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1.
Bioorg Chem ; 88: 102937, 2019 07.
Article in English | MEDLINE | ID: mdl-31048120

ABSTRACT

Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.


Subject(s)
Antineoplastic Agents/pharmacology , Butylamines/pharmacology , Spermidine/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Butylamines/chemical synthesis , Butylamines/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Cricetinae , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Hep G2 Cells , Humans , Molecular Structure , Spermidine/chemical synthesis , Spermidine/chemistry , Structure-Activity Relationship , Wound Healing/drug effects
2.
Environ Res ; 162: 35-40, 2018 04.
Article in English | MEDLINE | ID: mdl-29276977

ABSTRACT

Although studies have examined leaching of bisphenol A (BPA) from dental sealants into saliva, occurrence of BPA, bisphenol A diglycidyl ether (BADGE), and their derivatives in dental sealants themselves has not been investigated. In this study, concentrations of eight bisphenol analogues (BPs), BADGE and its derivatives (BADGEs), including BADGE‧H2O, BADGE‧HCl, BADGE‧2H2O, BADGE‧2HCl, and BADGE‧H2O‧HCl, were determined in 70 dental sealants collected from the U.S. market. Of the 70 dental sealants analyzed, 65 contained at least one of the target chemicals measured. BADGE‧2H2O was the most abundant compound, found at concentrations of up to 1780µg/g. The geometric mean (GM) concentration of total BADGEs was 47.8µg/g, which was two to three orders of magnitude higher than that of total BPs (GM: 539ng/g). BPA was found in 46% of the sealants and BADGEs was found in 87% of the sealants analyzed. Majority of the dental sealants analyzed in this study were manufactured in the United States and Korea; no significant differences were observed in the concentrations of BPs and BADGEs between the two countries. An exposure assessment was made based on the concentrations of BPs and BADGEs measured in sealants and their application rates in dentistry. The worst-case exposure scenario with the highest measured concentration of total BPs and BADGEs and application on 8 teeth at 8mg each yielded an estimated daily intake (EDI) of 1670 and 5850ng/kg·bw/day for adults and children, respectively. Although the EDI is below the specific migration limit set by the European Food Safety Authority, dental sealants are a source of exposure to BPs and BADGEs, especially in children.


Subject(s)
Benzhydryl Compounds , Environmental Exposure , Epoxy Compounds , Phenols , Pit and Fissure Sealants , Adult , Benzhydryl Compounds/analysis , Child , Epoxy Compounds/analysis , Humans , Phenols/analysis , Republic of Korea
3.
Cardiovasc Diabetol ; 15: 27, 2016 Feb 09.
Article in English | MEDLINE | ID: mdl-26861446

ABSTRACT

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM). To identify the most effective treatment for CVD, it is paramount to understand the mechanism behind cardioprotective therapies. Although metformin has been shown to reduce CVD in Type-2 DM clinical trials, the underlying mechanism remains unexplored. CD34(+) cell-based therapies offer a new treatment approach to CVD. The aim of this study was to investigate the effect of metformin on the angiogenic properties of CD34(+) cells under conditions mimicking acute myocardial infarction in diabetes. METHODS: CD34(+) cells were cultured in 5.5 or 16.5 mmol/L glucose ± 0.01 mmol/L metformin and then additionally ± 4 % hypoxia. The paracrine function of CD34(+) cell-derived conditioned medium was assessed by measuring pro-inflammatory cytokines, vascular endothelial growth factor A (VEGFA), and using an in vitro tube formation assay for angiogenesis. Also, mRNA of CD34(+) cells was assayed by microarray and genes of interest were validated by qRT-PCR. RESULTS: Metformin increased in vitro angiogenesis under hyperglycemia-hypoxia and augmented the expression of VEGFA. It also reduced the angiogenic-inhibitors, chemokine (C-X-C motif) ligand 10 (CXCL10) and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNAs, which were upregulated under hyperglycemia-hypoxia. In addition metformin, increased expression of STEAP family member 4 (STEAP4) under euglycemia, indicating an anti-inflammatory effect. CONCLUSIONS: Metformin has a dual effect by simultaneously increasing VEGFA and reducing CXCL10 and TIMP1 in CD34(+) cells in a model of the diabetic state combined with hypoxia. Therefore, these angiogenic inhibitors are promising therapeutic targets for CVD in diabetic patients. Moreover, our data are commensurate with a vascular protective effect of metformin and add to the understanding of underlying mechanisms.


Subject(s)
Angiogenesis Inducing Agents/pharmacology , Antigens, CD34/metabolism , Chemokine CXCL10/metabolism , Hyperglycemia/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Myocardial Infarction/drug therapy , Neovascularization, Physiologic/drug effects , Stem Cells/drug effects , Tissue Inhibitor of Metalloproteinase-1/metabolism , Vascular Endothelial Growth Factor A/metabolism , Biomarkers/metabolism , Cell Hypoxia , Cells, Cultured , Chemokine CXCL10/genetics , Dose-Response Relationship, Drug , Down-Regulation , Gene Expression Profiling , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/immunology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Hyperglycemia/genetics , Hyperglycemia/immunology , Hyperglycemia/metabolism , Hyperglycemia/physiopathology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Myocardial Infarction/immunology , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Oxidoreductases/genetics , Oxidoreductases/metabolism , Phenotype , Stem Cells/immunology , Stem Cells/metabolism , Tissue Inhibitor of Metalloproteinase-1/genetics , Up-Regulation , Vascular Endothelial Growth Factor A/genetics
4.
BMC Complement Altern Med ; 15: 193, 2015 Jun 23.
Article in English | MEDLINE | ID: mdl-26100532

ABSTRACT

BACKGROUND: Acute pancreatitis is an inflammatory disease caused by several factors such as viral infection, drugs, and diagnostic endoscopy. The aim of this study was to evaluate the potential protective or therapeutic effects of L-lysine on pancreatitis induced by L-arginine in mice. METHODS: Four groups of mice (10 in each group) were assessed. Group I was the control. Animals in groups II-IV were injected intraperitoneally with L-arginine hydrochloride (400 mg/kg body weight [bw]) for 3 days. Group III animals were orally pre-treated with L-lysine (10 mg/kg bw), whereas group IV animals were orally post-treated with L-lysine (10 mg/kg bw). Serum samples were subjected to amylase, lipase, transaminase, and interleukin-6 (IL-6) assays. The pancreas was excised to measure the levels of malondialdehyde, nitric oxide, catalase, superoxide dismutase, reduced glutathione, and glutathione peroxidase. RESULTS: Pre- or post-treatment with L-lysine led to significant decreases in the levels of malondialdehyde and nitric oxide, while significant enhancement was observed in the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and glutathione (p < 0.001). However, the treatment potential of L-lysine was better as a protective agent than a therapeutic agent. CONCLUSIONS: L-lysine treatment attenuates pancreatic tissue injury induced by L-arginine by inhibiting the release of the inflammatory cytokine IL-6 and enhance antioxidant activity. These effects may involve upregulation of anti-inflammatory factors and subsequent downregulation of IL6.


Subject(s)
Lysine , Pancreas , Pancreatitis , Acute Disease , Animals , Interleukin-6/metabolism , Lysine/pharmacology , Lysine/therapeutic use , Mice , Oxidative Stress/drug effects , Pancreas/chemistry , Pancreas/drug effects , Pancreas/enzymology , Pancreatitis/drug therapy , Pancreatitis/metabolism
5.
Toxicol Ind Health ; 31(4): 304-18, 2015 Apr.
Article in English | MEDLINE | ID: mdl-23315089

ABSTRACT

"Convolvulus hystrix Vahl" is a plant that has been known to Ancient Egyptians and to Arabs and its root was used traditionally as a purgative. Our attention was directed to the root bark as we observed that the largest part of the plant is deeply impeded underground. The work plan involved testing experimental animals for the influence of aqueous root bark extract on carbohydrate, fat and protein metabolisms as reflected on the growth and relevant laboratory metabolic assessment parameters. Proximate analysis showed high percentages of moisture (85%) and total lipids (7.2%) and surprising amounts of elements such as barium, strontium, rhodium and tellurium (1.7 mg, 3.1 mg, 8 mg and 9.1 mg/g ash, respectively). Random serum glucose value showed a significant decrease in the treated female group (p < 0.05). Serum total proteins of treated female group were found to be increased significantly (p < 0.001), while it was found to be decreased in the relevant treated male group (p < 0.01), together with a significant decrease in blood urea nitrogen (p < 0.05), with a significant increase in the serum creatinine (p < 0.05). Concerning serum fat metabolic parameters, a significant decrease in the serum triglycerides and high-density lipoproteins (p < 0.01 and p < 0.01, respectively) were found. We concluded that the presence of huge amount of polyphenolics such as tannins is responsible for the overall results documented as growth retarding and antinutritional factors. The results were motivating and pointed out to the possible opening of vast areas of research in the field of natural products. We recommend a series of biochemical and pharmacological studies concerning different parts of the plant as well.


Subject(s)
Body Weight/drug effects , Convolvulus/chemistry , Plant Extracts/chemistry , Plant Extracts/toxicity , Animals , Eating/drug effects , Female , Liver/drug effects , Liver/pathology , Male , Organ Size/drug effects , Plant Bark/chemistry , Rats , Rats, Wistar
6.
Molecules ; 20(8): 14425-34, 2015 Aug 07.
Article in English | MEDLINE | ID: mdl-26262605

ABSTRACT

Reactive oxygen species play a significant role in the pathogenesis of retinopathy in diabetes patients. The current study aimed to assess the effect of ethyl acetate extract (EAE) from Balanites aegyptiaca (10, 25 or 50 mg/kg b.w.) in experimental diabetic rats. To achieve this aim, five groups of male rats were included: control, diabetic, and diabetic rats treated with 10, 25, and 50 µg/kg b.w. of EAE for eight weeks. Our results suggests a protective role of EAE against oxidative stress induced by streptozocine. EAE treatment produced a reduction in blood glucose levels, HbA1c, malondialdehyde and vascular endothelial growth factor (VEGF) in diabetic retina (p < 0.001), as well as an enhancement in antioxidant capacity against streptozocine-induced oxidative stress. Tumor necrosis factor alpha (TNF-α), interleukin (IL-1ß) and vascular endothelial growth factor (VEGF) were significantly reduced in diabetic rats treated with EAE, compared with untreated diabetic rats. Analysis of EAE by GC-MS indicated the presence of ß-sistosterol. Overall, EAE modulates oxidative stress induced by streptozocine and enhances antioxidant activity, which may provide additional endothelial protection in retina of diabetic rats. These results hold great promise in the management of diabetic complications.


Subject(s)
Balanites/chemistry , Diabetes Mellitus, Experimental/drug therapy , Hyperglycemia/drug therapy , Plant Extracts/pharmacology , Acetates/chemistry , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/blood , Diabetic Retinopathy/blood , Diabetic Retinopathy/drug therapy , Disease Models, Animal , Dose-Response Relationship, Drug , Hyperglycemia/blood , Male , Oxidative Stress/drug effects , Plant Extracts/isolation & purification , Rats , Reactive Oxygen Species/metabolism
7.
Mol Biol Rep ; 41(1): 365-72, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24242674

ABSTRACT

The phylogenetic relationships of 60 accessions representing ten species of the genus Hordeum were investigated based on AFLP markers and seed storage protein SDS-PAGE electrophoresis. A total of 339 AFLP polymorphic markers were scored as a result of fingerprinting the studied taxa using seven AFLP primer combinations, whereas 46 polymorphic protein bands resulted from the water soluble and water non-soluble seed storage protein electrophoresis. The phylogenetic tree deduced from AFLP analysis is concordant in a large extent with that deduced from seed storage protein electrophoresis. The studied taxa were clustered according to their genome type into two main groups representing the Old and New World's species. Inside each group the species were clustered according to their genome type. Highly significant cophenetic correlation coefficient was obtained between both AFLP (0.96) and seed storage protein (0.89) indicating the reliability of the results.


Subject(s)
Hordeum/genetics , Polymorphism, Genetic , Seed Storage Proteins/metabolism , Amplified Fragment Length Polymorphism Analysis , Electrophoresis, Polyacrylamide Gel , Genes, Plant , Genetic Markers , Hordeum/metabolism , Molecular Typing , Phylogeny , Plant Leaves/genetics , Seed Storage Proteins/isolation & purification , Seeds/metabolism
8.
BMC Complement Altern Med ; 14: 282, 2014 Aug 03.
Article in English | MEDLINE | ID: mdl-25088145

ABSTRACT

BACKGROUND: Cisplatin (CP) is known as a potent anti-cancer drug. The most therapeutic adverse effect of CP is induced hepatotoxicity. In the present study, the protective effect of thymoquinone (TQ) on CP-induced hepatotoxicity was studied. METHODS: Wistar rats were divided into three groups (15 rats each). Group 1 served as the control group. Group 2 rats were injected ip with a single dose of CP (12 mg/kg b.w, i.p.). Group 3 rats were orally pre-treated with TQ (500 mg. kg(-1). day(-1)) for one month, then the animals were injected i.p with CP 12 mg.kg(-1). RESULTS: The beneficial effects of TQ with its antioxidant/anti-inflammatory effects were observed. Injection of rats with CP markedly affected the liver functions and histopathological changes. The antioxidant enzyme activities and reduced glutathione (GSH) contents were significantly decreased while the levels of malondialdehyde (MDA) significantly increased. The electromobility shift assay (EMSA) showed a significant activation of NF-κB-p65 in the rat liver injected with CP. Furthermore, the expression and concentrations of inflammatory tumor necrosis factor (TNF-α), nitric oxide synthetase (iNOS), and interleukin (IL-1ß) were markedly elevated in the CP injected rats. The administration of TQ improved all the altered functions, histopathology of the liver and attenuated the activated NF-κB. The antioxidant enzyme activities (glutathione peroxidase and glutathione -S transferase) of the rat livers were markedly increased while MDA was reduced as a result of TQ administration. In addition, the expression of TNF-α, iNOS, and IL-1ß were markedly reduced. CONCLUSION: It was concluded that, TQ has potential benefits in the prevention of the onset and progression of CP induced hepatotoxicity.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Benzoquinones/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Cisplatin/toxicity , Liver/drug effects , NF-kappa B/metabolism , Animals , Chemical and Drug Induced Liver Injury/etiology , Cytokines/metabolism , Drug Interactions , Liver/metabolism , Male , Oxidative Stress/drug effects , Random Allocation , Rats , Rats, Wistar , Signal Transduction/drug effects
9.
Toxicol Ind Health ; 30(6): 570-5, 2014 Jul.
Article in English | MEDLINE | ID: mdl-23024110

ABSTRACT

Cyclophosphamide (CP) is an alkylating agent that has been considered effective for cancer treatment. Lycopene, the pigment in tomato fruits, has beneficial effect in the treatment of some diseases. The goal of this study is to evaluate the protective effect of lycopene alone or combined with melatonin (Mel) in inhibiting the oxidative stress and toxic effect of CP in rats. Five groups of rats were included in this study; Group I served as the control. Rats in groups II-V were administrated with single dose of CP (150 mg/kg B.W) interperitoneally for 3 days. On the same day of CP administration, the rats in group III were fed a diet supplemented with lycopene (50 mg/kg of diet), rats in group IV were administered with a dose of 2.5 mg Mel/kg body weight (bw) injected subcutaneously and rats in group V were supplemented with lycopene and a dose of 2.5 mg Mel/kg bw injected subcutaneously. After 15 days the blood samples were collected. Results obtained showed that CP exerted its toxic effect by increasing the free radicals and reactive oxygen species that causes lipid peroxidation and cell damage, and this in turn is detected by elevation in nitric oxide (NO) and malondialdehyde (MDA), while the activities of antioxidants enzymes including (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) were significantly decreased as compared with the control rats. The combined treatment (Lyco + Mel) group showed potential reduction in these parameters more than those treated with lyco alone. The activities of SOD, CAT and GPx were found significantly high than lyco alone treated rats. A positive significant correlation between NO and MDA (r = .81). In conclusion, these results suggested that supplementation of diet with lycopene and Mel provided antioxidant defense with strong chemopreventive activity against Cp-induced cytotoxicity.


Subject(s)
Antineoplastic Agents, Alkylating/adverse effects , Carotenoids/pharmacology , Cyclophosphamide/adverse effects , Melatonin/pharmacology , Oxidative Stress/drug effects , Animals , Antineoplastic Agents, Alkylating/pharmacology , Carotenoids/administration & dosage , Catalase/blood , Cyclophosphamide/antagonists & inhibitors , Cyclophosphamide/pharmacology , Drug Synergism , Glutathione Peroxidase/blood , Lycopene , Male , Malondialdehyde/blood , Melatonin/administration & dosage , Nitric Oxide/blood , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/blood
10.
Toxicol Ind Health ; 29(2): 202-8, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22287617

ABSTRACT

Nicotine is a major pharmacologically active and addictive component of tobacco smoke, which is regarded to be a primary risk factor in the development of cardiovascular and pulmonary diseases. Epicatechin is one of the most potent antioxidants present in the human diet. Particularly high levels of this compound are found in tea, apples and chocolate. It has been reported that tea extracts and/or its constituents have antibacterial, antiviral, antioxidative, antitumor and antimutagenic activities. Vitamin E is a major lipid-soluble antioxidant vitamin and free radical scavenger, presents as an integral component of cellular membranes and has important biological functions. The primary mechanism by which vitamin E is proposed to prevent cancer is through their antioxidant properties. The goal of this study is to evaluate the effect of epicatechin alone or combined with vitamin E in inhibiting the oxidative stress induced by nicotine in rats. Results obtained indicated that there was a significant elevation in the levels of malondialdhyde (MDA) in nicotine injected rats. The combined treatment (epicatechin + Vit E) group showed a potential reduction of these parameters more than individual treatment. The activities of superoxide dismutase, catalase and glutathione peroxidase were found significantly higher in combined treated than untreated rats. In nicotine group, a negative significant correlation between reduced glutathione and MDA (r = -0.92) was observed. In conclusion, these results suggested that the supplementation of diet with epicatechin and vitamin E provided antioxidant defense with strong chemopreventive activity against nicotine-induced carcinogenesis.


Subject(s)
Antioxidants/pharmacology , Catechin/pharmacology , Nicotine/toxicity , Nicotinic Agonists/toxicity , Oxidative Stress/drug effects , Vitamin E/pharmacology , Animals , Drug Therapy, Combination , Glutathione/metabolism , Malondialdehyde/metabolism , Oxidoreductases/metabolism , Rats
11.
Toxicol Ind Health ; 28(6): 542-8, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22033431

ABSTRACT

Breast cancer is one of the most serious problems in oncology. We investigated the antitumor potential of lycopene (Lyco) alone or combined with tocopherol (Lyco + Toco) for 90 days against a single oral dose of (50 mg/kg body weight) 7,12-dimethyl[a]benzanthracene (DMBA)-induced oxidative stress and mammary carcinogenesis in female rats. The treatment protocol started from the day immediately after DMBA administration. Results obtained indicated that there was a significant elevation in the levels of malondialdehyde (MDA) and nitric oxide (NO) in serum and breast tissues of DMBA-injected rats. The combined treatment (Lyco + Toco) group showed a potential reduction of these parameters more than Lyco alone group. The activities of superoxide dismutase, catalase, and glutathione peroxidase were found to be significantly higher when compared to rats treated with Lyco alone. In DMBA group, a positive significant correlation between NO and MDA (r = 0.92) was observed. Histopathological examination revealed the formation of tumor and angiogenesis in DMBA-induced rats and these abnormal changes were ameliorated by combined treatment with Lyco + Toco. In conclusion, these results suggested that supplementation of diet with Lyco and Toco provided antioxidant defense, with strong chemopreventive activity against DMBA-induced mammary tumors.


Subject(s)
Antioxidants/pharmacology , Carotenoids/pharmacology , Mammary Neoplasms, Animal/drug therapy , Oxidative Stress/drug effects , Tocopherols/pharmacology , 9,10-Dimethyl-1,2-benzanthracene , Animals , Body Weight/drug effects , Catalase/metabolism , Drug Synergism , Female , Glutathione Peroxidase/metabolism , Lycopene , Malondialdehyde/blood , Mammary Neoplasms, Animal/chemically induced , Mammary Neoplasms, Animal/metabolism , Mammary Neoplasms, Animal/pathology , Nitric Oxide/blood , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Tocopherols/therapeutic use
12.
Toxicol Ind Health ; 28(5): 387-92, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22033426

ABSTRACT

Osteoporosis represents a major public health problem through its association with fragility fractures, primarily of the hip, spine and distal forearm. The risk of osteoporosis increased in postmenopausal women due to decline in estrogen levels. Replicable hormone therapy is associated with undesirable side effects. Cod liver oil (CLO) is a rich source of docosahexaenoic acid eicosapentaenoic acid linolenic acid and vitamins A, E and D. In this study, the effect of CLO will be tested in the prevention of bone loss in the ovariectomized (OVX) female rats. One group of OVX rats (n = 12) received an estrogen implantation at the time of operation and the second group was supplemented orally with CLO (200 µl/kg body weight) daily for 8 weeks. At the end of the experiment, blood was analysed for serum calcium, phosphorous, bone-specific alkaline phosphatase, osteocalcin and estrogen and femur for calcium determination. Estrogen implantation as well as CLO supplementation in OVX rats increased the calcium level in femur as compared with sham rats (p < 0.05). It is concluded that supplementation of CLO have a positive effect on bone mineralization in rat, and this could offer a new strategy to avoid the side effects of replaceable hormonal therapy.


Subject(s)
Calcification, Physiologic/drug effects , Cod Liver Oil/pharmacology , Ovary/physiology , Analysis of Variance , Animals , Diet , Estrogens/blood , Estrogens/pharmacology , Fatty Acids, Essential/blood , Female , Femur/chemistry , Osteocalcin/blood , Ovariectomy , Rats , Rats, Sprague-Dawley
13.
Arch Physiol Biochem ; 128(1): 32-36, 2022 Feb.
Article in English | MEDLINE | ID: mdl-31507207

ABSTRACT

The rational of this study to find out the impact of auxins in prevention of diabetic complications in rats. Seventy-five rats were randomly grouped into five groups: Group I; control (n = 15). (Groups 2-5, 60 rats) were received a single dose of STZ i.p, at dose of 65 mg/kg for induction diabetes. Group II; diabetic untreated. Group III; Rats were given auxin subcutaneous (2.5 µg/kg b.w). Group IV; rats were given auxin (5 µg/kg b.w). Group V; rats were injected insulin (5 units/kg b.w/day) as positive control. Treatment of diabetic rats with auxin (2.5 or 5 ug/kg b.w) for 8 weeks reversed the oxidant/antioxidant imbalance. The protective effect of auxin due to defence against oxygen free radicals production in retinal tissue. Also, auxin inhibit formation of AGEs and inhibit release of inflammatory mediators. It was concluded that, auxin may be used as promising therapeutic agents against diabetic complications.


Subject(s)
Diabetes Mellitus, Experimental , Insulin Resistance , Animals , Antioxidants/pharmacology , Blood Glucose , Diabetes Mellitus, Experimental/drug therapy , Indoleacetic Acids , Insulin , Rats
14.
Environ Sci Pollut Res Int ; 29(19): 28743-28748, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34988825

ABSTRACT

Nowadays, phthalates widely employed in many products are distributed around us which contributed to the development of many chronic diseases. We investigated the incidence of type 2 diabetes mellitus (T2DM) in Saudi subjects and correlated it with urinary phthalate metabolites' screening study.We selected a total of 100 cases early diagnosed as type 2 diabetes mellitus (FBS ≥ 126 mg/dl, PP 2 h, ≥ 140 mg/dl) and 50 normal subjects (FBS ≤ 90 mg/dl) as control. Overnight fasting blood samples were subjected for assay of FBS, glycated hemoglobin, insulin, C-peptide, HOMA-IR, advanced glycation end products (AGEs), and urinary assay of some phthalate metabolite levels.Data obtained showed a significant elevation of FBS, HA1c, AGEs, insulin, and C-peptide and HOMA-IR in diabetic patients compared with the control (p < 0.001). Urinary phthalate metabolites such as mono-ethyl phthalate (mEP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and mono-n-butyl phthalate (mBP) were detected in significant concentrations in diabetic patients compared with control. A positive correlation was found between mEP and mBP and HOMA-IR and C-peptide.Phthalate toxicity is considered as one of the risk factors that contributed to insulin resistance and development of T2DM via increasing the levels of HOMA-IR and C-peptide.This will result in the risk of phthalate exposure for diabetogensis and its economic cost for treatment lifetime.


Subject(s)
Diabetes Mellitus, Type 2 , Environmental Pollutants , Phthalic Acids , C-Peptide , Diabetes Mellitus, Type 2/epidemiology , Environmental Exposure/analysis , Environmental Pollutants/metabolism , Humans , Incidence , Insulin , Phthalic Acids/metabolism , Saudi Arabia/epidemiology
15.
Oncol Lett ; 22(1): 508, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33986869

ABSTRACT

Long non-coding RNAs (lncRNAs), a type of cellular RNA, play a critical regulatory role in several physiological developments and pathological processes, such as tumorigenesis and tumor progression. Obesity is a risk factor for a number of serious health conditions, including breast cancer (BC). However, the underlying mechanisms behind the association between obesity and increased BC incidence and mortality remain unclear. Several studies have reported changes in lncRNA expression due to obesity and BC, independently encouraging further investigation of the relationship between the two in connection with lncRNAs. The present study was designed to first screen for the expression of 29 selected lncRNAs that showed a link to cancer or obesity in the blood of a selected cohort of 6 obese and 6 non-obese patients with BC. The expression levels of significantly expressed lncRNAs, AP001429.1, PCAT6, P5549, P19461 and P3134, were further investigated in a larger cohort of 69 patients with BC (36 obese and 33 non-obese), using reverse transcription-quantitative polymerase chain reaction. Results showed not only that AP001429.1 remained significantly downregulated in the larger cohort (P=0.002), but also that it was associated with several clinicopathological characteristics, such as negative HER2 status, negative E-cadherin expression, negative vascular invasion, negative margin invasion and LCIS. These findings suggest that obesity may have a role in inhibiting AP001429.1 expression, which may serve as a novel potential biomarker and therapeutic target for BC.

16.
J Biomol Struct Dyn ; 39(11): 4175-4184, 2021 07.
Article in English | MEDLINE | ID: mdl-32475223

ABSTRACT

SARS coronavirus (COVID-19) is a real health challenge of the 21st century for scientists, health workers, politicians, and all humans that has severe cause epidemic worldwide. The virus exerts its pathogenic activity through by mechanism and gains the entry via spike proteins (S) and Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins on host cells. The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp). Docking studies were designed in order to obtain the binding energies for Plantaricin metabolites. The binding energies for Plantaricin W were -14.64, -11.1 and -12.68 for polymerase, RBD and ACE2 respectively comparatively very high with other compounds. Plantaricin W, D, and JLA-9 were able to block the residues (THR556, ALA558) surrounding the deep grove catalytic site (VAL557) of RdRp making them more therapeutically active for COVID-19. Molecular dynamics studies further strengthen stability of the complexes of plantaricin w and SARS-CoV-2 RdRp enzyme, RBD of spike protein, and human ACE2 receptor. The present study present multi-way options either by blocking RBD on S proteins or interaction of S protein with ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by Plantaricin molecules paving a way that can be useful in the treatment of COVID-19 until some better option will be available.Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , Probiotics , Antiviral Agents/pharmacology , Humans , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
17.
Biomed Pharmacother ; 142: 111960, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34352718

ABSTRACT

Hepatocellular carcinoma is one of the most common causes of cancer-related deaths globally. Bioavailable, effective and safe therapeutic agents are urgently needed for cancer treatment. This study evaluated the metabolomics profiling, anti-proliferative and pro-apoptotic effects of strigol/albumin/chitosan nanoparticles (S/A/CNP) on HepG2 cell line. The diameter of S/A/CNP was (5 ±â€¯0.01) nm. The IC50 was 180.4 nM and 47.6 nM for Strigol1 and S/A/CNP, respectively, after incubation for 24 h with HepG2 cells. By increasing the concentration of S/A/CNP, there was chromatin condensation, degranulation in the cytoplasm and shrinking in cell size indicating pro-apoptotic activity. Metabolomics profiling of the exposed cells by LC/MS/MS revealed that S/A/CNP up-regulated epigenetic intermediates (spermine and spermidine) and down-regulated energy production pathway and significantly decreased glutamine (P < 0.001). These findings demonstrated that S/A/CNP has anti-proliferative, apoptotic effects and modulate energetic, and epigenetic metabolites in the hepatocellular carcinoma cell line (HepG2).


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Lactones/pharmacology , Liver Neoplasms/drug therapy , Nanoparticles , Apoptosis/drug effects , Carcinoma, Hepatocellular/genetics , Cell Proliferation/drug effects , Cell Survival/drug effects , Chitosan/chemistry , Chromatography, Liquid , Down-Regulation/drug effects , Hep G2 Cells , Humans , Inhibitory Concentration 50 , Lactones/administration & dosage , Liver Neoplasms/genetics , Metabolomics , Particle Size , Serum Albumin, Human/chemistry , Tandem Mass Spectrometry , Up-Regulation/drug effects
18.
Afr Health Sci ; 21(3): 1451-1459, 2021 Sep.
Article in English | MEDLINE | ID: mdl-35222610

ABSTRACT

BACKGROUND: The metabolic pathways can be affected by dysregulation in thyroid hormone levels which in turn can arise from environmental chemical exposure. This study investigated the association of selected trace elements with thyroid disorders in a Saudi population. METHODS: Urine samples collected from 100 participants (50 thyroid disorder patients and 50 controls) were analyzed to determine trace elements using inductively coupled plasma-mass spectrometer. Non-parametric Mann-Whitney Test, were used to examine the association between socio-demographic as well as clinical characteristics of thyroid profile levels (T3, T4 and TSH) and urinary trace element concentrations. RESULTS: Urine from patients with thyroid disorders had significantly higher concentrations of Ni, Cu, and Cd (p-values <0.0005). In contrast, urinary Cr and Zn (p-values <0.013 and 0.005) were low in thyroid patients compared to the control. CONCLUSION: First study to report urinary trace element levels showed a possible link between thyroid disorders and trace element exposure which reflect the environmental pollution..


Subject(s)
Metals, Heavy , Thyroid Diseases , Trace Elements , Environmental Exposure , Environmental Monitoring , Humans , Metals, Heavy/analysis , Thyroid Hormones , Trace Elements/analysis
19.
Saudi J Biol Sci ; 27(3): 894-898, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32127768

ABSTRACT

This study investigated the in vitro antioxidant, proapoptotic and anti-proliferative activity of phycocyanin extracted from Ulva lactuca (Chlorophyta) algae extract loaded on albumin nanoparticle (ULANP). The characterization of ULANP profile was done by using FTIR and its cytotoxicity was investigated by using MTT assay against HepG2 and MCF7 cell lines. The proapoptotic markers caspase 8 & 9 were measured. Analysis of ULANP by FTIR showed the characteristic band (2100 cm-1 ~3700 cm-1) that is indicated primarily by -COO, -CO and conjugated double bond. These bonds showed the spectral band at peaks of 2985 cm-1 and 2860 cm-1, 2986 cm-1 respectively. The antioxidant potential and radical scavenging property of ULANP was also appreciable as compared to the vitamin C and gallic acid. The antiproliferative assay carried out by WST-1 suggests that ULANP was effective against both HepG2 (93.17%) and MCF7 (91.3%). Caspase-8 and -9 were significantly elevated (p < 0.001) in both the cell lines of breast and liver cancer. It was concluded that ULANP induced anti-proliferative and pro-apoptotic activities on liver and breast cancer. It is promising as a novel antitumor activity for further investigation the mechanistic pathways mediated this action.

20.
Arch Med Res ; 51(2): 145-152, 2020 02.
Article in English | MEDLINE | ID: mdl-32111499

ABSTRACT

BACKGROUND: The role of Notch signaling dysregulation in causing metastatic breast cancer is not yet elucidated, therefore, this study aimed to investigate the expression of DLL4 and JAG1 in metastatic breast cancer. Moreover, we examined the possible association between clinicopathological features and studied parameters. DESIGN AND METHODS: A total of 90 patients with invasive ductal breast carcinomas (52 non-metastatic and 38 metastatic) were enrolled in the current study. Furthermore, there were 42 patients with benign breast diseases. The mRNA and protein expression of DLL4 and JAG1 were analyzed by RT-PCR and ELISA, respectively in breast cell lysates. RESULTS: The mRNA and protein expression of DLL4 and JAG1 were obviously higher in patients with breast cancer compared to patients with benign breast diseases and in metastatic versus non-metastatic breast cancer. A significant positive correlation was declared between DLL4 and JAG1 at both mRNA and protein levels in metastatic and localized breast cancer patients. Highly expressed mRNA and protein of DLL4 and JAG1 were associated with late tumor stages; moreover, upregulation of mRNA and protein of JAG1 was correlated with poorly differentiated tumors. CONCLUSION: Our data emphasize that overexpression of DLL4 and JAG1 could predict the development of distant metastasis in breast cancer patients.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Breast Neoplasms/genetics , Calcium-Binding Proteins/metabolism , Jagged-1 Protein/metabolism , Neoplasm Metastasis/genetics , Breast Neoplasms/pathology , Female , Humans , Incidence , Jagged-1 Protein/genetics , Middle Aged
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