Pitavastatin Attenuates Leukocyte-Endothelial Interactions Induced by Ischemia-Reperfusion Injury in the Rat Retina

Abstract

Pitavastatin effectively attenuated ischemia-induced leukocyte-endothelial interactions in the rat retina.

Pitavastatin subacutely improves endothelial function and reduces inflammatory cytokines and chemokines in patients with hypercholesterolaemia

“…In many reports on experimental19 20 and clinical populations, pitavastatin improved endothelial function through upregulated endothelial nitric oxide synthase activity. In addition, data from previous reports support the suggestion that pitavastatin treatment reduces the levels of cytokines and chemokines 5 21 22. The relatively quick pleiotropic action of pitavastatin seen in this study is also consistent with observations from a previous study, in which a 2-week course of pitavastatin resulted in improved FMD in patients with hypercholesterolaemia 21 23 24.…”

In Vivo Cardioprotection by Pitavastatin From Ischemic-reperfusion Injury Through Suppression of IKK/NF-κB and Upregulation of pAkt–e-NOS

“…1,2,11,23 On the other hand, pitavastatin attenuated oxidative stress and TBARS, which could be due to the suppression of IKK/NF-kB, thereby reduced ROS production and/or amplification of myocardial antioxidant defense system such as CAT, SOD, GSH, and GSHPx in ischemic-reperfused heart, which scavenges ROS and lipid peroxyl radicals, and prevents myocardial damage. 1,2,[6][7][8][9]21 In this study, we observed a significant downregulation of activated phosphorylated forms of Akt and e-NOS in ischemic-reperfused heart, which were upregulated by pitavastatin treatment. It is well established that NO is a key regulator of myocardial function under physiological conditions, 24,25 and its production is regulated by e-NOS activation, which is mainly arbitrated through a phosphorylation-dependent mechanism involving the serine/threonine kinase pAkt.…”

“…10,11 We speculated that the enhanced expression of pAkt, (p) e-NOS and suppression of TNF-a, IKK/NF-kB by pitavastatin negatively regulate the dysregulated production of Bcl-2, Bax, and caspase-3 proteins and attenuates the stimulus-dependent activation of apoptosis and myocytes damage in response to IR. [7][8][9] In our study, to ensure that pitavastatin prevents the myocardial damage caused by IR, serum CK-MB and myocardial (2): absence of any myonecrosis, edema, and inflammation; score (+): focal areas of myonecrosis, edema, and inflammation; score (++): patchy areas of myonecrosis, edema, and inflammation; score (+++): confluent areas of myonecrosis, edema, and inflammation; score (++++): massive areas of myonecrosis, edema, and inflammation. LDH levels were assessed.…”

“…It has been reported that pitavastatin inhibits the production of reactive oxygen species (ROS) and inhibits leukocyteendothelial interactions, thereby attenuating oxidative stress, inflammation, and organ damage. 6,7 Furthermore, pitavastatin improved cardiac performance and remodeling in failing rat hearts by the upregulation of pAkt, endothelial nitric oxide synthase (e-NOS), and inhibition of nuclear factorkappa B (NF-kB). 8,9 Accordingly, we hypothesized that pitavastatin may ameliorate ischemia-reperfusion (IR)-induced MI in rats, which has not been evaluated so far.…”

Evaluation of Leukocyte-Endothelial Interactions in Retinal Diseases

“…On the basis of the results of these experiments, many investigators have studied various agents that can attenuate tissue damage by suppressing leukocyte-endothelial interactions in the postischemic retina. Antithrombin III [83,84], tacrolimus (FK506) [85], argatroban (direct thrombin inhibitor) [86], statin [87,88], Rho-associated protein kinase inhibitor [89], superoxide dismutase [90], thalidomide [91], selectin ligands/inhibitor (SKK-60060) [92], triamcinolone acetonide [93], ischemic preconditioning [94,95], platelet depression [81], and 17β-estradiol [96] are reported to reduce leukocyte accumulation in the postischemic retina and thereby reduce neural damage.…”