scholarly journals Biological Evaluation of Polyherbal Ayurvedic Cardiotonic Preparation “Mahamrutyunjaya rasa”

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Pallavi D. Rai ◽  
Sadhana J. Rajput
Keyword(s):  
Uric Acid ◽  
Cell Viability ◽  
Serum Levels ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Toxicological Evaluation ◽  
Cytotoxic Effects ◽  
Alkaline Phosphotase ◽  
Liquid Chromatographic Analysis ◽  
Liquid Chromatographic

Mahamrutyunjaya rasa(MHR), an Ayurvedic formulation, used as cardiotonic, contains potentially toxic compounds like aconitine, which are detoxified during preparation using traditional methods. Comparative toxicological evaluation of laboratory prepared formulation (F1) and two marketed formulations (F2 and F3) were performed based on their effects on viability of H9c2 cells and after single oral dose administration in mice. Cardioprotective effect of formulations at 25 and 50 mg/kg doses were studied in isoproterenol- (ISO-) induced myocardial infarcted rats. F1 and F2 did not affect the cell viability, while F3 decreased the cell viability in concentration and time-dependent manner. Rats administered with ISO showed significant increase in the serum levels of glutamate oxaloacetate transaminase, alkaline phosphotase, creatinine kinase isoenzymes, lactate dehydrogenase, and uric acid, while F1 and F2 treatment showed significant reduction in the same. F3 showed further increase in the serum levels of enzymes and uric acid in ISO-challenged rats. High pressure liquid chromatographic analysis of formulations showed higher concentration of aconitine in F3. Study shows that F1 and F2 possess cardioprotective property with higher safety, while formulation F3 cannot be used as cardioprotective due to its cytotoxic effects. Thus, proper quality assessment methods are required during preparation of traditional formulations.

scholarly journals Cytotoxic Effects of Air Freshener Biocides in Lung Epithelial Cells

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800
Author(s):  
Jung-Taek Kwon ◽  
Mimi Lee ◽  
Gun-Baek Seo ◽  
Hyun-Mi Kim ◽  
Ilseob Shim ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epithelial Cells ◽  
Cell Viability ◽  
Lung Epithelial Cells ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cytotoxic Effects ◽  
Lung Epithelial ◽  
Dose Dependent ◽  
A549 Lung

This study evaluated the cytotoxicity of mixtures of citral (CTR) and either benzisothiazolinone (BIT, Mix-CTR-BIT) or triclosan (TCS, Mix-CTR-TCS) in human A549 lung epithelial cells. We investigated the effects of various mix ratios of these common air freshener ingredients on cell viability, cell proliferation, reactive oxygen species (ROS) generation, and DNA damage. Mix-CTR-BIT and Mix-CTR-TCS significantly decreased the viability of lung epithelial cells and inhibited cell growth in a dose-dependent manner. In addition, both mixtures increased ROS generation, compared to that observed in control cells. In particular, cell viability, growth, and morphology were affected upon increase in the proportion of BIT or TCS in the mixture. However, comet analysis showed that treatment of cells with Mix-CTR-BIT or Mix-CTR-TCS did not increase DNA damage. Taken together, these data suggested that increasing the content of biocides in air fresheners might induce cytotoxicity, and that screening these compounds using lung epithelial cells may contribute to hazard assessment.

scholarly journals Rule of UA on Cardiac Myocytes Uric Acid Differently Influence the Oxidative Damage Induced by Acute Exposure of High Level of Glucose in Chicken Cardiac Myocytes

2020 ◽  
Vol 7 ◽  
Author(s):  
Xiaolong Sun ◽  
Hongchao Jiao ◽  
Jingpeng Zhao ◽  
Xiaojuan Wang ◽  
Hai Lin
Keyword(s):  
Uric Acid ◽  
Oxidative Damage ◽  
Cell Viability ◽  
Cardiac Myocytes ◽  
High Glucose ◽  
Acute Exposure ◽  
Related Factor ◽  
Mrna Levels ◽  
Dependent Manner ◽  
High Level

Background: Uric acid (UA) is a potent scavenger of oxidants in mammalian and avian species. In humans, hyperglycemia with simultaneous hyperuricemia may exert additional damage to the cardiovascular system. Chickens naturally have hyperglycemia (10.1–11.0 mmol/L) and hyperuricemia (100–900 μmol/L), which makes them an interesting model.Methods: The aim of this study was to investigate the effects of UA on the oxidative damage induced by acute exposure of high level of glucose in chicken cardiac myocytes.Results: Cell viability and the concentrations of thiobarbituric acid reactive substance (TBARS) were decreased by glucose treatment in a dose- and time-dependent manner. After acute exposure to high level of glucose (300 mM), a moderate level of UA (300 μM) increased cell viability and reduced TBARS and glutathione (GSH) content. Compared to the control or to independent high glucose (300 mM) or UA (1,200 μM) treatment, the concurrent treatment of high glucose and high UA significantly increased the TBARS, protein carbonyl contents, and ROS concentration, whereas it decreased the cell viability, superoxide dismutase (SOD) activity, and GSH content. In the presence of high glucose and UA, the nucleic protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was decreased and the mRNA levels of the genes cat, sod1, sod2, gss, and gclc were downregulated.Conclusion: In conclusion, acute exposure of high level of glucose induced oxidative damage in the cardiac myocytes of chicken. The present result suggests that an adequate level of uric acid is helpful in alleviating the acute oxidative damage that is induced by high glucose, whereas the inhibition of the Nrf2 pathway by a high level of uric acid may render the cardiac myocytes more vulnerable to suffering from oxidative damage.

Biological Evaluation and Molecular Modeling of 3,4-dihydropyrimidine- 2(1H)-one Derivatives as Cytotoxic Agents on Breast Cancer In Vitro

2020 ◽  
Vol 17 (8) ◽  
pp. 983-992
Author(s):  
Hoda Sharifi ◽  
Ahmad Ebadi ◽  
Meysam Soleimani
Keyword(s):  
Molecular Modeling ◽  
Anticancer Agents ◽  
Antitumor Agents ◽  
Biological Evaluation ◽  
Cytotoxic Agents ◽  
Polymerization Process ◽  
Dependent Manner ◽  
Cytotoxic Effects ◽  
Receptor Complexes ◽  
Amide Derivatives

Background: Kinesins and tubulin inhibitors have attracted researchers’ attention as hopeful targets for achieving effective anticancer agents. Dihydropyrimidine-2-ones (DHPMs) inhibit motor proteins Eg5 in the polymerization process of tubulin, also scaffold bearing benzothiazole heterocycle can block tubulin polymerization/depolymerization. Objective: In this study, the cytotoxic effects and molecular modeling of newly synthesized derivatives of DHPM that were designed by the Scaffold-hopping approach were investigated as potential dual-inhibitors of Eg5 and tubulin. Methods: We investigated the cytotoxic effects of DHPMs derivatives by MTT assay and measureing the Caspase 3 activity. Also, molecular modeling studies were performed by AutoDock4 and GROMACS 4.5.6. Results: According to the results, the d2 derivative (IC50 = 68.58 ± 7, SI = 2.57) eliminates MDA-MB- 231 cells in a dose-dependent manner through caspase-dependent and caspase-independent cell death pathways. Molecular docking studies revealed that the d2 compound could interact with both Eg5 and tubulin key residues. MD simulation also demonstrated the stability of the studied ligand-receptor complexes during the 30 ns of the production run. The effectiveness of substitutions at C4 of the DHPM ring was obtained 4-acetoxy-phenyl, 4-methoxyphenyl, and 4-nitrophenyl, respectively. Conclusion: The findings of the present study provide evidence that DHPM C5 amide derivatives bearing benzothiazole ring might be considered as promising lead compounds for the discovery of novel and multi-target antitumor agents.

scholarly journals Toxicological evaluation of flumequine in pubertal male rats after oral administration for six weeks

2018 ◽  
Vol 62 (1) ◽  
pp. 87-96
Author(s):  
JeongWoo Kang ◽  
Md Akil Hossain ◽  
Byungkook Choi ◽  
Joon-Hyoung Cho ◽  
Seok-Jin Kang ◽  
...  
Keyword(s):  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Male Rats ◽  
Dependent Manner ◽  
Free Triiodothyronine ◽  
Toxicological Evaluation ◽  
Toxicological Effects ◽  
Thyroid Glands ◽  
Pituitary Glands ◽  
The Brain

AbstractIntroductionVeterinarians use flumequine (FLU) widely but its toxicological effects are still unclear.Material and MethodsFLU doses of 53, 200, or 750 mg/kg were administered orally for six weeks to pubertal male rats for evaluation of their toxicity.ResultsWeight gain was poorer after seven days of exposure to FLU 750, but relative weights of the brain, adrenal and thyroid glands, and testes were notably higher. Haematological and lipid profile parameters, cardiac markers, and inorganic phosphate significantly increased in the FLU 750 group. Blood glucose, oestradiol and serum concentrations of immunoglobulins G (IgG) and E (IgE) significantly decreased after treatment. The levels of interleukins 10 (IL-10) and 6 (IL-6) fell significantly in the FLU 200 and FLU 750 groups. Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and cyclooxygenase-2 (Cox-2) expression amplified after treatment. Serum levels of free triiodothyronine (fT3) and free thyroxine (fT4) reduced in the FLU 200 and FLU 750 groups without changes in total T3 or T4 level. All doses of FLU significantly depressed concentrations of thyroid-stimulating hormone (TSH) and testosterone. Histopathology of thyroid glands from rats treated with FLU 750 showed degeneration and depletion of thyroid follicular epithelial cells. Expression of 8-hydroxydeoxyguanosine (8-OHdG) was increased in a dose-dependent manner in the brain, but decreased in the testes. Expression of CYP1A1 increased in the adrenal and pituitary glands.ConclusionThe results of this study suggest that the toxicity of FLU in rats is an effect of its disruptive influence on the pituitary-thyroid hormonal system and on the dysfunction of the immune system.

scholarly journals Zurampic Protects Pancreatic β-Cells from High Uric Acid Induced-Damage by Inhibiting URAT1 and Inactivating the ROS/AMPK/ERK Pathways

2018 ◽  
Vol 47 (3) ◽  
pp. 1074-1083 ◽  
Author(s):  
Ying Xin ◽  
Kun Wang ◽  
Zhaotong Jia ◽  
Tao Xu ◽  
Qiang Xu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Cell Viability ◽  
Mrna Expression ◽  
Caspase 3 ◽  
Dependent Manner ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Underlying Mechanisms ◽  
High Level ◽  
High Uric Acid

Background/Aims: Zurampic is a US FDA approved drug for treatment of gout. However, the influence of Zurampic on pancreatic β-cells remains unclear. The study aimed to evaluate the effects of Zurampic on high uric acid-induced damage of pancreatic β-cells and the possible underlying mechanisms. Methods: INS-1 cells and primary rat islets were stimulated with Zurampic and the mRNA expression of urate transporter 1 (URAT1) was assessed by qRT-PCR. Cells were stimulated with uric acid or uric acid plus Zurampic, and cell viability, apoptosis and ROS release were measured by MTT and flow cytometry assays. Western blot analysis was performed to evaluate the expressions of active Caspase-3 and phosphorylation of AMPK and ERK. Finally, cells were stimulated with uric acid or uric acid plus Zurampic at low/high level of glucose (2.8/16.7 mM glucose), and the insulin release was assessed by ELISA. Results: mRNA expression of URAT1 was decreased by Zurampic in a dose-dependent manner. Uric acid decreased cell viability, promoted cell apoptosis and induced ROS release. Uric acid-induced alterations could be reversed by Zurampic. Activation of Caspase-3 and phosphorylation of AMPK and ERK were enhanced by uric acid, and the enhancements were reversed by Zurampic. Decreased phosphorylation of AMPK and ERK, induced by Zurampic, was further reduced by adding inhibitor of AMPK or ERK. Besides, uric acid inhibited high glucose-induced insulin secretion and the inhibition was rescued by Zurampic. Conclusions: Zurampic has a protective effect on pancreatic β-cells against uric acid induced-damage by inhibiting URAT1 and inactivating the ROS/AMPK/ERK pathway.

Vitamin D Supplementation and Serum Levels of Magne-sium and Selenium in Type 2 Diabetes Mellitus Patients: Gender Dimorphic Changes

2014 ◽  
Vol 84 (1-2) ◽  
pp. 27-34 ◽  
Author(s):  
Nasser M. Al-Daghri ◽  
Khalid M. Alkharfy ◽  
Nasiruddin Khan ◽  
Hanan A. Alfawaz ◽  
Abdulrahman S. Al-Ajlan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Serum Levels ◽  
Vitamin D Supplementation ◽  
Serum Selenium ◽  
Dependent Manner

The aim of our study was to evaluate the effects of vitamin D supplementation on circulating levels of magnesium and selenium in patients with type 2 diabetes mellitus (T2DM). A total of 126 adult Saudi patients (55 men and 71 women, mean age 53.6 ± 10.7 years) with controlled T2DM were randomly recruited for the study. All subjects were given vitamin D3 tablets (2000 IU/day) for six months. Follow-up mean concentrations of serum 25-hydroxyvitamin D [25-(OH) vitamin D] significantly increased in both men (34.1 ± 12.4 to 57.8 ± 17.0 nmol/L) and women (35.7 ± 13.5 to 60.1 ± 18.5 nmol/L, p < 0.001), while levels of parathyroid hormone (PTH) decreased significantly in both men (1.6 ± 0.17 to 0.96 ± 0.10 pmol/L, p = 0.003) and women (1.6 ± 0.17 to 1.0 ± 0.14 pmol/L, p = 0.02). In addition, there was a significant increase in serum levels of selenium and magnesium in men and women (p-values < 0.001 and 0.04, respectively) after follow-up. In women, a significant correlation was observed between delta change (variables at six months-variable at baseline) of serum magnesium versus high-density lipoprotein (HDL)-cholesterol (r = 0.36, p = 0.006) and fasting glucose (r = - 0.33, p = 0.01). In men, there was a significant correlation between serum selenium and triglycerides (r = 0.32, p = 0.04). Vitamin D supplementation improves serum concentrations of magnesium and selenium in a gender-dependent manner, which in turn could affect several cardiometabolic parameters such as glucose and lipids.

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