrip) strength showed significant bivariate correlations with IS (rho=-0.61, P<0.001; rho=0.32, P=0.027, respectively), although these variables did not enter into the multiple regression. CONCLUSIONS: BMI and body fat have been shown to be inversely related to IS at higher BMIs. This study indicates that a relative increase in BMI and reduced muscle mass and possibly function are also associated with reduced IS in lean Indian men.


Subject(s)
Asian People , Body Composition/physiology , Insulin Resistance , Insulin/metabolism , Muscle, Skeletal/physiology , Absorptiometry, Photon , Adolescent , Adult , Blood Glucose/metabolism , Body Mass Index , Calorimetry, Indirect , Glucose Clamp Technique , Humans , Male , Muscle Strength/physiology , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/metabolism , Oxygen Consumption , Young Adult
15.
Mol Cell Biochem ; 331(1-2): 135-43, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19449198

ABSTRACT

Lung cancer is currently a leading cause of death all over the world. Environmental risk factors, particularly genotoxic chemicals such as polycyclic aromatic hydrocarbons (PAH), are likely to account for a much higher mortality. Xenobiotic metabolizing enzymes are potentially chief determinants in both the susceptibility to the mutagenic effects of chemical carcinogens and in the response of tumors to chemotherapy. The well-known carcinogen benzo(a)pyrene (B(a)P) of PAH family was given orally (50 mg/kg body weight) to induce lung cancer in Swiss albino mice. B(a)P induction altered the levels of cytochromes (P450, b5), activities of phase I biotransformation enzymes (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase and epoxide hydrolase), phase II enzymes (glutathione-S-transferase, UDP-glucuronyl transferase and DT-diaphorase), and the levels of serum tumor markers. Treatment with capsaicin (CAP) (10 mg/kg body weight) to the lung carcinoma mice restored back the activities of phase I and II biotransformation enzymes and the levels of tumor markers to near normalcy. The above findings were substantiated by immunoblotting and immunohistochemical analysis of cytochrome P450 1A1 (CYP1A1) in the lung tissues. Our present study unravels that CAP can effectively detoxify the carcinogens which discloses its anti-carcinogenic effect during experimental lung cancer.


Subject(s)
Biomarkers, Tumor/blood , Capsaicin/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/enzymology , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/enzymology , Xenobiotics/metabolism , Animals , Capsaicin/pharmacology , Cytochrome P-450 CYP1A1/metabolism , Cytochromes b5/metabolism , Drug Screening Assays, Antitumor , Immunohistochemistry , Lung/drug effects , Lung/enzymology , Lung/pathology , Lung Neoplasms/blood , Male , Metabolic Detoxication, Phase I , Metabolic Detoxication, Phase II , Mice , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Neoplasms, Experimental/blood
16.
Cell Prolif ; 42(2): 229-40, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19317806

ABSTRACT

OBJECTIVES: The aim of this study was to investigate mechanisms involved in the growth inhibitory effect of silymarin, in humanhepatocellular carcinoma. MATERIALS AND METHODS: The human hepatocellular carcinoma cell line HepG2 was utilized and the MTT assay was performed to study the antiproliferative effect of silymarin. Dual staining was undertaken for ethidium bromide/acridine orange, propidium iodide staining and DNA fragmentation studies were executed to confirm the presence of apoptosis. Cell-cycle analysis was revealed by flow cytometry and mitochondrial transmembrane potential was measured by uptake of the mitochondrial-specific lipophilic cationic dye rhodamine 123. Western blotting analysis for cytochrome c, p53, Bax, Bcl-2, APAF-1, caspase-3, survivin, beta-catenin, cyclin D1, c-Myc and PCNA was carried out. RESULTS: Silymarin inhibited population growth of the hepatocellular carcinoma cells in a dose-dependent manner, and the percentage of apoptotic cells was increased after treatment with 50 and 75 microg/ml silymarin for 24 h. Silymarin treatment increased the proportion of cells with reduced DNA content (sub-G(0)/G(1) or A(0) peak), indicative of apoptosis with loss of cells in the G(1) phase. Silymarin also decreased mitochondrial transmembrane potential of the cells, thereby increasing levels of cytosolic cytochrome c while up-regulating expression of pro-apoptotic proteins (such as p53, Bax, APAF-1 and caspase-3) with concomitant decrease in anti-apoptotic proteins (Bcl-2 and survivin) and proliferation-associated proteins (beta-catenin, cyclin D1, c-Myc and PCNA). CONCLUSIONS: Our results demonstrate that silymarin treatment inhibited proliferation and induced apoptosis in the human hepatocellular carcinoma cell line HepG2.


Subject(s)
Apoptosis/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Silymarin/pharmacology , Apoptotic Protease-Activating Factor 1/metabolism , Caspase 3/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Nucleus/drug effects , Cell Proliferation/drug effects , Cyclin D1/metabolism , Cytochromes c/metabolism , DNA Fragmentation/drug effects , Dose-Response Relationship, Drug , Flavonoids/pharmacology , Gene Expression/drug effects , Humans , Inhibitor of Apoptosis Proteins , Liver Neoplasms/metabolism , Membrane Potential, Mitochondrial/drug effects , Microtubule-Associated Proteins/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Proliferating Cell Nuclear Antigen/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Survivin , Tumor Suppressor Protein p53/metabolism , bcl-2-Associated X Protein/metabolism , beta Catenin/metabolism
17.
Arch Pharm Res ; 32(2): 229-34, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19280153

ABSTRACT

Spices and vegetables possess antioxidant activity that can be applied for preservation of lipids and lower lipid peroxidation in biological systems. In the present study, we have investigated the effect of capsaicin on lipid metabolism during benzo(a)pyrene induced lung cancer in Swiss albino mice. Benzo(a)pyrene (50 mg/kg wt) induced lung cancer animals showed abnormal changes in the tissue and serum lipids, lipoproteins and lipid metabolizing enzymes. Treatment with capsaicin (10 mg/kg body wt) remarkably attenuated all the above alterations and restored normalcy. These findings reveal the chemomodulatory potential of capsaicin in attenuating the alterations in lipid metabolism during experimental lung carcinogenesis.


Subject(s)
Capsaicin/therapeutic use , Lipid Metabolism/drug effects , Lung Neoplasms/metabolism , Animals , Benzo(a)pyrene , Capsaicin/administration & dosage , Lipid Peroxidation/drug effects , Lipids/blood , Lung/drug effects , Lung/enzymology , Lung/metabolism , Lung Neoplasms/blood , Male , Mice
18.
Fundam Clin Pharmacol ; 23(1): 97-103, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19207542

ABSTRACT

The objective of the present study was to investigate whether lysosome is a target in benzo(a)pyrene-induced, oxidative stress-mediated lung cancer in Swiss albino mice and the plausible role of the phytochemical substance capsaicin in mitigating lysosomal damage. Oxidative stress was assessed based on the level of carbonyl content. The activities of lysosomal proteases like cathepsin-D, cathepsin-B, beta-D-glucosidase, beta-D-galactosidase, beta-D-glucuronidase, beta-D-N-acetylglucosaminidase and acid phosphatase were assessed to evaluate lysosomal function. Administration of benzo(a)pyrene (50 mg/kg body weight) to mice induced a increase in the activities of lysosomal enzymes and oxidative stress was evident by the increase in carbonyl content. Treatment with capsaicin (10 mg/kg body weight) decreased carbonyl content and restored the activities of lysosomal enzymes to near normalcy. Transmission electron microscopic study of lysosomes further showed the defensive action of capsaicin against the lysosomal damage caused in benzo(a)pyrene-induced lung cancer. From the present study, it can be concluded that lysosomal damage is an indispensable event in benzo(a)pyrene-induced lung cancer, and capsaicin was able to effectively prevent it, which proves the chemoprotective effect of capsaicin against benzo(a)pyrene-induced experimental lung carcinogenesis.


Subject(s)
Benzo(a)pyrene/toxicity , Capsaicin/pharmacology , Lung Neoplasms/prevention & control , Lysosomes/drug effects , Animals , Anticarcinogenic Agents/pharmacology , Carcinogens/toxicity , Lung Neoplasms/chemically induced , Lysosomes/enzymology , Male , Mice , Microscopy, Electron, Transmission , Oxidative Stress/drug effects , Peptide Hydrolases/drug effects , Peptide Hydrolases/metabolism
19.
J Pharm Pharmacol ; 60(6): 803-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18498718

ABSTRACT

This study was designed to examine the impact of a principal component of hot red peppers and chilli peppers, capsaicin, on alterations in lipid peroxidation, membrane-bound enzyme profiles and glycoprotein levels during benzo(a)pyrene (BP)-induced lung cancer in Swiss albino mice. BP (50 mgkg(-1)) induced deleterious changes that were that revealed by alterations in lipid peroxidation, membrane-bound enzyme (Na+/K+ ATPase, Ca2+ ATPase and Mg2+ ATPase) activity, levels of total protein and protein-bound carbohydrate components (sialic acid, hexose, hexosamine, hexuronic acid and fucose). Pre-co-treatment with capsaicin (10 mg kg(-1)) restored the detrimental effects induced by BP, indicating its protective role in BP-induced lung cancer.


Subject(s)
Anticarcinogenic Agents/pharmacology , Capsaicin/pharmacology , Cell Membrane/drug effects , Lung Neoplasms/prevention & control , Animals , Benzo(a)pyrene/toxicity , Ca(2+) Mg(2+)-ATPase/drug effects , Ca(2+) Mg(2+)-ATPase/metabolism , Calcium-Transporting ATPases/drug effects , Calcium-Transporting ATPases/metabolism , Carcinogens/toxicity , Cell Membrane/enzymology , Glycoproteins/drug effects , Glycoproteins/metabolism , Lipid Peroxidation/drug effects , Lung Neoplasms/chemically induced , Male , Mice , Sodium-Potassium-Exchanging ATPase/drug effects , Sodium-Potassium-Exchanging ATPase/metabolism
20.
Phytother Res ; 22(4): 529-33, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18338764

ABSTRACT

The effect of a pungent ingredient of red pepper, capsaicin, on oxidative stress induced changes in the antioxidant defense system by benzo(a)pyrene in the lungs of mice was studied. Oral gavage administration of benzo(a)pyrene (50 mg/kg body weight) to mice led to a marked increase in oxidative stress indicated by alterations in pulmonary lipid peroxidation, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Pre-co-treatment with capsaicin (10 mg/kg body weight i.p.) restored cellular normalcy, highlighting the antioxidant potential of capsaicin in mitigating the oxidative stress mediated damage produced during benzo(a)pyrene-induced lung cancer.


Subject(s)
Antioxidants/metabolism , Capsaicin/pharmacology , Lung Neoplasms/prevention & control , Lung/drug effects , Animals , Ascorbic Acid/metabolism , Benzo(a)pyrene , Catalase/metabolism , Glucosephosphate Dehydrogenase/metabolism , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Glutathione Transferase/metabolism , Lipid Peroxidation/drug effects , Lung/metabolism , Lung/pathology , Lung Neoplasms/chemically induced , Lung Neoplasms/metabolism , Male , Mice , Oxidative Stress/drug effects , Superoxide Dismutase , Vitamin A/metabolism , Vitamin E/metabolism
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