Acacetin Attenuates Renal Damage-Induced by Ischemia-Reperfusion with Declining Apoptosis and Oxidative Stress in Mice

Abstract

Background: Renal ischemia-reperfusion disturbs both the function and the histology of this organ. Acacetin (Aca) is a natural flavonoid that is effective for relief of many diseases. The aim of this study was to determine the impacts of Aca on renal ischemia-reperfusion process in mice.

Methods: In total, 84 male Balb/cmice divided into 12 groups and were administrated intraperitoneally for 4 days with or without surgery to dimethyl sulfoxide 0.01% or Aca (10, 25, and 50 mg/kg) as Control, control Acas, sham, sham Acas groups. Ischemia-reperfusion without or with Aca (10, 25, and 50 mg/kg) treatments were the other groups. Parameters related to the function and the histology of the kidneys were evaluated and statistically analyzed from kidney and blood serum samples in the respect of the groups.

Results: In ischemia-reperfusion and ischemia-reperfusion + Aca (10 mg/kg) groups, there were significantly increased in urea, creatinine, malondialdehyde (MDA), and apoptosis rate, whereas total antioxidant capacity decreased compared to the control and sham and ischemia-reperfusion + Aca (25 and 50 mg/kg) (P < 0.05). The histopathology alteration was seen in the ischemia-reperfusion group than the others (P < 0.01). Moreover, there was a significant difference between ischemia-reperfusion + Aca (25 and50 mg/kg) groups than ischemia-reperfusion + Aca (10 mg/kg) one (P < 0.05).

Conclusions: The recovery effect of Aca was offered on renal ischemia-reperfusion damage in a dose-dependent manner in mice, showing by kidney histopathology and functional criteria improvements. The attributed mechanism for this impression would be the antioxidant property of Aca, decreasing both MDA levels and apoptosis rate in kidney tissue.

Keywords: Acacetin; antioxidants; apoptosis; malondialdehyde; reperfusion injury.

Figure 1

Showing histological features in the kidney following ischemia-reperfusion and acacetin (Aca) (50 mg/kg) or both by H and E staining. In ischemia-reperfusion group, the yellow arrows in above picture and yellow stars in below picture show intra-tubular proteinaceous casts, whereas in below picture the yellow arrows depict tubular cell detachments, and arrow and star in blue demonstrate the shrinkage of renal glomerulus and tubular dilation, respectively (Above pictures are 100×, and below ones are 400 × captured, respectively). The originating sites of the glomerular vessels are shown by circles

Figure 2

Effect of ischemia- reperfusion (ISC) and Acacetin (Aca) or both on (a) malondialdehyde, (b) Total anti-oxidant capacity, (c) Apoptotic index in mice. *P < 0.05, **P < 0.01 compared to control and sham groups; a = P < 0.05, aa = P < 0.01 compared to Isc + Aca10 mg/kg group; b = P < 0.05, bb = P < 0.01 compared to Isc + Aca 25 mg/kg group; ≠≠: compared to ischemia-reperfusion group

Figure 3

Apoptosis induction in the kidney followed by ischemia-reperfusion and acacetin (Aca) (50 mg/kg) or both by TUNEL staining (×400); Aca = acacetin. The yellow arrows referred to the emerald green nuclei of apoptotic cells. The left pictures are stained cytoplasm, the middle figures show stained nuclei, and the right ones are the merges