Chemopreventive evaluation of Tephrosia purpurea against N-nitrosodiethylamine-induced hepatocarcinogenesis in Wistar rats

J Pharm Pharmacol. 2012 Aug;64(8):1195-205. doi: 10.1111/j.2042-7158.2012.01503.x. Epub 2012 Mar 27.

Abstract

Objectives: The chemopreventive potential of Tephrosia purpurea extract (TPE) on N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma (HCC) in Wistar rats was assessed.

Methods: HCC was induced by a single intraperitoneal injection of NDEA (200 mg/kg) followed by subcutaneous injections of CCl(4) (3 ml/kg per week) for six weeks. After administration of the carcinogen, 200 and 400 mg/kg TPE were administered orally once a day throughout the study.

Key findings: The levels of liver cancer markers, including α-fetoprotein and carcinoembryonic antigen, were substantially increased by NDEA treatment. TPE treatment significantly reduced liver injury and restored the entire liver cancer markers. Additionally, TPE markedly normalized the activity of antioxidant enzymes, namely lipid peroxidation, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase in the liver of NDEA-treated rats. Treatment with TPE significantly reduced the nodule incidence and multiplicity in the carcinogen-bearing rats. Histological observations of the liver tissues correlated with the biochemical observations.

Conclusions: These findings powerfully support that T. purpurea prevented lipid peroxidation, suppressed the tumour burden, and promoted enzymatic and nonenzymatic antioxidant defence systems during NDEA-induced hepatocarcinogenesis. This might have been due to modulating the antioxidant defence status, which contributed to its anticarcinogenic potential.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Anticarcinogenic Agents / therapeutic use*
  • Carbon Tetrachloride
  • Carcinoembryonic Antigen / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Diethylnitrosamine
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Wistar
  • Tephrosia*
  • alpha-Fetoproteins / metabolism

Substances

  • Anticarcinogenic Agents
  • Carcinoembryonic Antigen
  • Plant Extracts
  • alpha-Fetoproteins
  • Diethylnitrosamine
  • Carbon Tetrachloride