Topiramate ameliorates abdominal aorta cross-clamping induced liver injury in rats

Saudi J Gastroenterol. 2014 Sep-Oct;20(5):297-303. doi: 10.4103/1319-3767.141690.

Abstract

Background and aim: Ischemia/reperfusion (I/R) injury in the liver occurs after a prolonged period of ischemia followed by restoration of hepatic blood perfusion. During the surgery of abdominal aorta, I/R injury causes damage to lower extremities and many organs, especially liver. The antioxidant and tumor necrosis factor-alpha (TNF-α) suppression effects of topiramate (TPM) have been reported in several studies. We evaluated the potential protective effect of TPM on cellular damage in liver tissue during I/R injury.

Materials and methods: Thirty male Wistar albino rats were divided into three groups: Control, I/R, and I/R plus TPM (I/R + TPM) groups. Laparotomy without I/R injury was performed in the control group. After laparotomy, cross-ligation of infrarenal abdominal aorta was applied for 2 h in I/R groups that was followed by 2 h of reperfusion. TPM (100 mg/kg/day) was orally administrated to the animals in the I/R + TPM group for seven consecutive days before I/R procedure.

Results: The I/R group's TNF-α and interleukin-6 (IL-6) levels were significantly higher than those of the control (P = 0.010; P = 0.002) and I/R + TPM groups (P = 0.010; P = 0.002, respectively). Asymmetric dimethyl arginine (ADMA) levels of I/R group were higher than the control (P = 0.015) and I/R + TPM groups. I/R caused serious histopathological damage to liver tissue; however, TPM led to very low histopathological changes.

Conclusion: Our data demonstrated that TPM treatment prominently decreases the severity of liver I/R injury. TPM pretreatment may have preventive effects on liver injury via I/R during intra-abdominal surgery.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Anticonvulsants / pharmacology*
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Enzyme-Linked Immunosorbent Assay
  • Fructose / analogs & derivatives*
  • Fructose / pharmacology
  • Interleukin-6 / blood
  • Ligation
  • Male
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Topiramate
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anticonvulsants
  • Biomarkers
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Topiramate
  • Fructose
  • N,N-dimethylarginine
  • Arginine
  • Aspartate Aminotransferases
  • Alanine Transaminase