Angiotensin antagonists and renal ischemia/reperfusion: Possible modulation by l-carnitine

Abstract

Introduction: Ischemia/reperfusion (I/R) injury and therapy with angiotensin antagonists were shown to exert significant effects on the kidney. The study aimed to investigate the protective effect, if any, of l-carnitine on the initial nephrotoxic effects of ramipril or losartan on I/R insult in rats. Methods: I/R was induced through bilateral renal ischemia for 60 min followed by 60 min of reperfusion. Groups I and II received both 1% Tween 80 p.o. and saline i.p. and served as sham-operated and I/R control groups, respectively. Groups III–VII received 2 weeks pretreatment with ramipril (1 mg/kg; p.o.), losartan (10 mg/kg; i.p.), l-carnitine (200 mg/kg; i.p.) and l-carnitine plus either ramipril or losartan, respectively. Chosen markers included kidney function tests, oxidative stress and inflammatory biomarkers as well as histological assessment of kidney sections. Results: I/R increased plasma creatinine and urea levels but decreased albumin level; meanwhile, it increased the kidney tumor necrosis factor-alpha (TNF-α) content, myeloperoxidase (MPO) and plasma lactate dehydrogenase (LDH) activities. Moreover, I/R decreased kidney carnitine, glutathione, and total nitrate/nitrite contents as well as superoxide dismutase activity. Both ramipril and losartan elevated creatinine and urea levels; meanwhile, they lowered raised LDH, TNF-α and MPO as compared to I/R-control group. l-carnitine alone or combined with either agent decreased creatinine and urea levels, LDH and MPO activities as well as TNF-α content as compared to ramipril or losartan monotherapy. Conclusions: l-carnitine can protect the kidney from the initial deleterious effects of either ramipril or losartan in rats subjected to I/R most probably by virtue of its antioxidant and anti-inflammatory effects.

Keywords

• l-carnitine
• Ischemia/reperfusion
• Losartan
• Oxidative stress
• Ramipril