Pathological Characters and Molecular Pathogenesis of Diabetic Neuropathic Osteoarthropathy Cartilages Damage

Abstract Background: Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods: The articular cartilages of 8 patients with DNOAP and 8 normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage, and the ultrastructural changes of chondrocytes were detected by electron microscopy. Chondrocyte were isolated from DNOAP group and control group. The expression of RANKL, OPG, IL-1β, IL-6, TNF-α, Aggrecan protein were evaluated by Western blot. ROS levels were measured using a DCFH-DA probe. The percentage of apoptotic cells was determined by flow cytometry. The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG.Results: Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swelling were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 VS 11.9 ± 0.7, P < 0.05). The expression of RANKL, TNF-α, IL-1β and IL-6 protein in DNOAP group was higher than that in normal control group, while OPG and Aggrecan protein was lower than that in normal control group (both P < 0.05). Flow cytometry showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (P < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15mM.Conclusions: DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL, OPG) and inflammatory cytokines (IL-1β, IL-6 and TNF-α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15mM made the RANKL / OPG ratio changed rapidly.

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Pathological Characters and Molecular Pathogenesis of Diabetic Neuropathic Osteoarthropathy Cartilages Damage

Foot & Ankle Orthopaedics ◽

10.1177/2473011420s00255 ◽

2020 ◽

Vol 5 (4) ◽

pp. 2473011420S0025

Author(s):

Zhao Hong-Mou

Keyword(s):

Electron Microscopy ◽

Flow Cytometry ◽

Normal Control ◽

Subchondral Bone ◽

Normal Control Group ◽

Molecular Pathogenesis ◽

Control Group ◽

Relative Expression ◽

Diabetic Neuropathic Osteoarthropathy ◽

Neuropathic Osteoarthropathy

Category: Basic Sciences/Biologics Introduction/Purpose: The aim of current study was to investigate the pathological characters and relative molecular pathogenesis of the cartilages damage in diabetic neuropathic osteoarthropathy (DNOAP) patients. Methods: The articular cartilages of ankle joint, subtalar joint and talonavicular joint of 8 patients with DNOAP from March 2017 to June 2018 were selected as DNOAP group. And the articular cartilage of matched joints from 8 amputation patients were selected as control group. Masson staining and safranine O/fixed green staining were used to observe the histopathological characteristics of cartilage, and the ultrastructural changes of chondrocytes were observed by electron microscopy. Chondrocyte culture was carried out in DNOAP group and control group. Western blot was used to detect the expression of RANKL, OPG, IL-1ß, IL-6, TNF-a, Aggrecan protein in chondrocyte. DCFH-DA probe was used to detect the level of reactive oxygen species in chondrocyte. Flow cytometry was used to detect the apoptotic rate of chondrocyte. Results: In DNOAP group, chondrocytes decreased, subchondral bone proliferated, structure disordered and osteoclasts formed in a large number in subchondral bone area. Under transmission electron microscopy, mitochondrial and endoplasmic reticulum swelling were observed in DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1±2.3 VS 11.9±0.7, P<0.05). The relative expression of RANKL, TNF-a, IL-1ß and IL-6 protein in DNOAP group was higher than that in normal control group, while the relative expression of OPG and Aggrecan protein was lower than that in normal control group (both P < 0.05). Flow cytometry showed that the apoptotic rate of chondrocyte in DNOAP group was 3.3%±0.2%, which was higher than that in normal control group (1.2%±0.1%, P<0.05). Conclusion: Serious destruction of chondrocytes and organelles structure was the pathological characteristics of DNOAP. Inflammation plays a role in promoting the pathogenesis of DNOAP.

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Lactobacillus rhamnosus confers protection against colorectal cancer in rats

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i7.12 ◽

2021 ◽

Vol 18 (7) ◽

pp. 1449-1454

Author(s):

Jian Huang ◽

Dan Wang ◽

Anye Zhang ◽

Qinglian Zhong ◽

Qun Huang

Keyword(s):

Colorectal Cancer ◽

Treatment Group ◽

Normal Control ◽

Quantitative Polymerase Chain Reaction ◽

Lactobacillus Rhamnosus ◽

Normal Control Group ◽

Control Group ◽

Ether Anesthesia ◽

Tnf Α ◽

Factor Α

Purpose: To investigate the protective effect and mechanism of action of Lactobacillus rhamnosus against colorectal cancer (CRC). Methods: A total of 40 healthy female Sprague Dawley rats weighing 100 – 140 g (mean weight = 120 ± 20 g) were used for this study. The rats were randomly assigned to four groups of 10 rats each: normal control group, L. rhamnosus group; 1, 2-dimethylhydrazine (DMH) group and treatment group. Rats in L. rhamnosus group were inoculated with L. rhamnosus (1 x 108 CFU/mL) orally for 20 weeks, while rats in DMH group received 35 mg DMH/kg /week intraperitoneally for 10 weeks for induction of CRC. Treatment group rats received 35 mg DMH/kg bwt intraperitoneally for 10 weeks for induction of CRC, and were treated with L. rhamnosus (1 x 108 CFU/mL) orally for 20 weeks. After 20 weeks, the rats were euthanized using ether anesthesia. Expressions of inflammatory, angiogenesis and proapoptotic genes were determined using Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: Treatment with L. rhamnosus significantly reduced the incidence of CRC in the rats (p < 0.05). The incidence of multiple tumors in the treatment group was also significantly reduced, when compared to DMH group (p < 0.05). The protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), cyclooxygenase-2 (COX-2), bcl-2 and vascular endothelial growth factor α (VEGF-α) were significantly upregulated in DMH group, when compared with normal control group (p < 0.05). However, treatment with L. rhamnosus significantly down-regulated the expressions of these proteins (p < 0.05). DMH treatment also significantly upregulated the expressions of iNOS, TNF-α, VEGF-α, NF-kB, β-catenin and bax genes (p < 0.05). However, L. rhamnosus significantly reversed the effects of DMH on the expression levels of these genes (p < 0.05). Conclusion: These results show that L. rhamnosus prevents CRC via suppression of expressions of inflammatory and angiogenesis genes, and upregulation of apoptotic gene expression.

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Boeravinone B promotes fracture healing in ovariectomyinduced osteoporotic rats via the regulation of NF-κB p65/IκB-α/SIRT-1 signaling pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i5.7 ◽

2021 ◽

Vol 18 (5) ◽

pp. 955-960

Author(s):

Jianlin Zhang ◽

Longze Zong ◽

Dongyu Bai

Keyword(s):

Fracture Healing ◽

Signaling Pathway ◽

Normal Control ◽

Bone Mineral ◽

Normal Control Group ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Type I ◽

Expression Levels ◽

Tnf Α

Purpose: To investigate the fracture-healing effect of boeravinone B in ovariectomy-induced (OVX) osteoporotic rats. Methods: Adult female Wistar rats (n = 30) were ovariectomized and after three months, the unilateral cross-tibial fractures were fixed with intramedullary nails. The rats were then randomly assigned to three groups of 10 rats each: normal control group, OVX group and 100 mg/kg body weight boeravinone B group. Boeravinone B was orally administered for a period of 5 weeks. The effect of boeravinone B on indices of bone formation and resorption was assessed. Levels of inflammatory cytokines including tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1β) were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine the expression levels of NF-κB p65, IкB-α and SIRT1 proteins. Results: There were significant increases in the activities of tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP), and collagen type I fragment (CTX) level and serum osteocalcin (OC) of OVX group, when compared with normal control group (p < 0.05). However, treatment with boeravinone B significantly reduced the activities and levels of these parameters, relative to OVX group (p < 0.05). The levels of TNF-α and IL-1β significantly increased in OVX group, relative normal control group, but were significantly lower following treatment with boeravinone B (p < 0.05). Bone mineral content (BMC) was not significantly altered in OVX and boeravinone B-treated groups, when compared with normal control group (p > 0.05). There was significant reduction in bone mineral density (BMD) of OVX group relative to normal control group (p < 0.05). However, treatment with boeravinone B significantly increased the BMD, when compared with OVX group (p < 0.05). After Week 5 of treatment, boeravinone B significantly enhanced bone remodeling and formation of callus. Treatment with boeravinone B significantly reduced the expression levels of NF-κB p65 and IκB-α proteins, and significantly upregulated the expression of SIRT-1 (p < 0.05). Conclusion: The results obtained in this study suggest that boeravinone B promotes the healing of fracture caused by osteoporosis via a mechanism involving NF-κB p65/IκB-α/SIRT-1 signaling pathway.

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Change of Peripheral Blood Treg/Thl7 in Cognitive Impairment with Chronic Renal Failure Patients

Cellular Physiology and Biochemistry ◽

10.1159/000486809 ◽

2018 ◽

Vol 45 (1) ◽

pp. 281-290 ◽

Cited By ~ 2

Author(s):

Jie Wang ◽

Xue-Bin Li ◽

Peng Huang ◽

Mei-Ying Huang ◽

Xian-Jun Gu

Keyword(s):

Flow Cytometry ◽

Cognitive Impairment ◽

Cognitive Function ◽

Normal Control ◽

Peripheral Blood ◽

Th17 Cell ◽

Th17 Cells ◽

Normal Control Group ◽

Control Group ◽

Normal Cognitive Function

Background/Aims: To investigate the changes in peripheral blood Treg/Th17 cell balance and its significance in patients with chronic renal failure (CRF) and cognitive impairment. Methods: A total of 71 patients with CRF were enrolled as a study group. The patients were divided into a cognitive impairment group and a normal cognitive function group according to the Mini-Mental State Examination (MMSE). Peripheral blood Treg and Th17 cells were analyzed by flow cytometry and their relevant cytokines (IL-17, IL-10 and TGF-β) and other biochemical indicators, including C-reactive protein (CRP) and IL-6, were determined by ELISA. Results: Thepatients with both CRF and cognitive impairment were older than the cognitive normal groups. Peripheral blood Treg cells by Flow cytometry (the CRF cognitive impairment group 5.57±1.3%, CRF group with normal cognitive function 7.5 ± 0.9% and normal control group 9.7 ± 1.7%,P<0.05) and its related cytokines (IL-10 and TGF-β) by ELISA detection were lower in the group with cognitive impairment than in the group without cognitive impairment ( IL-10, 7.4±4.2 pg/mL, 13.8±3.9 pg/mL, 18.3±3.2 pg/mL; TGF-β 335.6±175.3 pg/mL, 512.7 ± 114.6 pg/mL, 953.8±373.4 pg/mL P < 0.05, respectively).However, Th17 cell numbers (the CRF cognitive impairment group 3.3 ± 0.7%, CRF group with normal cognitive function2.2 ± 0.5% and normal control group 1.5 ± 0.3%),and cytokine levels (IL-17, IL-6 and CRP) were higher in the group with cognitive impairment IL-6 (21.3 ± 5.1 pg/mL), IL-17 (18.5 ± 4.2 pg/mL) and CRP (20.3 ± 5.9 mg/L) in the CRF group with cognitive impairment when compared with the CRF group and normal cognitive function (12.2 ± 4.5 pg/mL, 12.1 ± 3.7 pg/mL and 13.5 ± 4.6 mg/L, respectively) or the normal control group (9.2 ± 5.8 pg/mL, 7.4 ± 2.6 pg/mL and 3.2 ± 1.3 mg/L, respectively, P<0.05). The frequencies of Treg in patients with CRF were positively correlated with the MMSE scores ((r = 0.518, P < 0.05), but the Th17 numbers were negatively correlated (r = -0.435, P < 0.05). Conclusion: An imbalance of peripheral blood Treg/Th17 cells is associated with cognitive impairment in patients with CRF.

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Study on potential differentially expressed genes in stroke by bioinformatics analysis

Neurological Sciences ◽

10.1007/s10072-021-05470-1 ◽

2021 ◽

Author(s):

Xitong Yang ◽

Pengyu Wang ◽

Shanquan Yan ◽

Guangming Wang

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Normal Control ◽

Enrichment Analysis ◽

Normal Control Group ◽

Control Group ◽

Ppi Network ◽

Hub Genes ◽

Pathway Enrichment ◽

Key Genes

AbstractStroke is a sudden cerebrovascular circulatory disorder with high morbidity, disability, mortality, and recurrence rate, but its pathogenesis and key genes are still unclear. In this study, bioinformatics was used to deeply analyze the pathogenesis of stroke and related key genes, so as to study the potential pathogenesis of stroke and provide guidance for clinical treatment. Gene Expression profiles of GSE58294 and GSE16561 were obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IS and normal control group. The different expression genes (DEGs) between IS and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA), the function and pathway enrichment analysis of DEGS were performed. Then, a protein–protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. A total of 85 DEGs were screened out in this study, including 65 upward genes and 20 downward genes. In addition, 3 KEGG pathways, cytokine − cytokine receptor interaction, hematopoietic cell lineage, B cell receptor signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the PPI network and CytoHubba, 10 hub genes including CEACAM8, CD19, MMP9, ARG1, CKAP4, CCR7, MGAM, CD79A, CD79B, and CLEC4D were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including hsa-mir-146a-5p, hsa-mir-7-5p, hsa-mir-335-5p, and hsa-mir-27a- 3p, were predicted as possibly the key miRNAs. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of ischemic stroke, and provide a new strategy for clinical therapy.

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Effect of GDM on the Expression of MT1-MMP and u-PA in Glioma Cells

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.1033-1034.220 ◽

2014 ◽

Vol 1033-1034 ◽

pp. 220-223

Author(s):

Xue Mei Han ◽

Li Bo Wang ◽

Ni Ni Li ◽

Song Yan Liu

Keyword(s):

Normal Control ◽

Glioma Cell ◽

Fetal Bovine Serum ◽

Glioma Cells ◽

Normal Control Group ◽

Control Group ◽

Rt Pcr ◽

Glioma Cell Lines ◽

Fetal Bovine ◽

Identify Gene Expression

To examine the effect of GDM on the expression of MT1-MMP and u-PA genes in glioma cells. Glioma cell lines U251 and U87 were cultured in DMEM medium supplemented with 10% fetal bovine serum. RT-PCR was used to identify gene expression level. The level of u-PA mRNA was up-regulated significantly in the HGF group compared with the normal control group (P<0.05). The expression of MT1-MMP and u-PA was significantly lower in the GDM group than in the normal control and HGF groups (P<0.05). The expression of u-PA in the HGF+GDM group was down-regulated significantly compared with the normal control and HGF groups (P<0.05).GDM can inhibit expression of both MT1-MMP and u-PA in glioma cells.

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Identification of Hub Genes Associated with Development of Lung Adenocarcinoma by Integrated Bioinformatics Analysis

10.21203/rs.3.rs-550498/v1 ◽

2021 ◽

Author(s):

Jinglei Li ◽

Wei Hou

Keyword(s):

Gene Expression ◽

Survival Analysis ◽

Network Analysis ◽

Lung Adenocarcinoma ◽

Normal Control ◽

Gene Expression Analysis ◽

Normal Control Group ◽

Control Group ◽

Differential Gene Expression Analysis ◽

Differential Gene

Abstract Purpose: Lung adenocarcinoma (LUAD) has high heterogeneity and poor prognosis, posing a major challenge to human health worldwide. Therefore, it is necessary to improve our understanding of the molecular mechanism of LUAD in order to be able to better predict its prognosis and develop new therapeutic strategies for target genes.Methods: The Cancer Genome Atlas and Gene Expression Omnibus, were selected to comprehensively analyze and explore the differences between LUAD tumors and adjacent normal tissues. Critical gene information was obtained through weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and survival analysis.Results: Using WGCNA and differential gene expression analysis, 29 differentially expressed genes were screened. The functional annotation analysis showed these genes to be mainly concentrated in heart trabecula formation, regulation of inflammatory response, collagen-containing extracellular matrix, and metalloendopeptidase inhibitor activity. Also, in the protein–protein interaction network analysis, 10 central genes were identified using Cytoscape's CytoHubba plug-in. The expression of CDH5, TEK, TIMP3, EDNRB, EPAS1, MYL9, SPARCL1, KLF4, and TGFBR3 in LUAD tissue was found to be lower than that in the normal control group, while the expression of MMP1 in LUAD tissue was higher than that in the normal control group. According to survival analysis, the low expression of MYL9 and SPARCL1 was correlated with poor overall survival in patients with LUAD. Finally, through the verification of the Oncomine database, it was found that the expression levels of MYL9 and SPARCL1 were consistent with the mRNA levels in LUAD samples, and both were downregulated.Conclusion: Two survival-related genes, MYL9 and SPARCL1, were determined to be highly correlated with the development of LUAD. Both may play an essential role in the development LUAD and may be potential biomarkers for its diagnosis and treatment in the future.

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FUNCTIONAL ANALYSIS OF AGERATUM CONYZOIDES L. (BABANDOTAN) LEAVES EXTRACT ON RHEUMATOID ARTHRITIS MODEL RAT

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i3.16428 ◽

2017 ◽

Vol 10 (3) ◽

pp. 429

Author(s):

Erna Harfiani ◽

Riri Nurul Suci ◽

Ade Arsianti ◽

Anton Bahtiar ◽

Katrin Basah

Keyword(s):

Rheumatoid Arthritis ◽

Normal Control ◽

Rat Model ◽

Control Group ◽

Paw Edema ◽

Ageratum Conyzoides ◽

Tnf Α ◽

Freund’S Adjuvant ◽

Complete Freund's Adjuvant ◽

Freund's Adjuvant

ABSTRACTObjective: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints. Ageratum conyzoides L. (Babandotan)leaves are proven to be used in inflammation therapy, yet there is a little data regarding the effects of the leaves on RA. The aim of this study is toinvestigate anti-RA activity of the ethanolic extract of A. conyzoides L. leaves (EEAL) harvested from Bogor, Indonesia, in rats.Methods: The phytochemical screening analysis and thin-layer chromatography were performed to analyze the constituents of the EEAL. This studyused white male Sprague Dawley rats which were divided into 6 groups; normal control and negative control groups, both given 0.5% carboxymethylcellulose; the positive control group, given methotrexate suspension (0.05 mg/200 g bw.); the dose variation extract is 40 mg, 80 mg, and 160 mg/200 gbody weight. All the groups were induced with 0.1 ml Complete Freund’s adjuvant on day 1, except normal control group. Some parameters will bemeasured, such as paw edema, levels of leukocyte and lymphocyte, concentrations of tumor necrosis factor-α (TNF-α), and the number of osteoclastsper mm2.Results: For 21 days the rats have given treated the EEAL in three doses, was showed the decreasing volume of paw edema, levels of blood leukocytesand lymphocytes, concentrations of TNF-α and the number of osteoclasts, compared to the rat model of RA.Conclusion: This study showed that the leaves of A. conyzoides L. harvested from Bogor, Indonesia, have activity as anti-RA in a rat model, in whichflavonoid plays a role in inhibition of chronic inflammatory processes.Keywords: Ageratum conyzoides L. leaves, Anti-rheumatoid arthritis, Complete Freund’s adjuvant, Flavonoids.

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Hepatotoxicity and Histological Evaluation of Aqueous and Methanolic Leaf Extracts of Thaumatococcus Daniellii and Alchornea Cordifolia in Wistar Rat Models

Modern Health Science ◽

10.30560/mhs.v1n2p42 ◽

2019 ◽

Vol 1 (2) ◽

pp. p42

Author(s):

Service @ Ideasspread.org ◽

Okafor I. J. ◽

Nweke E. O. ◽

Ewa O.

Keyword(s):

Normal Control ◽

Wistar Rat ◽

Normal Control Group ◽

Histological Evaluation ◽

Control Group ◽

Significant Elevation ◽

Leaf Extracts ◽

Group Iii ◽

Methanolic Extracts ◽

Group I

This study was carried out to ascertain the hepatotoxic potential of T.daniellii (T.d) and A. cordifolia (A.c). Investigations were conducted using standard methods. Oral administration of 200mg/kg aqueous leaf extracts of T.daniellii caused a non-significant increase in the activity of ALT (5.43±0.60IU/L), AST (16.93±0.26 IU/L) and ALP (160.70±1.04 IU/L) compared to the values recorded on the normal control (group I) ALT (3.84±0.16 IU/L), AST (14.19±0.52 IU/L) and ALP (157.26±0.64 IU/L). Group III administered with 200mg/kg methanolic leaf extract of T. daniellii manifested a significant elevation in the activity of ALT (13.15±0.89 IU/L), AST (22.84±0.38 IU/L) and ALP (170.40±0.44 IU/L) compared to the normal control. Similarly, groups IV and V which were orally administered with 200mg/kg aqueous and methanolic leaf extracts of A. cordifolia showed significant increase in the activity of ALT (6.32±0.33U/L), AST (17.70±0.030U/L) and ALP (161.13±0.09U/L) and ALT (7.55±0.59U/L), AST (19.35±0.26U/L) and ALP (165.38±0.35U/L) respectively compared to the values recorded on the control (group I). In conclusion, drug development protocols involving T. daniellii leaf should preferably use water as an ideal solvent. On the other hand, the hepatotocity associated with both aqueous and methanolic extracts of A. cordifolia could imply the presence of hepatotoxins in the leaf of the said plant.

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ACUTE TOXICOLOGICAL INVESTIGATION OF POLYETHYLENE GLYCOL DERIVATIZED FOURTH AND FIFTH GENERATION POLY (PROPYLENEIMINE) DENDRIMERS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i5.34203 ◽

2019 ◽

pp. 222-229 ◽

Cited By ~ 3

Author(s):

NITIN DWIVEDI ◽

DUSHYANT KUMAR PARMAR ◽

PRASHANT KESHARWANI ◽

JIGNA SHAH

Keyword(s):

Polyethylene Glycol ◽

Normal Control ◽

Normal Control Group ◽

Control Group ◽

Severe Toxicity ◽

Hemoglobin Content ◽

Dose Administration ◽

Fifth Generation ◽

Wbc Count ◽

Rbc Count

Objective: The aim of the present study leads a comparative assessment of the toxicological profile of PEGylated fourth and fifth-generation poly (propylene imine) dendrimers (PPI). Methods: 4.0G and 5.0G generations of PPI dendrimer were synthesized and PEGylated with Mono polyethylene glycol 5000 (MPEG-5000). Each PEGylated 4.0G and 5.0G dendrimeric generation were administered in three different doses: 2.5 mg/kg, 25 mg/kg and 250 mg/kg (i.e., low, intermediate and high dose) to wister rats. After the dose administration, the blood and tissue samples of wister rats were collected after 24 h and 15 d after. All the collected samples were proceeded for hematological, biochemical and histopathological studies. Results: After 24 h of (250 mg/kg) dose administration PEGylated 5.0G PPI dendrimer the RBC count, hemoglobin content and WBC count were found 7.873±0.129 mill/cmm, 13.833±0.491g/dl and 9033.33±2384.906 mill/cmm, while PEGylated 4.0G PPI dendrimer indicated RBC count, hemoglobin content and WBC count 8.733±0.239 mill/cmm, 14.033±0.12 g/dl and 9666.667±2567.316 mill/cmm, in blood samples as compare to RBC count 9.346±0.037 mill/cmm, hemoglobin content 15.35±0.15 g/dl and WBC count 8500±286.675 mill/cmm of the animals of normal control group. Thus there are no remarkable changes (p>0.05) in RBC count, hemoglobin content and other hematological profile after 24 h in comparison of normal control group of animals. Similarily insignificant changes (p>0.05) in serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH) and sections of different organs indicate inoffensive nature of both generations of PEGylated 4.0G and 5.0 G PPI dendrimers. Conclusion: It can be concluded that fifth-generation PPI dendrimers are more suitable as compared to fourth generation of PPI dendrimer, while both dendrimers are not generating any severe toxicity.

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