Complement depletion with cobra venom factor alleviates acute hepatic injury induced by ischemia‑reperfusion

Mol Med Rep. 2018 Nov;18(5):4523-4529. doi: 10.3892/mmr.2018.9484. Epub 2018 Sep 14.


Increasing evidence has demonstrated that complement activation is required for ischemia‑reperfusion injury (IRI)‑induced hepatic damage, and cobra venom factor (CVF) can deplete the complement components. The aim of the current study was to investigate the effect and intrinsic mechanism of CVF pretreatment on IRI‑induced acute hepatic injury in rats. Acute hepatic injury in rats was induced by bone fracture to simulate trauma, followed by hemorrhage for 90 min, and then the rats were resuscitated for a period of 20 min of reperfusion. The survival times under different CVF treatment doses and schedules for rats with IRI were evaluated. Hepatic tissues and serum samples were analyzed for acute hepatic injury, complement activation, inflammatory mediator release and apoptosis at predetermined times and compared between the IRI group and the CVF pretreatment + IRI groups. Compared to the rats with IRI alone, the survival times were significantly improved among rats with IRI receiving a high‑dose or low‑dose CVF pretreatment (all P<0.01). Upon histological examination, severe hepatic damage was observed in the rats with IRI, accompanied by liver function deterioration, complement and membrane attack complex activation, inflammatory mediator release and hepatic cell apoptosis. CVF pretreatment significantly attenuated the hepatic injury through depletion of anaphylatoxic C5a and membrane attack complex C5b‑9 activation, and subsequent inhibition of inflammatory mediator release and hepatic cell apoptosis (all P<0.05). The results indicated that CVF pretreatment ameliorates IRI‑induced acute hepatic injury. However, further studies are required to determine whether this therapy could be a potential agent for the treatment of IRI injuries in clinical settings.

MeSH terms

  • Animals
  • Complement Activation / drug effects
  • Complement C5a / drug effects
  • Complement C5a / metabolism
  • Complement Membrane Attack Complex / drug effects
  • Complement Membrane Attack Complex / metabolism
  • Elapid Venoms / administration & dosage*
  • Elapid Venoms / chemistry
  • Fractures, Bone / complications
  • Fractures, Bone / physiopathology
  • Humans
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / physiopathology
  • Liver / drug effects
  • Liver / injuries
  • Liver / physiopathology
  • Liver Diseases / complications
  • Liver Diseases / drug therapy*
  • Rats
  • Reperfusion Injury / complications
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / physiopathology


  • Complement Membrane Attack Complex
  • Elapid Venoms
  • cobra venom factor
  • Complement C5a