Eight-week-old male C57BL/6NCrSlc mice (Japan SLC, Inc., Hamamatsu, Japan) were caged with free access to food and water and kept at 23 ± 3 °C with 50 ± 20% humidity and a 12 h light/dark cycle. Overall, 50 mice were randomly divided into 5 experimental groups (n = 10) and underwent treatment for 8 weeks as follows (Figure 1 A): (i) intraperitoneal injection of corn oil and oral gavage of saline as a vehicle (C/O group); (ii) intraperitoneal injection of CCl4 (FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan) twice a week (1 mL/kg) and vehicle (CCl4 + Veh group); (iii) CCl4 and oral gavage of sacubitril (30 mg/kg) (Tokyo Chemical Industry, Tokyo, Japan) (CCl4 + SAC group); (iv) CCl4 and oral gavage of valsartan (30 mg/kg) (Tokyo Chemical Industry) (CCl4 + VAL group); and (v) CCl4 and oral gavage of sacubitril and valsartan (30 mg/kg each) (CCl4 + SAC/VAL group) [24 (link),25 (link),26 (link)]. After 8 weeks, all of the mice were intravenously injected with pentobarbital sodium (150 mg/kg), subjected to anesthesia, and then their blood and livers were collected immediately after euthanasia. Serum levels of biochemical markers were assessed at SRL, Inc. (Tokyo, Japan).
Valsartan
Manufactured by Tokyo Chemical Industry
Sourced in Japan
Valsartan is a laboratory product manufactured by Tokyo Chemical Industry. It is a chemical compound used for research and development purposes. Its core function is to serve as a reference standard or analytical tool for various scientific applications.
Automatically generated - may contain errors
Lab products found in correlation
Telmisartan, by Tokyo Chemical Industry (3 mentions)
Irbesartan, by Fujifilm (2 mentions)
Losartan, by Fujifilm (2 mentions)
Losartan, by Merck Group (1 mentions)
Enalapril, by Merck Group (1 mentions)
Amlodipine, by Merck Group (1 mentions)
Nifedipine, by Tokyo Chemical Industry (1 mentions)
Digoxin, by Merck Group (1 mentions)
Sulfameter, by Merck Group (1 mentions)
Furosemide, by Tokyo Chemical Industry (1 mentions)
Atenolol, by Merck Group (1 mentions)
Simvastatin, by Merck Group (1 mentions)
Atorvastatin, by Merck Group (1 mentions)
Fenofibrate, by Tokyo Chemical Industry (1 mentions)
Propranolol, by Merck Group (1 mentions)
Lc ms grade acetonitrile, by Avantor (1 mentions)
Sacubitril, by Tokyo Chemical Industry (1 mentions)
C57bl 6ncrslc mice, by Japan SLC (1 mentions)
Ketoprofen, by Merck Group (1 mentions)
Lopinavir, by LGC (1 mentions)
8 protocols using valsartan
1
CCl4-Induced Liver Injury Model in Mice
2
Quantitative Bioanalytical Workflow
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LC-MS grade acetonitrile, methanol, and water were purchased from J.T. Baker (Milwaukee, WI, USA). Amlodipine, atenolol, atorvastatin, digoxin, enalapril, losartan, propranolol, simvastatin, and sulfameter were purchased from Sigma–Aldrich (St. Louis, MO, USA). Fenofibrate, furosemide, nifedipine, and valsartan were purchased from Tokyo Chemical Industry (Tokyo, Japan). Whatman 903 blood sampling cards were purchased from GE Healthcare (Westborough, MA, USA). Human whole blood with EDTA was purchased from Innovative Research (Novi, MI, USA), which is a supplier of human blood samples. Experimental usage of human blood was approved by the Institutional Review Board of Seoul National University (IRB NO. E1605/003-003).
3
Characterization of FITC-labeled Biomaterials
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FITC-PLL (FITC-linker-K-K-K-K-K; purity >93%; 1,160 Da) was purchased from Peptron Inc. (Daejeon, Korea). FITC-HA (purity >95%; 10,000 Da) was purchased from Creative PEGWorks Co. (Chapel hill, NC). Vitamin C, ketoprofen, and sodium lauryl sulfate (SLS) were purchased from Sigma-Aldrich Chemical Co. (St. Louis, MO). Ketotop® patch was purchased from Handok Pharmaceutical Co., Ltd. (Seoul, Korea). Lopinavir was purchased from Toronto Research Chemicals Inc. (Toronto, Ontario, Canada). Valsartan was purchased from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan). All other reagents were of analytical grade and used without further purification
4
Preparation and Storage of Angiotensin II Receptor Antagonists
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Telmisartan and valsartan were purchased from Tokyo Chemical Industry Co. (Tokyo, Japan). Losartan and irbesartan were purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). We prepared solutions of Telmisartan, valsartan and irbesartan by diluting with dimethyl sulfoxide (DMSO). Losartan was prepared by diluting with H2O. The stock solutions were stored at −20°C.
5
Apoptosis Regulation by Angiotensin II Receptor Antagonists
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Telmisartan, irbesartan, and valsartan were purchased from Tokyo Chemical Industry (Tokyo, Japan). We used caspase inhibitor Z‐VAD‐FMK [Medical and Biological Laboratories (MBL), Nagoya, Japan], STF‐62247 (Merck Millipore, Darmstadt, Germany), and Bafilomycin A1 (Adipogen, Epalinges, Switzerland).
Primary antibodies against apoptosis‐inducing factor (AIF), β‐actin, and histone H1 were purchased from Cell Signaling Technology (Beverly, CA, USA). Anti‐LC3 antibody was obtained from MBL. We used horseradish peroxidase‐conjugated secondary antibodies (Vector Laboratories, Burlingame, CA, USA).
Primary antibodies against apoptosis‐inducing factor (AIF), β‐actin, and histone H1 were purchased from Cell Signaling Technology (Beverly, CA, USA). Anti‐LC3 antibody was obtained from MBL. We used horseradish peroxidase‐conjugated secondary antibodies (Vector Laboratories, Burlingame, CA, USA).
6
Rat Lung Fibroblast Angiotensin II Responses
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Rat lung fibroblasts were isolated from 3-week-old Wistar rats using a trypsin digestion method and were maintained in complete culture medium [DMEM (BI-SH0019, BI, Kibbutz Beit-Haemek, Israel) supplemented with 10% fetal bovine serum (FBS, 10099141, Gibco, Thermo Fisher Scientific) and 100 U/ml penicillin/streptomycin] in a 37 °C incubator with 5% CO2. Cells at 80% confluence were cultured in FBS-free MEM medium for 24 hours, when most cells were in quiescent state. Next, the cells were divided into 6 groups and were cultured for 24 hours: 1) control; 2) 100 nmol/L Ang II (A9525, Sigma-Aldrich); 3) Ang II + 10−8 mol/L Ac-SDKP (H-1164, Bachem AG, Switzerland); 4) Ang II + 10−6 mol/L valsartan (V0112, Tokyo Chemical Industry, Tokyo, Japan); 5) Ang II + 10−6 mol/L TCS HDAC6 20b (4805, Tocris Bioscience, Bristol, United Kingdom); 6) Ang II + 10−3 mol/L Y-27632 (10005583 m, Cayman Chemical Company, Ann Arbor, MI, USA).
7
Quantitative Analysis of Valsartan and Its Impurities
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The commercial reagents of valsartan, cilnidipine, and NDMA with high purity (>98.0%, >98.0% and >99%, respectively) were purchased from Tokyo Chemical Industry Co., Ltd (Tokyo, Japan). APIs and its tablet formulations were provided by each company through the MHLW (Table 3 ).
valsartan APIs and its products analyzed in this study.
| Product name | Manufacturer | Tested sample | Supplier |
|---|---|---|---|
| valsartan TABLET 80 mg [AA] | ASKA Pharmaceutical Co., Ltd. | Substance | Zhejiang Huahai Pharmaceutical Co., Ltd. |
| Tablets | |||
| valsartan TABLETS 80 mg [SAWAI] | SAWAI Pharmaceutical Co., Ltd. | Substance | Zhejiang Tianyu Pharmaceutical Co., Ltd. |
| valsartan TABLET 80 mg [OHARA] | OHARA Pharmaceutical Co., Ltd. | Substance | |
| valsartan TABLETS 80 mg [SANOFI] | Nihon Pharmaceutical Industry Co., Ltd. | Substance | |
| Tablets | |||
| ATEDIO® Combination Tab. | EA Pharma Co., Ltd. | Substance | |
| Tablets |
8
Angiotensin II Receptor Antagonist Preparation
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Telmisartan and valsartan were purchased from Tokyo Chemical Industry Co. (Tokyo, Japan). Irbesartan and losartan were purchased from Wako Pure Chemical Industries (Osaka, Japan). Telmisartan was prepared as a 10 mM stock solution in dimethyl sulfoxide (DMSO). Irbesartan and valsartan were prepared as 100 mM stock solutions in DMSO, and losartan was prepared as a 100 mM stock solution in H2O. The stock solutions were stored at -20°C. Compound C was purchased from Abcam (Cambridge, UK). MK-2206 was purchased from ChemScene Chemicals (Monmouth Junction, NJ, USA). SCH772984 was purchased from Selleck Chemicals (Houston, TX, USA).
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