PXS-S2B, a small-molecule selective LOXL2 inhibitor (kindly provided by Pharmaxis Ltd., Frenchs Forest, Australia) was administered by daily oral gavage (10 mg/kg) through a flexible plastic gavage tube (Instech laboratories, USA). Telmisartan (Santa Cruz, CA, USA) was mixed in drinking water (2 mg/kg/d, pH7.4) as a comparative limb of current best practice. The dose chosen is not known to have any blood pressure lowering effect40 (link). Animals were divided into the following groups: 1) Control (Ctrl), 2) Diabetic (DM), 3) Diabetic receiving the LOXL2 inhibitor (DM + LOXL2i), 4) Diabetic receiving Telmisartan (DM + Telmi), 5) Diabetic receiving the LOXL2 inhibitor and Telmisartan (DM + Telmi + LOXL2i). Treatment was carried out for 24 weeks from diagnosis of diabetes. At the time of culling, kidneys were perfused in ice-cold PBS before harvest and snap frozen in liquid nitrogen or fixed in 10% neutral buffered formalin for 24 hours prior paraffin embedding.
Telmisartan
Manufactured by Santa Cruz Biotechnology
Sourced in United States
Telmisartan is a laboratory product provided by Santa Cruz Biotechnology. It is a chemical compound commonly used for research purposes.
Automatically generated - may contain errors
3 protocols using telmisartan
1
Evaluation of LOXL2 Inhibitor in Diabetic Kidney Disease
2
Ang II-Induced Macrophage and Vascular Smooth Cell Response
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Mouse macrophage cell line Raw264.7 and mouse aorta vascular smooth cell line (MOVAS) were purchased from ATCC and cultured in Dulbecco Modified Eagle's Medium/High Glucose (DMEM/H) medium supplemented with 10% fetal bovine serum, 100 U/mL penicillin, and 100 mg/mL streptomycin. CHO‐K1 stably expressing AT1R was purchased from PerkinElmer (Shanghai, China) and cultured in DMEM/F12 medium containing 10% fetal bovine serum, 100 U/mL penicillin, and 100 mg/mL streptomycin. All these cells are maintained at 37°C in a humidified 5% CO2 incubator. For stimulation, MOVAS cells were pretreated with the anti‐ATR‐001 antibody (10 μg/mL), telmisartan (1×10−6 mol/L), or the normal mouse immunoglobulin G (Santa Cruz Biotechnology, sc‐2025) for 2 hours, respectively, subsequently stimulated by Ang II (1×10−5 mol/L) for 72 hours. And Raw264.7 cells were pretreated with the anti‐ATR‐001 antibody (10 μg/mL), telmisartan (1×10−6 mol/L), or the normal mouse immunoglobulin G for 2 hours, respectively, subsequently stimulated by Ang II (1×10−5 mol/L) for 24 hours.
3
Telmisartan and Fructose Metabolism
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Sera for biochemical analyses were collected from BN rats treated with Telmisartan and fructose, and from the separate groups of SHR (i-iv as above) on day 13 of treatment. Biochemical parameters in urine and sera were performed in clinical laboratories of the Institute for Clinical and Experimental Medicine in Prague.
Telmisartan and Telmisartan acyl-β-Dglucuronide were purchased from Santa Cruz Biotechnology (CA, USA). All solvents and chemicals were of MS grade, bought from Sigma Aldrich. For quantitation of Telmisartan and its glucuronide conjugate, liver samples (~50 mg) were homogenized in 0.5 ml of methanol and 0.5 ml of acetonitrile using a bead mill MM400 (Retsch, Germany), centrifuged 12,000 g at 4 °C for 10 min, supernatants filtered and stored at -80 °C until LC-MS/MS analysis. Differential ion mobility mass spectrometry system SelexION/QTRAP 5500 (Sciex, USA) coupled to UPLC Dionex 3000 RSLC (Thermo, USA) was used to quantify analytes. Telmisartan and Telmisartan glucuronide were separated using C8 Kinetex column (50x2.1 mm, 1.7 µm, 100 A, Phenomenex, USA) and gradient elution as described before (Yan et al. 2008) .
Telmisartan and Telmisartan acyl-β-Dglucuronide were purchased from Santa Cruz Biotechnology (CA, USA). All solvents and chemicals were of MS grade, bought from Sigma Aldrich. For quantitation of Telmisartan and its glucuronide conjugate, liver samples (~50 mg) were homogenized in 0.5 ml of methanol and 0.5 ml of acetonitrile using a bead mill MM400 (Retsch, Germany), centrifuged 12,000 g at 4 °C for 10 min, supernatants filtered and stored at -80 °C until LC-MS/MS analysis. Differential ion mobility mass spectrometry system SelexION/QTRAP 5500 (Sciex, USA) coupled to UPLC Dionex 3000 RSLC (Thermo, USA) was used to quantify analytes. Telmisartan and Telmisartan glucuronide were separated using C8 Kinetex column (50x2.1 mm, 1.7 µm, 100 A, Phenomenex, USA) and gradient elution as described before (Yan et al. 2008) .
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