Ameliorative effect of rosiglitazone, a peroxisome proliferator gamma agonist on adriamycin‐induced cardio toxicity via suppressing oxidative stress and apoptosis

Abstract

We investigated the rosiglitazone (RSG) effect on adriamycin (ADM)‐induced cardio toxicity in experimental animals. Forty adult Wistar male rats were separated into four groups as follows: normal control; RSG (10 mg/kg)‐treated; ADM (10 mg/kg)‐administered; and ADM (10 mg/kg) + RSG (10 mg/kg)‐treated. Serum lipid level, different biochemical biomarkers, histological analysis, and nuclear factor erythroid 2‐related factor/heme oxygenase‐1 (Nrf2/HO‐1), Caspase 3, B‐cell lymphoma 2 (Bcl‐2), and Bax gene expression were assessed in serum and cardiac tissue samples. Our results show that RSG treatment in ADM‐administered animals significantly diminished low‐density lipoprotein cholesterol, triglyceride, and total cholesterol, and increases high‐density lipoprotein cholesterol (HDL‐c) in comparison with the ADM group. RSG treatment reduced the effect of ADM administration on cardiac dysfunction markers such as cardiac troponin T Creatine Kinase‐MB, aspartate aminotransferase, and lactate dehydrogenase, showing the amelioration of cardio toxicity in ADM‐administered rats. Additionally, RSG treatment significantly decreased the level of malondialdehyde and nitric oxide in cardiovascular tissue. RSG‐treated rats in combination with ADM likewise showed a significant increase in reduced glutathione, superoxide dismutase, catalase content, and the activity of glutathione peroxidase (GPx) as compared with ADM group. Moreover, RSG treatment in ADM rats significantly increased an Nrf2 and HO‐1 expression in comparison with ADM group. While in apoptosis parameters, RSG treatment in ADM rats significantly diminished a cleaved caspase‐3 and Bax expression as well as expanded Bcl‐2 expression when contrasted with ADM group of rats. In conclusion, RSG is capable of protecting heart toxicity in ADM‐treated animals through defensive effects on oxidative stress and biochemical markers.

Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis

“…Rosiglitazone and pioglitazone belong to the thiazolidinedione class of hypoglycemic agents and are recognized as PPAR-γ agonists. These two drugs were not only able to enrich GSH contents and GPX activity and defend the heart against oxidative stress but also prevented DOX or I/R-induced myocardial injury [214][215][216][217]. Some clinical studies have shown that pioglitazone treatment (30 mg/day, P.O for 4 weeks) exhibits antioxidant properties in diabetic patients, as reflected by a decrease in MDA [218,219].…”

Rosiglitazone inhibits acyl‐CoA synthetase long‐chain family number 4 and improves secondary brain injury in a rat model of surgical brain injury

“…Ferroptosis has been reported to be associated with damage to the brain and heart. 15,16 Thiazolidinediones appear to work preventively rather than therapeutically, under this condition, we injected rosiglitazone into the abdominal cavity 30 min before the operation, 30 min after the operation and 4 h after the operation, thus allowing sufficient time for proper phospholipid remodelling. The results showed that intraperitoneal injection of rosiglitazone reduced brain edema and ROS accumulation in SBI rats (Figure 2C).…”

Nrf2: a dark horse in doxorubicin-induced cardiotoxicity

“…Acute phase proteins orosomucoid 1 and follistatin-like 1 reduce the adhesion of Nrf2 to Keap1 in doxorubicin-induced cardiomyocytes, thereby promoting the nuclear translocation of Nrf2 and reducing the excessive accumulation of ROS in cardiomyocytes, thereby exerting antioxidant and anti-apoptotic effects [ 28 , 79 , 125 , 128 , 192 – 195 ]. Numerous other agonists and inhibitors, such as lipocalin agonists and phosphatase inhibitors, have been demonstrated in the available literature to promote doxorubicin-induced nuclear expression of Nrf2 in cardiomyocytes, thereby reducing the generation of oxidative stress in cardiomyocytes to reduce damage to the mitochondrial membrane of cardiomyocytes and thereby ameliorating apoptosis and oxidative stress in cardiomyocytes [ 14 , 31 , 196 , 197 ].…”