Telmisartan

Eight brands of Telmisartan tablets (40 mg) were purchased from a local pharmacy: Micardis^® (Boehringer Ingelheim, Sydney, Australia), DRLA^® (Dr Reddy’s Laboratories, Melbourne, Australia), APO^® (Apotex, Sydney, Australia), Mizart^® (Alphapharm, Ipswich, Australia), GH^® (Generic Health, Melbourne, Australia), Teltartan^® (Arrow Pharma, Melbourne, Australia), Sandoz^® (Sandoz, Sydney, Australia), and Pharmacor^® (Pharmacor, Sydney, Australia). All tablets were tested within their original expiry periods, and where chemical analyses were performed, tablets with the same batch number were used. Webster-pak^® 28 (Webstercare, Sydney, Australia) medication packs (small, heat-sealed) were employed for tablet repackaging.
Telmisartan of 99.8% purity from Tokyo Chemical Industry (Tokyo, Japan) was used for high performance liquid chromatography (HPLC) standard. Methanol (Fisher, Geel, Belgium; HPLC Grade), sodium hydroxide (Ajax Finechem, Sydney, Australia; analytical reagent), sodium acetate (Ajax Finechem, Sydney, Australia; analytical reagent), glacial acetic acid (Ajax Finechem, Sydney Australia; analytical reagent), and potassium dihydrogen phosphate (Scharlau, Sentmenat, Spain; reagent grade) were used to prepare HPLC mobile phase and buffers.

The test compound GSK1210151A (I-BET151) was developed at GSK^{21 (link)}. For this study, I-BET151 was prepared as a suspension in 0.5% (w/w) hydroxypropyl methylcellulose (HPMC) with 0.1% (w/w) Tween 80 to a final concentration of 5 mL/kg. Dosing was administered orally once daily at 5 mg/kg, 10 mg/kg or 15 mg/kg. The vehicle control was prepared using 1.0% (w/v) MethylCellulose (MC). For positive control, Telmisartan, an angiotensin II receptor antagonist (QW32M-GS), was purchased from Tokyo chemical industry CO. LTD. The stock solution of Telmisartan was prepared in a suspension containing 1.0% (w/v) MC to a final concentration of 5 mL/kg and dosed orally once a day at 10 mg/kg.

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).

Telmisartan was purchased from Tokyo Chemical Industry Co. (Tokyo, Japan). We prepared a stock solution of Telmisartan by diluting it to 10 mM with dimethyl sulfoxide (DMSO). The stock solution was stored at −20 °C.

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).