scholarly journals Study on the Mechanism of Reducing Hepatotoxicity of Water-Grinding Realgar by Metabolomics, Morphology, and Chemical Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Ting Han ◽  
Hui Zhang ◽  
Wenjuan Xu ◽  
Chunshuai Li ◽  
Min Wang ◽  
...  
Keyword(s):  
Acid Metabolism ◽  
Histopathological Examination ◽  
Liver Weight ◽  
Arachidonic Acid Metabolism ◽  
Control Group ◽  
High Dose ◽  
Grinding Method ◽  
Significant Toxicity ◽  
Male Wistar Rats ◽  
Metabolomics Analysis

Background. Realgar was usually selected as a substitute for arsenic trioxide to treat acute promyelocytic leukemia due to its higher effect without high cardiotoxicity. In traditional Chinese medicine (TCM), realgar is usually processed by the water-grinding method clinically, but the mechanism of realgar processing detoxification is still unclear. However, it is necessary to take safety and efficacy into account while evaluating a drug. Methods. Sixty male Wistar rats were divided into control group, realgar products-treated groups, and corresponding subgroups. Biochemistry analysis and histopathological examination were performed in the study, and plasma samples were collected from all the rats for metabolomics analysis. Results. No significant toxicity was observed in rats treated with 0.64 g/kg/day grinding realgar (G-r) and water-grinding realgar (WG-r). When the dose increased to 1.92 g/kg/day, the liver weight coefficients of the rats treated with G-r (HG-r: 3.65 ± 0.26%) and WG-r (HWG-r: 3.67 ± 0.14%) increased significantly and severe hepatic injury occurred in comparison to the control group (Group C: 3.00 ± 0.21%). After one week's withdrawal, the liver injury caused by the high dose of WG-r significantly recovered, while the liver damage caused by G-r was more difficult to recover. In metabolomics analysis, 14 metabolites were identified as the potential biomarkers in realgar-treated rats. These metabolites indicated that there were perturbations of the primary bile acid biosynthesis, arachidonic acid metabolism, linoleic acid metabolism, and glycerophospholipid metabolism in the realgar-treated groups. Conclusions. These results illustrate that, as a TCM processing method, water grinding had the effect of reducing toxicity, and the metabolomics method may be a valuable tool for studying the toxicity induced by TCM and the mechanism of TCM processing.

scholarly journals Andrographolide Against Lung Cancer-New Pharmacological Insights Based on High-Throughput Metabolomics Analysis Combined with Network Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Luo ◽  
Li Jia ◽  
Jia-Wen Zhang ◽  
Dong-Jie Wang ◽  
Qiu Ren ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Throughput ◽  
Acid Metabolism ◽  
Pharmacological Action ◽  
Arachidonic Acid Metabolism ◽  
Metabolic Effects ◽  
Network Pharmacology ◽  
Control Group ◽  
Protective Effects ◽  
Metabolomics Analysis

Andrographolide (Andro) has known to treat various illnesses such as colds, diarrhea, fever and infectious diseases. However, the effect mechanism of Andro is still unclear. Therefore, we used high-throughput metabolomics analysis to discover biomarkers, metabolic profiles and pathways to reveal the pharmacological action and effective mechanism of Andro against lung cancer. The metabolic effects of Andro on lung cancer animal was explored by ultra-performance liquid chromatography-triple-time of flight/mass spectrometry (UPLC-TOF/MS) analysis. Our results showed that Andro exhibited significant protective effects against lung cancer. Compared with control group, a total of 25 metabolites biomarkers was identified in urine of model animals, which 18 of them were regulated toward the normal direction after Andro treatment, and network pharmacology analysis showed that they were related with 570 proteins. Biological pathways analysis showed that the 11 metabolism pathways were regulated by Andro treatment in lung cancer mouse, and amino acid metabolism and arachidonic acid metabolism have great potential as target pathways for Andro against lung cancer. It revealed that high-throughput metabolomics combined with network pharmacology analysis provides deeply insight into the therapeutic mechanisms of natural product for promoting medicine development and disease treatment.

scholarly journals Quantitation, Absorption and Tissue Distribution of Coenzyme Q10 from Pak-wanban (Sauropus androgynus L. Merr.) Leaf and Its Antioxidant Activities

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Aikkarach KETTAWAN ◽  
Kansuda WUNJUNTUK
Keyword(s):  
Tissue Distribution ◽  
Coenzyme Q10 ◽  
Antioxidant Activities ◽  
Alpha Tocopherol ◽  
Control Group ◽  
High Dose ◽  
Cooking Oil ◽  
Supplement Group ◽  
Male Wistar Rats ◽  
Plasma Antioxidant

Pak-wanban (Sauropus androgynus L. Merr.), a popular Thai vegetable, has been found to have a high content of Coenzyme Q10 (CoQ10), which is a powerful antioxidant. This study investigated the quantitation, absorption and tissue distribution of CoQ10 from raw and stir-fried Pak-wanban and its antioxidant activities in rats. Male Wistar rats (seven weeks old) were randomly grouped as follows: (1) control, (2) raw Pak-wanban powder of 0.5 mg CoQ10/kg/day, (3) stir-fried Pak-wanban powder of 0.5 mg CoQ10/kg/day, (4) stir-fried Pak-wanban powder of 1.0 mg CoQ10/kg/day, and (5) commercially CoQ10 supplement groups of 0.5 mg CoQ10/kg/day. The results found that stir-fried cooking did not significantly reduce the content of CoQ10 in the Pak-wanban leaves. After 3 weeks of experimentation, the level of CoQ10 in the plasma, liver and spleen was increased in all Pak-wanban groups when compared to the control group. The level of CoQ10 in the stir-fried Pak-wanban group was significantly higher than the raw Pak-wanban group but slightly lower than the CoQ10 supplement group.  Liver alpha-tocopherol concentrations were markedly increased in rats that consumed a high dose of CoQ10 from stir-fried Pak-wanban of 1 mg of CoQ10/kg/day when compared with the control group. Plasma antioxidant activities (ORAC: FRAP: DPPH) were significantly increased in both groups of stir-fried Pak-wanban when compared with the control group. We concluded that CoQ10 in  Pak-wanban could be well absorbed and improved the plasma antioxidant activities. Furthermore, cooking oil may increase the bioavailability of CoQ10 from vegetables. Therefore, it would be useful for vegetarian people.

scholarly journals Lomatogonium Rotatum for Treatment of Acute Liver Injury in Mice: A Metabolomics Study

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 227 ◽  
Author(s):  
Renhao Chen ◽  
Qi Wang ◽  
Lanjun Zhao ◽  
Shilin Yang ◽  
Zhifeng Li ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Liver Injury ◽  
Acid Metabolism ◽  
Acute Liver Injury ◽  
Tca Cycle ◽  
Arachidonic Acid Metabolism ◽  
Hepatoprotective Effect ◽  
Metabolomics Study ◽  
Metabolomics Analysis

Lomatogonium rotatum (L.) Fries ex Nym (LR) is used as a traditional Mongolian medicine to treat liver and bile diseases. This study aimed to investigate the hepatoprotective effect of LR on mice with CCl4-induced acute liver injury through conventional assays and metabolomics analysis. This study consisted of male mice (n = 23) in four groups (i.e., control, model, positive control, and LR). The extract of whole plant of LR was used to treat mice in the LR group. Biochemical and histological assays (i.e., serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and histological changes of liver tissue) were used to evaluate LR efficacy, and metabolomics analysis based on GC-MS and LC-MS was conducted to reveal metabolic changes. The conventional analysis and metabolomic profiles both suggested that LR treatment could protect mice against CCl4-induced acute liver injury. The affected metabolic pathways included linoleic acid metabolism, α-linolenic acid metabolism, arachidonic acid metabolism, CoA biosynthesis, glycerophospholipid metabolism, the TCA cycle, and purine metabolism. This study identified eight metabolites, including phosphopantothenic acid, succinic acid, AMP, choline, glycerol 3-phosphate, linoleic acid, arachidonic acid, and DHA, as potential biomarkers for evaluating hepatoprotective effect of LR. This metabolomics study may shed light on possible mechanisms of hepatoprotective effect of LR.

scholarly journals Neurotoxic Effects of Stanozolol on Male Rats‘ Hippocampi: Does Stanozolol cause apoptosis?

2019 ◽  
Vol 10 (1) ◽  
pp. 73-81
Author(s):  
Faezeh Nemati Karimooy ◽  
Alireza Ebrahimzadeh Bideskan ◽  
Abbas Mohammadi Pour ◽  
Seyed Mahmoud Hoseini
Keyword(s):  
Histopathological Examination ◽  
Apoptotic Cell ◽  
Cell Formation ◽  
Treated Group ◽  
Male Rats ◽  
Control Group ◽  
Cell Detection ◽  
Apoptotic Effect ◽  
Male Wistar Rats ◽  
The Mean

AbstractStanozolol is an anabolic-androgenic steroid which is commonly abused by athletes for improved energy, appearance, and physical size. It has been previously shown to cause changes in behaviour and has various physical effects. Studies have previously been conducted on its neurotoxic effect on the central nervous system (CNS), which are typically psychological in nature. This study was performed to investigate the apoptotic effect of stanozolol on different parts of the rat hippocampus. Sixteen male Wistar rats were divided randomly into two groups (experimental and control). The experimental group received subcutaneous injections of stanozolol (5mg/kg/day) for consecutive 28 days, whereas the control group received saline using the same dosing schedule and administration route. After routine procedures, coronal sections of rat brain were stained with Toluidine blue and TUNEL for pre-apoptotic and apoptotic cell detection, respectively. In order to compare groups, the mean number of TUNEL-positive and pre-apoptotic neurons per unit area were calculated and analysed. Histopathological examination revealed that the mean number of pre-apoptotic and apoptotic neurons in the CA1, CA2, CA3 and DG areas of the hippocampus were significantly increased in the stanozolol treated group. In conclusion, stanozolol abuse may induce pre-apoptotic and apoptotic cell formation in different regions of the hippocampus.

scholarly journals The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach

2015 ◽  
Vol 36 (3) ◽  
pp. 988-1003 ◽  
Author(s):  
Hamed Karimian ◽  
Mehran Fadaeinasab ◽  
Soheil Zorofchian Moghadamtousi ◽  
Maryam Hajrezaei ◽  
Maryam Zahedifard ◽  
...  
Keyword(s):  
Sesquiterpene Lactone ◽  
Histopathological Examination ◽  
Cancer Control ◽  
Control Group ◽  
High Dose ◽  
Mcf7 Cells ◽  
Carcinogenic Effect ◽  
Chemopreventive Effect

Background: Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models. Methods and Results: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels. Conclusion: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.

scholarly journals Antiskin Cancer and Antioxidant Activities of Formulated Agar from Brown Seaweed Laminaria digitata (Hudson) in Dimethyl Benzanthracene-Induced Swiss Albino Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jeneesha George ◽  
A. Thabitha ◽  
N. Vignesh ◽  
V. Manigandan ◽  
R. Saravanan ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Histopathological Examination ◽  
Brown Seaweed ◽  
Cancer Control ◽  
In Vitro Cytotoxicity ◽  
Control Group ◽  
High Dose ◽  
Laminaria Digitata ◽  
Group 2

This study explores the antiskin cancer effect of formulated agar (FA) from Laminaria digitata on dimethyl benzanthracene- (DMBA-) induced skin cancer mice. The agar was extracted and formulated (emulgel), and FA was biochemically characterized. The in vitro cytotoxicity of FA was tested using NTT 3T3 mice fibroblast cells. The mice were divided into 5 groups: group 1 served as control mice, group 2 mice were considered as DMBA-induced cancer control, group 3 mice were FA pretreated (low dose) + DMBA-induced mice, group 4 mice were FA pretreated (high dose) + DMBA-induced mice, and group 5 were positive control + DMBA-induced mice. The behaviour and biochemical markers of cancer were significantly decreased in group 2 (DMBA-induced) mice, which were brought to near normalcy by FA pretreated mice (groups 3 and 4). The levels of p53 and keratin were significantly elevated in group 2 mice and these levels were decreased in 3 and 4 mice as well. The histopathological examination of DMBA-induced mice was shown degenerated cervical patches in the skin, cirrhosis in liver, oedema in the renal tissue, and swollen and damage in cardiac tissue, which were reduced for the mice applied with FA. This confirms that FA pretreatment offered potential antiskin cancer property.

scholarly journals Effects of Steroidal and Nonsteroidal Drugs on Tooth Movement and Root Resorption in the Rat Molar

2009 ◽  
Vol 79 (4) ◽  
pp. 715-726 ◽  
Author(s):  
Carmen Gonzales ◽  
Hitoshi Hotokezaka ◽  
Ken-Ichiro Matsuo ◽  
Tatsunori Shibazaki ◽  
Joseph H. Yozgatian ◽  
...  
Keyword(s):  
Tooth Movement ◽  
Root Resorption ◽  
Three Dimensional ◽  
Negative Control Group ◽  
Treated Group ◽  
Negative Control ◽  
Control Group ◽  
High Dose ◽  
Experimental Control ◽  
Male Wistar Rats

Abstract Objective: To test the hypothesis that the administration of aspirin, acetaminophen, meloxicam, celecoxib, and prednisolone have no effect on root resorption and tooth movement. Materials and Methods: A mesial force of 50 g was applied to the left maxillary first molars of sixty 10-week-old male Wistar rats using nickel titanium closed coil springs attached to the cervical area of the incisors. The rats were randomly divided into 12 groups of 5 each. High and low doses of aspirin, acetaminophen, meloxicam, celecoxib, and prednisolone were administered via drinking water for 2 weeks. The experimental control group had tooth movement but received no drug. The negative control group received neither tooth movement nor drugs. The amount of tooth movement was measured on digitized lateral cephalometric radiographs. Rats were sacrificed after 2 weeks. Mesial and distal roots (distobuccal and distopalatal) were examined using scanning electron and three-dimensional (3D) scanning laser microscopes. The surface area, depth, volume, and roughness of the root resorption craters were measured. Results: When compared with experimental control rats, only prednisolone- and high-dose celecoxib-treated groups showed significantly less root resorption and less tooth movement. Although low dose celecoxib-treated group significantly decreased the tooth movement, root resorption was similar to the control group. Furthermore, resorption craters showed a smoother surface in the prednisolone-treated rats. Conclusions: The hypothesis was rejected. Administration of prednisolone and high-dose celecoxib reduces root resorption and interferes with tooth movement in rats. Both drugs may interfere in the arachidonic acid cascade depending on dose thresholds.

scholarly journals The study of Yangyinyiqi mixture anti bleomycin-induced pulmonary fibrosis on rats by intervening matrix metalloproteinase-9 and tissue inhibitors of matrix metalloproteinases-1

2021 ◽  
Vol 20 (3) ◽  
pp. 315-323
Author(s):  
Hong Wang ◽  
◽  
Chen-Yu Chen ◽  
Yong Zhu ◽  
Ji-Pu Zhou ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Dose Group ◽  
Histopathological Examination ◽  
Control Group ◽  
High Dose ◽  
Distilled Water ◽  
Model Group ◽  
Dexamethasone Acetate ◽  
And Control ◽  
Metalloproteinase 9

To investigate effectsof Yangyinyiqi Mixture on pulmonary fibrosis caused by bleomycin. SD ratswere divided randomly into: model group(distilled water,1 mL·0.1 kg-1), dexamethasone acetate group(dexamethasone acetate, the dosage was reduced gradually), low-dose group(Yangyinyiqi Mixture, 11 g·kg-1), moderate-dose group(Yangyinyiqi Mixture, 22 g·kg-1), high-dose group (Yangyinyiqi Mixture, 44 g·kg-1) and control group(distilled water, 1 mL·0.1 kg-1). Yangyinyiqi Mixture and dexamethasone acetate were intragastrically administrated. Lung tissue was collected for histopathological examination. Compared with control group, collagen markedly increased andHYP content significantly increased on 7th day in model group (p<0.01). On 28th day, collagen was diffusely deposited, alveolar was destroyed, and HYP content significantly increased (p<0.01). Compared with model group, bleomycin-induced suffering injury caused MMP-9 expression levels to rapidly increase (7and 14 days, p<0.01). TIMP-1 markedly increased (7and 14 days, p<0.01) and stayed at a high levelto28th day. Yangyinyiqi Mixture exerted an effect against pulmonary fibrosis, which could involved prevention of collagen deposition through inhibitingMMP-9 and TIMP-1 expression.

scholarly journals THE HIGH DOSE TOXICITY OF BETEL NUT (Areca catechu L.) ON REPRODUCTION ORGAN OF RATS

2019 ◽  
Vol 7 (1) ◽  
pp. 41-49
Author(s):  
Ave Olivia Rahman ◽  
Herlambang Herlambang ◽  
Charles A Simanjuntak ◽  
Hasna Dewi ◽  
Ahmad Syauqy ◽  
...  
Keyword(s):  
Rattus Norvegicus ◽  
Histopathological Examination ◽  
Herbal Medicines ◽  
Reproductive Organs ◽  
Control Group ◽  
High Dose ◽  
Betel Nut ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Areca Catechu

ABSTRACT Background : The use of long-term herbal medicines and high doses can damage organs, including the reproductive organs. Betel nut (Areca catechu L.) is one of the herbal ingredients that is consumed as a stamina enhancing beverage. The purpose of this study was to determine the effect of longterm treatment of raw betel nut at a dose of 10,000 mg/kg on testicular and ovary tissue of rats. Rats were Rattus norvegicus, Sprague Dawley strain, 2-3 months.  Methods : Tweenty rats divided into 2 groups, each groups were 5 male and 5 female. Control group was given aquades and the treatment group was given raw betel nut with a dose of 10,000 mg/kgBW for 45 days with a gastrictube. Histopathological examination with Haematoxylin-Eosin staining was used to assses testicular and ovary tissues.  Results: The ovaries of treatment groups had significantly lower de graff follicle compared to the control group (p < 0,05). The testis of treatment groups had significantly smaller diameter of tubulus seminifery, significantly higher necrosis of spermatogonia and spermatosit (p<0,05). Conclusion: Treatment of raw betel nut dose 10,000 mg /kgBW along 45 days causes damage of  testicular and ovary tissues of rats.Keywords:  Betel Nut, Areca Catechu L., Histopathology, Testicular, Ovary, Herbal Toxicity   ABSTRAK Latar Belakang: Pemakaian obat herbal jangka panjang dan dosis tinggi dapat menyebabkan kerusakan organ tubuh, termasuk organ reproduksi. Biji pinang (Areca catechu L.) merupakan salah satu bahan herbal yang dikonsumsi sebagai minuman penambah stamina.Tujuan penelitian ini adalah untuk mengetahui pengaruh pemberian biji pinang muda dosis 10.000 mg/ kgBB selama 45 hari terhadap gambaran histopatologis testis dan ovarium tikus. Metode : Tikus yang digunakan adalah Rattus norvegicus galur Spague Dawley, usia 2-3 bulan, sebanyak 10 ekor jantan dan 10 ekor betina yang dibagi menjadi 2 kelompok, yaitu kelompok kontrol diberikan aquades dan kelompok perlakuan diberikan biji pinang dosis 10.000 mg/ kgBB  dengan sonde. Pemeriksaan histopatologi dengan pewarnaan Haematoxylin-Eosin untuk organ testis dan organ ovarium. Hasil: Jumlah folikel de draf pada kelompok perlakuan  lebih sedikit dibandingkan kelompok kontrol (p<0,05).  Persentase nekrosis spermatogonia dan spermatosit pada kelompok perlakuan  lebih tinggi dibandingkan kelompok kontrol (p<0,05), diameter tubulus seminifeus pada kelompok perlakuan juga lebih kecil dibandingkan kelompok kontrol (p<0,05). Kesimpulan: Pemberian biji pinang 10.000 mg/kgBB selama 45 hari menyebabkan kerusakan pada jaringan testis dan ovarium pada tikus.  Kata Kunci           :  Biji Pinang,  Areca Catechu L, Histopatologi, Ovarium, Testis, Toksisitas herbal

scholarly journals Monosodium glutamate alter hepatic functions, redox potential and lipid metabolism: Omega 3 fatty acids ameliorative intervention

2020 ◽  
Vol 13 (1) ◽  
pp. 101-110
Author(s):  
Divine Avwerosuoghene Onobrudu ◽  
Barine Innocent Nwiloh
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Monosodium Glutamate ◽  
Control Group ◽  
High Dose ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Male Wistar Rats ◽  
High Doses ◽  
Global Health Challenge

Monosodium glutamate (MSG) toxicity is fast becoming a global health challenge due to the increase in its consumption as a food additive. This study investigated the effect of consumption of MSG and treatment with graded doses of omega 3 fatty acids (ω-3). Forty-eight male Wistar rats (n=8) grouped into six; control, MSG, MSG + Low dose of ω-3 (LD ω-3); MSG + High dose of ω-3 (HD ω-3), LD ω-3, and HD ω-3 were used for this study. MSG was administered at 4 g/L/day in their drinking water for 6 weeks, while ω-3 was administered at low and high doses of 100 and 300 mg/kg BW, p.o. respectively for 4 weeks. Results revealed that administration of MSG induced imbalance in lipid metabolism, oxidative stress and hepatic dysfunction. These were revealed by significant decreases in TG, HDL-C, CAT, GSH, albumin and total protein; but, significant increases in LDL-C, MDA, AST, ALT, ALP, and total bilirubin (TB), compared to control group. Administration of graded doses of ω-3 following treatment with MSG was characterized with significant reductions in ALT, ALP, TB and MDA. The administration of ω-3 showed no effects on the antioxidant indices. Conclusively, LD ω-3 is a potent ameliorative supplement which can be administered after pre-exposure to MSG.

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