| Summary: | 博士 === 國立陽明大學 === 臨床醫學研究所 === 107 === Iodinated radiocontrast is widely used in medical image surveys such as computer tomography scans and intravenous pyelography. Invasive procedures such as coronary angiograms or neurovascular angiography also utilize radiocontrast for the identification of lesions and further treatment. Radiocontrast is generally safe in subjects with normal renal function. However, the risk of nephrotoxicity is high when it is used in elderly patients or those with previous renal function impairment. Contrast-induced nephropathy (CIN) accounts for 10% of the causes of acute kidney injury in hospitals, and the incidence as high as 50% in patients with cardiovascular disease, diabetes mellitus, or preexisting chronic kidney disease. Different preventive measures such as using hydration, sodium bicarbonate, and N-acetylcysteine have been developed to reduce the incidence of CIN but the results were not satisfactory until recently.
Resveratrol (3,5,4’-trihydroxystilbene) is a natural polyphenol found in grapes and red wine. Previous investigations reported it possesses anti-inflammatory effects. Resveratrol can activate the mammalian sirtuin Sirt1. Mammalian Sirt1 deacetylates a host of target proteins that are important for apoptosis, the cell cycle, circadian rhythms, mitochondrial function, and metabolism. Administration of resveratrol can exert a cytoprotective effect and prevent kidney disease, cardiovascular disease, and cancer through Sirt1. The severity of diabetic nephropathy can be attenuated by resveratrol through anti-oxidative and anti-inflammatory effects. Previous animal studies reported that resveratrol can ameliorate chronic kidney disease and acute kidney injury, and it was also shown to decrease the inflammatory cells in the kidney, such as polymorphonuclear granulocytes, in acute kidney injury models in previous work.
Studies on inflammasomes have recently shifted from infectious causes to non-infectious causes. Acute kidney injury has been shown to involve inflammasomes. Free radicals and reactive oxygen species can activate the inflammasome pathway, particularly NLRP3. Studies such as rhabdomyolysis-induced acute kidney injury are involved in the inflammasome pathway. Our study also explored the effects of inflammasomes caused by contrast nephropathy and the protective effects of resveratrol.
The aim of this study was to investigate the protective effect of resveratrol in a rat model of CIN. Sprague-Dawley rats were divided into four groups: a control group (0.9% saline infusion only), a resveratrol group (RSV, resveratrol, 30 mg/kg), a contrast media group (CIN), and a resveratrol + contrast media group (RCIN, resveratrol 30 mg/kg 60 min before CIN). CIN was induced via the intravenous injection of a single dose of indomethacin (10 mg/kg), one dose of N-nitro-L-arginine methyl ester (10 mg/kg), and a single dose of contrast medium iopromide (2 g/kg). Blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were higher in the CIN group than in the other groups. The histopathological tubule injury scores were also higher in the CIN group than in the other groups (p < 0.01). NLPR3 in the kidney tissue was higher in the CIN group than in the other groups; however, these results were improved by resveratrol in the RCIN group compared with the CIN group. The expressions of IL-1β and the percentage of apoptotic cells were higher in the CIN group than in the control and RSV groups, but they were lower in the RCIN group than in the CIN group. The expression of cleaved caspase-3 was higher in the CIN group than in the control and RSV groups, but lower in the RCIN group than in the CIN group. Resveratrol treatment attenuated both injury processes and apoptosis and inhibited the inflammasome pathway in the rat CIN model.
Our results demonstrate that resveratrol can inhibit apoptosis and inflammasome expression induced in a CIN model. Previous studies showed that resveratrol can suppress NLRP3 and subsequent IL-1β in sepsis models. Hence, the regulation of NLRP3 inflammasome in our acute kidney injury model conferred protection from subsequent kidney injury. These findings may be helpful when developing renoprotective drugs before the use of contrast medium.
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