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. 2014 Nov 15;7(12):8391-400.
eCollection 2014.

Panax Notoginseng Saponins Attenuates Cisplatin-Induced Nephrotoxicity via Inhibiting the Mitochondrial Pathway of Apoptosis

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Free PMC article

Panax Notoginseng Saponins Attenuates Cisplatin-Induced Nephrotoxicity via Inhibiting the Mitochondrial Pathway of Apoptosis

Xinwen Liu et al. Int J Clin Exp Pathol. .
Free PMC article

Abstract

The goal of this experiment was to investigate the protective effect and the molecular mechanism of Panax Notoginseng Saponins (PNS) on cisplatin-induced nephrotoxicity through mitochondrial pathway of apoptosis. The rats underwent intraperitoneal injection with a single dose of cisplatin, a subset of rats were also intraperitoneally injected with 31.35 mg/kg PNS once a day for 8 days. At day 1, 4 and 8 after exposure to cisplatin, the concentrations of blood urea nitrogen (BUN), serum creatinine (Scr) and urinary N-acetyl-β-D-Glucosaminidase (NAG) were determined using commercial kits. The pathological change of renal tissue were examined using H & E staining and transmission electron microscopy. The rate of apoptosis and the expression of Bcl-2 in rat renal tissue were detected by using TUNEL staining and Western bloting, respectively. And the expressions of Bax and caspases 9 were detected by immunnohistochemistry. The results showed that PNS significantly protected against cisplatin-induced nephrotoxicity, as evidenced by the decrease in concentration of blood BUN, Scr and urinary NAG, as well as the attenuation of renal histopathological damage. Furthermore, PNS reduced the rate of apoptosis, and the mechanism studies showed that PNS inhibited the expression of Bax and caspase 9, while increased the expression of Bcl-2. This study first demonstrated that PNS can protect against cisplatin-induced nephrotoxicity and reduce renal tissue apoptosis via inhibiting the mitochondrial pathway.

Keywords: Panax notoginseng saponins (pns); apoptosis; cisplatin; mitochondrial pathway.

Figures

Figure 1
Figure 1
The effects of PNS on the levels of Serum Cr, BUN and urine NAG. The results are presented as the means ± SE. *P < 0.01 when compared with the control group, #P < 0.01 when compared with the cisplatin-only group.
Figure 2
Figure 2
Histomorphological examination of rat renal tissue (H & E staining, 400×). A, D, G: The control group at day 1, 4 and 8; B, E, H: The cisplatin-only group at day 1, 4 and 8; C, F, I: The cisplatin-PNS group at day 1, 4 and 8.
Figure 3
Figure 3
The effects of PNS on the mitochondrial of renal tubular epithelial cells. A, D, G: The control group at day 1, 4 and 8, the structure and shape of renal tubular epithelial cells were normal; B, E, H: The cisplatin-only group at day 1, 4 and 8, the mitochondrial were swelling, mitochondrial cristae were vague, rupture and melted; C, F, I: The cisplatin-PNS group at day 1, 4 and 8, the mitochondrial injury was improved.
Figure 4
Figure 4
The effect of PNS on the apoptosis rate of rat renal tissue detected using TUNEL staining. A, D, G: The control group at day 1, 4 and 8; B, E, H: The cisplatin-only group at day 1, 4 and 8; C, F, I: The cisplatin-PNS group at day 1, 4 and 8. *P < 0.01 when compared with the control group, #P < 0.01 when compared with the cisplatin-only group.
Figure 5
Figure 5
The effects of PNS on the expression of caspase9 detected using immunohistochemical method. A, D, G: Normal control group at 1, 4 and 8 d; B, E, H: Cisplatin-only group at day 1, 4 and 8; C, F, I: Cisplatin-PNS group at day 1, 4 and 8. The results are presented as the means ± SE. *P < 0.01 when compared with the control group, #P < 0.01 when compared with the cisplatin-only group.
Figure 6
Figure 6
The effects of PNS on the expression of Bax and caspase9 in rat renal tissue detected using immunohistochemical method. A, D, G: The control group at day 1, 4 and 8; B, E, H: The cisplatin-only group at day 1, 4 and 8; C, F, I: The cisplatin-PNS group at day 1, 4 and 8. The results are presented as the means ± SE. *P < 0.01 when compared with the control group, #P < 0.01 when compared with the cisplatin-only group.
Figure 7
Figure 7
The effect of PNS on the expression of Bcl-2 in rat renal tissue detected by WB. A: The control group; B: The cisplatin-only group; C: The cisplatin + PNS group. The results are presented as the means ± SE. *P< 0.01 when compared with the control group, #P < 0.01 when compared with the cisplatin-only group.

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