The effects of tadalafil and pentoxifylline on apoptosis and nitric oxide synthase in liver ischemia/reperfusion injury

Abstract

The aim of this study was to investigate the effects of tadalafil (TDF) and pentoxifylline (PTX) on hepatic apoptosis and the expressions of endothelial and inducible nitric oxide synthases (eNOS and iNOS) after liver ischemia/reperfusion (IR). Forty Wistar albino rats were randomly divided into five groups (n=8) as follows: sham group; IR group with ischemia/reperfusion alone; low-dose and high-dose TDF groups received 2.5 mg/kg and 10 mg/kg TDF, respectively; and PTX group received 40 mg/kg PTX. Blood was collected for the analysis of serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, uric acid, malondialdehyde (MDA), and total antioxidant capacity (TAC). MDA and TAC also were measured in liver tissue. Histopathological examination was performed to assess the severity of hepatic injury. Apoptosis was evaluated using the apoptosis protease-activating factor 1 (APAF-1) antibody; the expressions of eNOS and iNOS were also assessed by immunohistochemistry in all groups. Serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, uric acid, MDA, and TAC, tissue MDA and TAC levels, hepatic injury, and score for extent and for intensity of eNOS, iNOS, and apoptosis protease-activating factor 1 were significantly different in TDF and PTX groups compared to the IR group. High dose-TDF and PTX have the best protective effect on IR-induced liver tissue damage. This study showed that TDF and PTX supplementation may be helpful in preventing free oxygen radical damage, lipid peroxidation, hepatocyte necrosis, and apoptosis in liver IR injury and minimizing liver damage.

Phosphodiesterase 5 inhibition as a therapeutic target for ischemic stroke: A systematic review of preclinical studies

“…PDE5i have also shown to ameliorate ischemic damage in animal models of myocardial infarction (Koka et al, 2013, renal ischemia (Kucuk et al, 2012, Medeiros et al, 2010, Zahran et al, 2015, liver ischemia (Bektas et al, 2016), testicular torsion (Zavras et al, 2014, Yildiz et al, 2012, Erol et al, 2009, and ovarian ischemia (Arikan et al, 2010) through antiapoptotic and anti-oxidative stress mechanisms.…”

Effect of phosphodiesterase-5 inhibition on joint and muscle damage in rats with adjuvant arthritis

“…Tadalafil has a longer half-life, and greater selectivity for PDE5 than sildenafil (18). In a recent study by Bektas et al (18), tadalafil (10 mg/kg) prevented ROS damage, lipid peroxidation, hepatocyte necrosis, and apoptosis in rat liver ischemia/reperfusion injury and minimized liver damage. In a zymosan-induced rat model of arthritis, tadalafil (0.02-0.5 mg/kg, per oral) dose-dependently decreased neutrophil influx and tumor necrosis-alpha release into the synovial cavity (46).…”

“…Similarly, sildenafil citrate (5 mg/kg per day) for 3 days showed significant protection in a rat acetic acid-induced colitis model via its actions on oxidant/ antioxidant status (45). Tadalafil has a longer half-life, and greater selectivity for PDE5 than sildenafil (18). In a recent study by Bektas et al (18), tadalafil (10 mg/kg) prevented ROS damage, lipid peroxidation, hepatocyte necrosis, and apoptosis in rat liver ischemia/reperfusion injury and minimized liver damage.…”

Evaluation with endothelial nitric oxide synthase (eNOS) immunoreactivity of the protective role of astaxanthin on hepatorenal injury of remote organs caused by ischaemia reperfusion of the lower extremities

“…Several studies were conducted to show the eNOS activity following liver and kidney damage, because its decrease and imbalance with endothelin synthesis increase vascular resistance. Using tadalafil and pentoxifylline against liver I/R damage, Bektas et al [48] observed the prevention of oxidative stress, lipid peroxidation, and hepatocyte damage and thus reported a minimisation of endothelial damage. Potent eNOS activity was observed in the I/R group.…”