Panax notoginseng saponins attenuates cisplatin-induced nephrotoxicity via inhibiting the mitochondrial pathway of apoptosis

Int J Clin Exp Pathol. 2014 Nov 15;7(12):8391-400. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cisplatin / toxicity*
  • Disease Models, Animal
  • In Situ Nick-End Labeling
  • Kidney / drug effects*
  • Kidney / pathology
  • Male
  • Microscopy, Electron, Transmission
  • Mitochondria / drug effects
  • Panax notoginseng / chemistry*
  • Peripheral Nervous System Diseases / chemically induced
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / pharmacology*

Substances

  • Antineoplastic Agents
  • Saponins
  • Cisplatin