Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

Abstract

It was demonstrated that fenofibrate and telmisartan exerted renoprotective effects in ischemia/reperfusion (I/R) injury. Because the combination of fenofibrate and telmisartan synergistically enhanced peroxisome proliferator-activated receptor (PPAR) activation, we hypothesized that the combination of both drugs may exert prolonged beneficial effects in renal I/R injury than fenofibrate alone. Forty-eight male Wistar albino rats were divided into eight groups. Hyperlipidemia was induced by cholesterol feeding for 4 weeks. At the end of the fourth week, renal I/R injury was performed by occlusion of both renal vascular pedicles for 60 minutes, followed by 24 hours of reperfusion. In the treatment group, fenofibrate alone and in combination with telmisartan was administered 2 weeks prior to renal ischemia. At the end of the experiment, blood and kidneys were isolated for biochemical and histological analysis. I/R in hyperlipidemic rat shows significantly increased lipid peroxidation, nitric oxide, and myeloperoxidase activity, and depletion of antioxidant enzyme compared with control rats, and that was significantly restored after fenofibrate and telmisartan treatment. Also, significant increases in serum homocysteine level were detected following I/R. Fenofibrate treatment further elevated homocysteine level, which was reduced by telmisartan in combination with fenofibrate. The most significant histological damage was found in the hyperlipidemic rat subjected to renal I/R, which was reduced significantly with combination therapy. The results of this study concluded that fenofibrate alone and in combination with telmisartan significantly ameliorated renal I/R injury. The additive beneficial effect of telmisartan is predicted to reduce homocysteine-induced oxidative stress through reduced nitric oxide production during I/R.

Effects of captopril, telmisartan and bardoxolone methyl (CDDO‐Me) in ischemia‐reperfusion‐induced acute kidney injury in rats: an experimental comparative study

“…CAP, TEL and BM increased eNOS levels and decreased NO, iNOS and ET‐1 levels. In agreement with the present results, previous studies demonstrated that pretreatment with TEL, CAP and BM significantly decreased NO levels and expression of iNOS and ET‐1 . Consequently, the results of this study suggest that CAP, TEL and BM may decrease NO levels by inhibiting iNOS activity and increase NO bioavailability by inducing eNOS activity.…”

“…In the current study, IR caused significant increases in the levels of urea, creatinine, NGAL and oxidative stress markers, as well as significant decreases in the activities of antioxidant enzymes and TT levels, which was accompanied by renal damage. However, all drugs used in the study reduced levels of urea, creatinine and NGAL, increased SOD activity and GSH‐Px activity and ameliorated histopathologic renal damage, consistent with previous studies . The major new finding of this study is that CAP, TEL and BM decreased TOS and OSI levels, whereas they increased TAS and TT levels.…”

RETRACTED ARTICLE: Effect of preischemic treatment with fenofibrate, a peroxisome proliferator-activated receptor-α ligand, on hepatic ischemia–reperfusion injury in rats

“…The PPARa agonist, fenofibrate, supports multiple cellular functions and plays a key role in the protection from oxidative stress induced injury (Gelosa et al 2010;Hou et al 2010). So, fenofibrate exerts an antioxidant, anti-inflammatory and anti-ischemic protective effect on the brain (Chen et al 2007) and kidney (Bhalodia et al 2010).…”

Immunological study of expression of CD1 in preimplantation and midgestation mouse embryo cells and placental trophoblasts and the role of decidual natural killer T cells at the feto–maternal interface

“…It exerts its primary effects on lipid metabolism by the activation of PPAR-a by fenofibric acid, the active moiety in plasma. Furthermore, fenofibrate exerts an antioxidant, anti-inflammatory, and anti-ischemic protective effect on the heart [9], intestine [10], brain [11], and kidney [12]. It also improves insulin sensitivity and protects against microvascular events in patients with diabetes [8].…”