Effects of apigenin on the expression levels of B‑cell lymphoma‑2, Fas and Fas ligand in renal ischemia‑reperfusion injury in rats

Abstract

The aim of the present study was to investigate the effect and possible mechanism of apigenin on renal ischemia-reperfusion (I/R) injury in rats, as well as in in vitro experiments. In total, 36 rats were subjected to 45 min of renal ischemia, with or without treatment prior to ischemia with different concentrations of apigenin (2, 10 and 50 mg/kg) administered intravenously. All rats were sacrificed at 24 h after I/R injury. The serum creatinine (Cr) and blood urea nitrogen (BUN) levels were analyzed, and histological examination was conducted. In addition, the expression levels of B-cell lymphoma 2 (Bcl-2) and Fas/Fas ligand (FasL) were detected by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. For in vitro experiments, the NRK-52E cell line was employed. The viability, apoptosis and expression levels of Fas, FasL and Bcl-2 were examined in the culture of NRK-52E cells following the I/R. The results indicated that apigenin significantly decreased the levels of serum Cr and BUN induced by renal I/R, demonstrating an improvement in renal function. The histological evidence of renal damage associated with I/R was also mitigated by apigenin in vivo. Furthermore, apigenin increased the cell viability and decreased cell apoptosis in the culture of NRK52E after I/R in vitro. Compared with the I/R group, the expression of Bcl-2 was upregulated and the expression levels of Fas and FasL were downregulated by apigenin at the mRNA and protein levels in vivo and in vitro. In conclusion, apigenin appeared to increase the expression of Bcl-2 and reduce Fas/FasL expression in renal I/R injury, providing evident protection against renal I/R injury in rats.

Maternal oxidized soybean oil exposure in rats during lactation damages offspring kidneys via Nrf2/HO‐1 and NF‐κB signaling pathway

“…We also found that the mRNA expression levels of the Fas and Fasl genes in the OSO group were upregulated. Our data are consistent with those of Liu et al ., 61 who reported that increased Fas / Fasl expression could cause kidney damage in rats. In addition, the caspase gene family is essential in maintaining homeostasis by regulating the occurrence of cell death and inflammation.…”

Protective Effects and Mechanisms of Flavonoids in Renal Ischemia-Reperfusion Injury

“…PI3K/Akt signaling pathway regulates renal repair after I/R injury, and apigenin (20 mg/kg) pretreatment has been shown to protect against renal I/R injury and prevent tubular apoptosis in vitro and in vivo by activating PI3K/Akt-mediated mitochondria-dependent apoptotic signaling pathway [61]. In addition, inhibition of renal apoptosis by suppressing the activation of the Fas/FasL pathway may be another protective mechanism of apigenin against renal I/R injury [62]. Furthermore, genistein (15 mg/kg) was shown to exert its antiapoptotic and proliferative effects via the SIRT1/p53 axis, and thus ameliorates I/R-induced renal injury [6].…”

Protective Effects of Yiqi Xingnao Oral Liquid on Cerebral Ischemia‐Reperfusion Injury in Rats and Its Related Mechanisms

“…Bcl-2, an antiapoptotic protein, is an important factor in determining whether apoptosis occurs and the severity of apoptosis [29,30]. A study by Liu et al [31] In addition, VEGF, an effective trigger of angiogenesis, can change the microcirculation and improve survival and regeneration of neurocytes through angiogenesis in ischemic tissues [33]. Increasing evidence has shown that the combination of VEGF and its receptors can trigger multiple downstream signals and promote angiogenesis [34,35].…”

“…Bcl-2, an antiapoptotic protein, is an important factor in determining whether apoptosis occurs and the severity of apoptosis [ 29 , 30 ]. A study by Liu et al [ 31 ] indicated that apigenin could inhibit cell apoptosis by increasing the expression level of Bcl-2, thus protecting renal I/R injury. Another study also showed that Radix Ilicis Pubescentis total flavonoids could alleviate cerebral I/R injury via increasing the Bcl-2 protein expression and enhancing the antiapoptotic ability of neurocytes [ 32 ].…”