Candesartan ameliorates acute myocardial infarction in rats through inducible nitric oxide synthase, nuclear factor-κB, monocyte chemoattractant protein-1, activator protein-1 and restoration of heat shock protein 72

Abstract

Candesartan, an angiotensin II type 1 receptor antagonist, has a variety of biological activities, including antioxidant, anti‑inflammatory and anticancer activities, with specific pharmacological effects. The present study investigated the mechanisms and protective effect of candesartan on acute myocardial infarction in rats. Male Wistar rats (8‑week‑old) were induced as a model of acute myocardial infarction and treated with candesartan (0.25 mg/kg) for 2 weeks. The present study first measured the activities of casein kinase (CK), the MB isoenzyme of creatine kinase (CK‑MB) and lactate dehydrogenase (LDH), the level of cardiac troponin T (cTnT) and infarct size. Subsequently, western blot analysis was performed to analyze the protein expression levels of inducible nitric oxide synthase (iNOS) and heat shock protein 72 (HSP72) in the rats. An enzyme linked immunosorbent assay was used to detect iNOS and nuclear factor‑κB (NF‑κB) activity. In addition, gene expression levels of monocyte chemotactic protein‑1 (MCP‑1) and activating protein‑1 (AP‑1) were determined using reverse transcription‑quantitative polymerase chain reaction analysis. Finally, the activities of caspase‑3 and caspase‑9 were examined using colorimetric assay kits. In the serum of the rat model of acute myocardial infarction, candesartan significantly increased the activities of CK, CK‑MB and LDH, and the level of cTnT. The infarction size was perfected by candesartan treatment. Candesartan significantly reduced the protein expression and activity of iNOS, the activity of NF‑κB p65, and the gene expression levels of MCP‑1 and AP‑1 in the rat model of acute myocardial infarction. Candesartan increased the protein expression of HSP‑72 in the acute myocardial infarction rat model. However, candesartan did not effect the levels of caspase‑3 or caspase‑9 in the rat model of acute myocardial infarction. These results suggested that candesartan ameliorates acute myocardial infarction in rats through iNOS, NF‑κB, MCP‑1 and AP‑1, and the restoration of HSP72.

Candesartan Attenuates Cisplatin-Induced Lung Injury by Modulating Oxidative Stress, Inflammation, and TLR-4/NF-κB, JAK1/STAT3, and Nrf2/HO-1 Signaling

“…Oxidative stress and injurious inflammatory responses have been implicated in CIS toxicity [ 7 , 40 ]. The Ang II AT1R blocker CAN showed beneficial effects against inflammation and stress in cardiovascular, neurovascular, and other diseases [ 34 , 35 , 38 , 39 ]. Herein, we investigated the protective effect of CAN against oxidative stress, inflammation, and lung injury induced by CIS in rats, emphasizing the role of TLR4/NF-κB, JAK1/STAT3, PPARγ, and Nrf2/HO-1 signaling.…”

“…The RAS is involved in inflammatory disorders and a significant interest in mitigating inflammation by drugs modulating this system has recently emerged [ 33 ]. In this context, Ang II AT1R blockers (ARBs) showed protective effects against inflammation, apoptosis, and endoplasmic reticulum (ER) stress in different experimental models [ 34 , 35 , 36 , 37 ]. Candesartan (CAN) is a highly selective Ang II AT1R blocker that showed beneficial effects against oxidative injury and inflammation [ 34 , 35 ].…”

“…In this context, Ang II AT1R blockers (ARBs) showed protective effects against inflammation, apoptosis, and endoplasmic reticulum (ER) stress in different experimental models [ 34 , 35 , 36 , 37 ]. Candesartan (CAN) is a highly selective Ang II AT1R blocker that showed beneficial effects against oxidative injury and inflammation [ 34 , 35 ]. CAN attenuated inflammation by inhibiting NF-κB activation and protected against stroke-induced neuronal damage [ 38 ], hypertension in pregnancy [ 39 ], and acute myocardial infarction (AMI) [ 35 ].…”

“…Candesartan (CAN) is a highly selective Ang II AT1R blocker that showed beneficial effects against oxidative injury and inflammation [ 34 , 35 ]. CAN attenuated inflammation by inhibiting NF-κB activation and protected against stroke-induced neuronal damage [ 38 ], hypertension in pregnancy [ 39 ], and acute myocardial infarction (AMI) [ 35 ]. Despite the reported pharmacological effects of CAN, its ability to mitigate CIS-induced lung injury has not been reported yet.…”

Candesartan and epigallocatechin‐3‐gallate ameliorate gentamicin‐induced renal damage in rats through p38‐MAPK and NF‐κB pathways

“…It has been proposed that blocking of angiotensin receptors by angiotensin receptor blockers (ARBs) may induce a defensive mechanism regarding drug‐induced nephrotoxicity . Candesartan, a highly selective angiotensin II type I receptor blocker, is suggested to have potent antioxidant and anti‐inflammatory actions in investigational models of chronic pancreatitis, myocardial infarction, and cerebral ischemia, and it may also be utilized to protect against drug‐induced nephrotoxicity . It was established that candesartan suppresses renal inflammation by a direct antioxidant effect independent of its antihypertensive effect.…”