Abstract
BackgroundAcute kidney injury (AKI) still remains an unresolved problem in pharmacotherapy and renal inflammation is a major factor in its development. Chloroquine, a well-known antimalarial drug, posses pleitropic effects as well: antiinflammatory, anticoagulant and vascular actions. The effects of chloroquine on renal function may involve significant increase in urine flow rate, glomerular filtration rate and sodium excretion, as well as stimulation of nitric oxide synthase. However, its role in experimental models of renal I/R injury is unknown. We aimed to analyze the acute effects of a single-dose intravenous chloroquine administered at three different times in the experimental model of I/R injury in rat.MethodsRats were subjected to bilateral renal ischemia (45 min) followed by reperfusion with saline lasting 4 hours. Chloroquine was administered in doses of 0.3 mg/kg i.v. and 3 mg/kg i.v. 30 min before ischemia, 30 min before reperfusion and 5 min before reperfusion. Selected a hemodynamic, biochemical and morphological parameters were followed in the Sham-operated animals and rats subjected to I/R injury and pretreated with saline or chloroquine.ResultsChloroquine (0.3 and 3 mg/kg, i.v.) protected the I/R injured kidney in an U-shaped manner. Both doses were protective regarding biochemical and histological markers of the I/R injury (serum urea, creatinine and fractional excretion of sodium, as well as total histological score, tubular necrosis score and KIM-1 staining score) (P<0.05 vs. corresponding controls, i.e. rats subjected to I/R injury and treated with saline only). The protective effects of the lower dose of chloroquine were more profound. Time-related differences between pretreatments were not observed (P>0.05, all).ConclusionOur study shows for the first time that a single dose of chloroquine (0.3 mg/kg i.v.) could afford significant protection of the injured rat kidney.
Highlights
Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), is a heterogeneous process, that is usually classified into three different groups: (a) prerenal, which is an adaptive mechanism of severe renal damage, (b) intrinsic, which is structural renal injury and (c) postrenal, which represents mechanical obstruction of the urinary system
Our study shows for the first time that a single dose of chloroquine (0.3 mg/kg i.v.) could afford significant protection of the injured rat kidney
It is important to notice that protective effects of chloroquine in the present experimental model of I/R injury is not time-dependant, and the drug could be administered immediately before reperfusion
Summary
Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), is a heterogeneous process, that is usually classified into three different groups: (a) prerenal, which is an adaptive mechanism of severe renal damage (hypovolemia and/or hypotension), (b) intrinsic, which is structural renal injury and (c) postrenal, which represents mechanical obstruction of the urinary system. Renal ischemia-reperfusion (I/R) injury is one of the most common causes of prerenal AKI [1]. I/R injury remains an unresolved problem in pharmacotherapy with high mortality rate, especially in critically ill patients. The important role of inflammation in the development of renal ischemia-reperfusion injury is confirmed in many studies [3,4]. Acute kidney injury (AKI) still remains an unresolved problem in pharmacotherapy and renal inflammation is a major factor in its development. Its role in experimental models of renal I/R injury is unknown. We aimed to analyze the acute effects of a singledose intravenous chloroquine administered at three different times in the experimental model of I/R injury in rat
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