Silibinin nephroprotective effects in renal ischemia reperfusion injury in rats via regulation of Notch-1.
Aim: To evaluate nephroprotective effects of Silibinin in renal ischemia -reperfusion injury in rats by regulation of Notch-1 and Jagged-1.
Materials and Methods: 28 male Wistar albino rats were randomly divided into four groups, (seven rats / group): sham group (laparotomy only), control group (ischemia for 30 min / 2 hrs reperfusion), DMSO vehicle group (rats were injected intraperitoneally with 10% DMSO 1 hour before ischemia, then ischemia for 30 min / 2 hrs reperfusion, Silibinin treatment group (rats were injected with Silibinin (60 mg/kg) intraperitoneally 1 hour before ischemia, then "ischemia for 30 min / 2 hrs reperfusion. The kidneys were harvested after 2 hours of reperfusion for assessment of kidney injury molecule-1 (KIM-1), interleukin 1 β (IL-1β), TNF-α, F2-Isoprostane, and glutathione (GSH) by ELISA technique; Notch-1 and Jagged-1 mRNA levels were assessed by reverse transcription-polymerase chain reaction (RT-PCR), BAX and Bcl2 protein expression were assessed by immunohistochemistry (IHC).
Results: Silibinin demonstrated considerable amelioration of renal ischemia reperfusion injury as evidenced by the significant reduction of KIM-1, IL-1β, TNF α, F2-Isoprostane, in rat kidneys pretreated with Silibinin, GSH level was significantly elevated in rat kidneys pretreated with silibinin. Furthermore silibinin pretreatment significantly reduced Notch-1 and Jagged-1 mRNA expression after renal ischemia reperfusion.
Conclusions: Silibinin offers protection against renal ischemia reperfusion injury due to its antioxidant, anti-inflammatory, and anti-apoptotic effects, those effects are associated with the downregulation of Notch-1 and its ligand, Jagged-1.
Materials and Methods: 28 male Wistar albino rats were randomly divided into four groups, (seven rats / group): sham group (laparotomy only), control group (ischemia for 30 min / 2 hrs reperfusion), DMSO vehicle group (rats were injected intraperitoneally with 10% DMSO 1 hour before ischemia, then ischemia for 30 min / 2 hrs reperfusion, Silibinin treatment group (rats were injected with Silibinin (60 mg/kg) intraperitoneally 1 hour before ischemia, then "ischemia for 30 min / 2 hrs reperfusion. The kidneys were harvested after 2 hours of reperfusion for assessment of kidney injury molecule-1 (KIM-1), interleukin 1 β (IL-1β), TNF-α, F2-Isoprostane, and glutathione (GSH) by ELISA technique; Notch-1 and Jagged-1 mRNA levels were assessed by reverse transcription-polymerase chain reaction (RT-PCR), BAX and Bcl2 protein expression were assessed by immunohistochemistry (IHC).
Results: Silibinin demonstrated considerable amelioration of renal ischemia reperfusion injury as evidenced by the significant reduction of KIM-1, IL-1β, TNF α, F2-Isoprostane, in rat kidneys pretreated with Silibinin, GSH level was significantly elevated in rat kidneys pretreated with silibinin. Furthermore silibinin pretreatment significantly reduced Notch-1 and Jagged-1 mRNA expression after renal ischemia reperfusion.
Conclusions: Silibinin offers protection against renal ischemia reperfusion injury due to its antioxidant, anti-inflammatory, and anti-apoptotic effects, those effects are associated with the downregulation of Notch-1 and its ligand, Jagged-1.