scholarly journals Analysis of the Efficacy of Metformin Against Doxorubicin Cardiotoxicity and Exploration of its Molecular Mechanism

2022 ◽  
Author(s):  
Jia Wei ◽  
Jin Wei
Keyword(s):  
Molecular Mechanism ◽  
Animal Experiments ◽  
Basic Research ◽  
Protective Role ◽  
The Body ◽  
Retrospective Case ◽  
Doxorubicin Cardiotoxicity ◽  
Important Pathway ◽  
Amp Activated Protein Kinase ◽  
Dose Dependent

Abstract Doxorubicin is a very effective broad-spectrum anti-tumor drug, but it can cause dose-dependent cardiotoxicity and ultimately lead to heart failure. Previous studies have found that metformin exerts a cardioprotective effect through AMP-activated protein kinase (AMPK), but its effect on doxorubicin cardiotoxicity is still unclear. In order to investigate whether and how AMPK affects the ability of metformin to regulate the cardiotoxicity of doxorubicin, we have conducted two parts: clinical research and basic research. We found that metformin can reduce doxorubicin cardiotoxicity through clinical retrospective case-control study. Based on this, animal experiments were conducted to explore the molecular mechanism, and it was found that metformin was not associated with AMPK pathway, an important pathway of energy metabolism in the body, and this pathway did not play a protective role in doxorubicin induced cardiotoxicity. The reason may be related to decreased glucose utilization and mitochondrial autophagy of cardiomyocytes.

scholarly journals Cloning, Expression, and Characterization of a New Glycosaminoglycan Lyase from Microbacterium sp. H14

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 681
Author(s):  
Junhao Sun ◽  
Xu Han ◽  
Guanrui Song ◽  
Qianhong Gong ◽  
Wengong Yu
Keyword(s):  
Enzyme Activity ◽  
Metal Ions ◽  
Animal Experiments ◽  
Basic Research ◽  
Facilitated Diffusion ◽  
Divalent Metal Ions ◽  
Polysaccharide Lyase ◽  
Functional Studies ◽  
Dose Dependent

Glycosaminoglycan (GAG) lyase is an effective tool for the structural and functional studies of glycosaminoglycans and preparation of functional oligosaccharides. A new GAG lyase from Microbacterium sp. H14 was cloned, expressed, purified, and characterized, with a molecular weight of approximately 85.9 kDa. The deduced lyase HCLaseM belonged to the polysaccharide lyase (PL) family 8. Based on the phylogenetic tree, HCLaseM could not be classified into the existing three subfamilies of this family. HCLaseM showed almost the same enzyme activity towards hyaluronan (HA), chondroitin sulfate A (CS-A), CS-B, CS-C, and CS-D, which was different from reported GAG lyases. HCLaseM exhibited the highest activities to both HA and CS-A at its optimal temperature (35 °C) and pH (pH 7.0). HCLaseM was stable in the range of pH 5.0–8.0 and temperature below 30 °C. The enzyme activity was independent of divalent metal ions and was not obviously affected by most metal ions. HCLaseM is an endo-type enzyme yielding unsaturated disaccharides as the end products. The facilitated diffusion effect of HCLaseM is dose-dependent in animal experiments. These properties make it a candidate for further basic research and application.

scholarly journals Protective Role of Myricetin on Markers of Oxidative Stress in Human Erythrocytes Subjected to Oxidative Stress

2009 ◽  
Vol 4 (2) ◽  
pp. 1934578X0900400 ◽  
Author(s):  
Kanti Bhooshan Pandey ◽  
Neetu Mishra ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Protective Role ◽  
Protein Carbonyl ◽  
Human Erythrocytes ◽  
The Body ◽  
Protein Carbonyl Content ◽  
Tert Butylhydroperoxide ◽  
Markers Of Oxidative Stress ◽  
Dose Dependent

The protective effect of myricetin against tert-butylhydroperoxide (t-BHP) induced oxidative stress in human erythrocytes was investigated. Incubating erythrocytes with t-BHP (10−5M) caused development of oxidative stress, as evidenced by significant ( p < 0.05) increase in erythrocyte malondialdedyde (MDA) and protein carbonyl content, and decrease in intracellular reduced glutathione (GSH), membrane sulphydryl (-SH) groups. Incubation of erythrocytes with myricetin, simultaneously with t-BHP, protected the erythrocytes from oxidative stress, an effect which was dose-dependent. The results demonstrate that myricetin attenuates t-BHP induced oxidative damage, suggesting that supplementation of diet with myricetin/myricetin rich food may be beneficial in all pathological conditions where the antioxidant system of the body is overwhelmed.

Amelioration of Carbon Tetrachloride-Induced Liver Injury by Citrus Leaf Extract

2019 ◽  
Vol 17 (4) ◽  
pp. 426-431
Author(s):  
Jin Xuezhu ◽  
Li Jitong ◽  
Nie Leigang ◽  
Xue Junlai
Keyword(s):  
Carbon Tetrachloride ◽  
Leaf Extract ◽  
Hepatic Injury ◽  
The Body ◽  
Dependent Manner ◽  
Weight Changes ◽  
Citrus Leaf ◽  
Dose Dependent ◽  
And Oxidative Stress

The main purpose of this study is to investigate the role of citrus leaf extract in carbon tetrachloride-induced hepatic injury and its potential molecular mechanism. Carbon tetrachloride was used to construct hepatic injury animal model. To this end, rats were randomly divided into 4 groups: control, carbon tetrachloride-treated, and two carbon tetrachloride + citrus leaf extract-treated groups. The results show that citrus leaf extract treatment significantly reversed the effects of carbon tetrachloride on the body weight changes and liver index. Besides, treatment with citrus leaf extract also reduced the levels of serum liver enzymes and oxidative stress in a dose-dependent manner. H&E staining and western blotting suggested that citrus leaf extract could repair liver histological damage by regulating AMPK and Nrf-2.

Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products

2010 ◽  
Vol 3 (3) ◽  
pp. 1057-1064 ◽  
Author(s):  
Kinesh V P ◽  
Neelam D P ◽  
Punit B ◽  
Bhavesh S.B ◽  
Pragna K. S
Keyword(s):  
Diabetes Mellitus ◽  
Oral Delivery ◽  
Proteolytic Enzymes ◽  
Oral Route ◽  
The Body ◽  
Current Status ◽  
Intestinal Lumen ◽  
Insulin Administration ◽  
Novel Approaches ◽  
Dose Dependent

Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible effects, in addition to increased bioavailability.

scholarly journals Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (α-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 315
Author(s):  
Zhenxing Wang ◽  
Zongcai Tu ◽  
Xing Xie ◽  
Hao Cui ◽  
Kin Weng Kong ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Animal Experiments ◽  
Ethyl Acetate Fraction ◽  
The Body ◽  
Total Phenolic ◽  
Antioxidant Power ◽  
Glycogen Accumulation ◽  
Inhibitory Ability

This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid–liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 μg GAE/mg DE) and flavonoid content (455.22 μg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful α-glucosidase inhibitory ability with the IC50 value of 190.03 μg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC50 values of 37.92 and 13.43 μg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.

scholarly journals Early and Late Cytologic Effects of Whole Body Irradiation on Human Marrow

Blood ◽  
1964 ◽  
Vol 23 (4) ◽  
pp. 471-487 ◽  
Author(s):  
T. M. FLIEDNER ◽  
GOULD A. ANDREWS ◽  
EUGENE P. CRONKITE ◽  
VICTOR P. BOND
Keyword(s):  
Dose Group ◽  
Animal Experiments ◽  
Giant Cells ◽  
Whole Body ◽  
High Dose ◽  
Multinucleated Cells ◽  
Exposed Individual ◽  
Interphase Cells ◽  
Cytologic Abnormalities ◽  
Dose Dependent

Abstract 1. Serial marrow studies were performed during the first few days in eight men accidentally exposed to a mixed neutron gamma irradiation. They showed the occurrence of a wave of cytologic abnormalities. These were identical with those seen in animal experiments 1-3 days after whole body irradiation. They were considered to be "mitotically connected" (M. C. Abn.) and included the occurrence of chromosomal bridges and chromosomal fragments in mitoses. In interphase cells, the main abnormalities were nuclear fragments ("karyomeres") in the cytoplasm of erythroblasts, myelocytic cells and lymphocytes; bi- and multinucleated cells; and giant cells. The peak of abnormalities in the erythropoietic forms was reachéd after 2 days; that in the myelopoietic cells 4 days after exposure. On the 4th day, there was a distinct dose-dependent difference in these abnormalities between the high dose group (236-365 rads) and the low dose group (22-68 rads). 2. Some cytologic abnormalities, as seen in increased regeneratory activity of the marrow, were found in marrow smears 3.5 years after the accident, although the peripheral blood counts and mitotic indices of the marrow were within normal range. Their significance is obscure. 3. A careful cytologic evaluation of serially aspirated marrow samples during the first hours and days after whole body exposure proves to be an additional important aid in the assessment of the exposed individual and may well prove to be useful in determining the degree of injury and thus the prognosis.

DOSE-DEPENDENT CHARACTER OF DISTURBANCE OF HEMATOPOIETIC AND IMMUNE SYSTEMS FUNCTION, PRODUCTION OF SOME HORMONES IN EXPERIMENTAL URANIUM ACETATE DIHYDRATE EXPOSURE

2021 ◽  
Vol 1 (1) ◽  
pp. 14-19
Author(s):  
Е. G. Trapeznikova ◽  
V. В. Popov ◽  
A. S. Radilov ◽  
V. V. Shilov
Keyword(s):  
Hematological Parameters ◽  
Chronic Administration ◽  
Absolute Number ◽  
Uranyl Acetate ◽  
The Body ◽  
Acetate Dihydrate ◽  
Functional Changes ◽  
Cd8 Cells ◽  
Tnf Α ◽  
Dose Dependent

The paper presents the results of an experimental study of the dose-dependent nature of functional changes in the body systems under chronic administration of uranyl acetate dihydrate in doses of 0.5 and 5.0 mg/kg per element for 18 weeks. The study was performed on 45 male outbred rats. It has been shown that uranyl acetate dihydrate in a dose of 0.5 mg/kg had no significant effect on hematological parameters. At the same time, activation of bactericidal activity of neutrophils, a decrease in the immunoregulatory index, and an increase in the blood concentration of tumor necrosis factor (TNF-α) have been revealed. The toxicant administered to rats in a dose of 5 mg/kg led to a decrease in the absolute number of erythrocytes, hemoglobin, hematocrit, platelets, the release of myelocytes into the blood, basophilia, monocytosis, the appearance of leukolysis cells and plasmatization of lymphocytes. On the part of the immune system, an increase in the biocidal capacity of neutrophilic granulocytes, TNF-α production, an increase in the number of CD8+ cells, and a reduction in the CD4+/CD8+ ratio have been found. Uranyl acetate dihydrate had a dose-dependent effect only on the number of cytotoxic T-lymphocytes, T-cells with the CD4+CD8+ phenotype, on the immunoregulatory index, and on the level of TNF-α. Hyperglycemia and glucosuria were also dose-dependent. An increase in glucose in the blood and urine indicated a violation of carbohydrate metabolism and kidney function. There was a decrease in the concentration of thyroxine, testosterone and an increase in the level of insulin. Uranyl acetate dihydrate led to the development of insulin resistance. The level of hormones did not depend on the dose of the toxicant administered to the animals.

PROTECTIVE ROLE OF FICUS RACEMOSA IN DIABETES INDUCED NEUROPATHY: STRUCTURAL AND FUNCTIONAL EVIDENCES

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (11) ◽  
pp. 58-60
Author(s):  
N Solanki ◽  
◽  
S. K Bhavsar
Keyword(s):  
Sciatic Nerve ◽  
Diabetic Neuropathy ◽  
Ethanolic Extract ◽  
Protective Role ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Traditional System ◽  
Ficus Racemosa ◽  
Dose Dependent

Ficus racemosa is used in traditional system of medicine for various health problems and diseases, and is commonly known as Gular fig. The main objective was to study its effects against streptozotocin induced diabetic neuropathy by structural and functional marker. Investigation of diabetic neuropathy was carried out through functional and structural assessment in streptozotocin induced in diabetic rats. Diabetic rats were treated for 28 days in dose dependent manner of Ficus racemosa aqueous extract (250 mg/kg and 500 mg/kg) and ethanolic extract (200 mg/kg and 400 mg/kg). Study showed marked protection observed by Ficus racemosa in hippocampus region of brain and sciatic nerve tissues. Ficus racemosa treatment showed improvement in functional and structural markers, which strongly suggest its protective role in diabetic neuropathy.

AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle

2001 ◽  
Vol 280 (5) ◽  
pp. E677-E684 ◽  
Author(s):  
Nicolas Musi ◽  
Tatsuya Hayashi ◽  
Nobuharu Fujii ◽  
Michael F. Hirshman ◽  
Lee A. Witters ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Muscle Contractions ◽  
Treadmill Running ◽  
Dependent Manner ◽  
Rat Skeletal Muscle ◽  
Amp Activated Protein Kinase ◽  
Dose Dependent

The AMP-activated protein kinase (AMPK) has been hypothesized to mediate contraction and 5-aminoimidazole-4-carboxamide 1-β-d-ribonucleoside (AICAR)-induced increases in glucose uptake in skeletal muscle. The purpose of the current study was to determine whether treadmill exercise and isolated muscle contractions in rat skeletal muscle increase the activity of the AMPKα1 and AMPKα2 catalytic subunits in a dose-dependent manner and to evaluate the effects of the putative AMPK inhibitors adenine 9-β-d-arabinofuranoside (ara-A), 8-bromo-AMP, and iodotubercidin on AMPK activity and 3- O-methyl-d-glucose (3-MG) uptake. There were dose-dependent increases in AMPKα2 activity and 3-MG uptake in rat epitrochlearis muscles with treadmill running exercise but no effect of exercise on AMPKα1 activity. Tetanic contractions of isolated epitrochlearis muscles in vitro significantly increased the activity of both AMPK isoforms in a dose-dependent manner and at a similar rate compared with increases in 3-MG uptake. In isolated muscles, the putative AMPK inhibitors ara-A, 8-bromo-AMP, and iodotubercidin fully inhibited AICAR-stimulated AMPKα2 activity and 3-MG uptake but had little effect on AMPKα1 activity. In contrast, these compounds had absent or minimal effects on contraction-stimulated AMPKα1 and -α2 activity and 3-MG uptake. Although the AMPKα1 and -α2 isoforms are activated during tetanic muscle contractions in vitro, in fast-glycolytic fibers, the activation of AMPKα2-containing complexes may be more important in regulating exercise-mediated skeletal muscle metabolism in vivo. Development of new compounds will be required to study contraction regulation of AMPK by pharmacological inhibition.

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