Anna Gorąca1, Paulina Kleniewska2, Beata Skibska3. 1. Experimental and Clinical Physiology, Department of Cardiovascular Physiology, Medical University of Lodz, Łódź, Poland. Electronic address: anna.goraca@umed.lodz.pl. 2. Department of Immunopathology, Faculty of Biomedical Sciences and Postgraduate Training, Medical University of Lodz, Łódź, Poland. 3. Department of Applied Pharmacy, Department of Pharmacy, Medical University of Lodz, Łódź, Poland.
Abstract
BACKGROUND: The aim of this study was to determine the involvement of protein kinase C (PKC) in the ET-1 induced generation of reactive oxygen species and TNF-α in rat lungs. METHODS: Experiments were performed on 6 groups of rats: Group I: saline-treated control; Group II: saline followed by endothelin-1 (ET-1) (3μg/kg); Group III: saline followed by selective PKC αβ1 inhibitor (Gö6976) (2μg/kg); Group IV: Gö6976 (2μg/kg) administered 30min before ET-1 (3μg/kg); Group V: saline followed by the PKC activator phorbol 12-myristate 13-acetate (PMA) (50μg/kg); Group VI: Gö6976 (2μg/kg) administered 30min before PMA (50μg/kg). After 5h, the animals were euthanized and their lungs were isolated for measurements. RESULTS: ET-1 resulted in increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels and lung edema, as well as a decrease in GSH/GSSG ratio compared to the controls. The level of TNF-α also was elevated in the presence of ET-1. Administration of Gö6976 30min before ET-1 injection significantly decreased lung edema, as well as the concentrations of TBARS, H2O2 and TNF-α, but increased the GSH/GSSG redox ratio compared to ET-1. Conversely, PMA elevated lung edema and TBARS, H2O2 and TNF-α concentrations, but decreased the GSH/GSSG redox ratio compared to the control group. Treatment with Gö6976 significantly ameliorated the PMA-induced oxidative stress parameters, decreased tissue TNF-α level, and lung edema. CONCLUSION: Endothelin-1 induces ROS generation, increases TNF-α level and lung edema via activation of PKC αβ1.
BACKGROUND: The aim of this study was to determine the involvement of protein kinase C (PKC) in the ET-1 induced generation of reactive oxygen species and TNF-α in rat lungs. METHODS: Experiments were performed on 6 groups of rats: Group I: saline-treated control; Group II: saline followed by endothelin-1 (ET-1) (3μg/kg); Group III: saline followed by selective PKC αβ1 inhibitor (Gö6976) (2μg/kg); Group IV: Gö6976 (2μg/kg) administered 30min before ET-1 (3μg/kg); Group V: saline followed by the PKC activator phorbol 12-myristate 13-acetate (PMA) (50μg/kg); Group VI: Gö6976 (2μg/kg) administered 30min before PMA (50μg/kg). After 5h, the animals were euthanized and their lungs were isolated for measurements. RESULTS:ET-1 resulted in increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels and lung edema, as well as a decrease in GSH/GSSG ratio compared to the controls. The level of TNF-α also was elevated in the presence of ET-1. Administration of Gö6976 30min before ET-1 injection significantly decreased lung edema, as well as the concentrations of TBARS, H2O2 and TNF-α, but increased the GSH/GSSG redox ratio compared to ET-1. Conversely, PMAelevated lung edema and TBARS, H2O2 and TNF-α concentrations, but decreased the GSH/GSSG redox ratio compared to the control group. Treatment with Gö6976 significantly ameliorated the PMA-induced oxidative stress parameters, decreased tissue TNF-α level, and lung edema. CONCLUSION:Endothelin-1 induces ROS generation, increases TNF-α level and lung edema via activation of PKC αβ1.
Authors: Yaritza Inostroza-Nieves; Shirley Valentin-Berrios; Christopher Vega; Gregory N Prado; Claribel Luciano-Montalvo; José R Romero; Alicia Rivera Journal: BMC Complement Med Ther Date: 2022-04-07