Nelumbo nucifera leaf extract treatment attenuated preneoplastic lesions and oxidative stress in the livers of diethylnitrosamine-treated rats

Environ Toxicol. 2017 Nov;32(11):2327-2340. doi: 10.1002/tox.22434. Epub 2017 Aug 14.

Abstract

Lotus (Nelumbo nucifera Gaertn) possesses antioxidant, hepatoprotective, and anticancer potential. This study determined the protective role of aqueous extract from Nelumbo nucifera leaves (NLE) against N-diethylnitrosamine (DEN)-induced oxidative stress and hepatocellular carcinogenesis in a sample of Sprague-Dawley rats. NLE was fed orally to rats in which hepatic carcinoma was induced with DEN for 12 weeks. Five groups of 12 rats each were used for the study: Group I (control group) rats received distilled water; Group II rats were induced with DEN; Group III rats were induced with DEN and cotreated with 0.5% NLE; Group IV rats were induced with DEN and cotreated with 1.0% NLE; and Group V rats were induced with DEN and cotreated with 2.0% NLE. Clinical chemistry, organ weight, inflammatory marker, protein expression, enzyme, and antioxidant analyses were conducted. NLE administration to rats resulted in significantly decreased levels of serum alanine aminotransferase, aspartate aminotransferase, and albumin, which is indicative of hepatocellular damage, compared with the control group. DEN-induced oxidative stress was inhibited by NLE and this inhibition was paralleled by decreased lipid peroxides and increased glutathione transferase, superoxide dismutase, catalase, and glutathione peroxidase activity in liver tissues. The status of nonenzymatic antioxidants, such as reduced glutathione, was also found to be increased in NLE-administered rats. Furthermore, NLE decreased tumor size, hepatic Rac1, PKCα, and GSTπ expressions compared with the DEN-only group. Thus, supplementation of NLE reduced the adverse changes that occur because of liver cancer. These results prove that NLE protects against liver carcinogenesis induced because of treatment with DEN through blocking lipid peroxidation, hepatic cell damage, and enhancing the antioxidant defense system.

Keywords: Nelumbo nucifera leaves; Rac1; diethylnitrosamine; hepatocellular carcinoma; oxidative stress.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antioxidants / metabolism
  • Aspartate Aminotransferases / metabolism
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Catalase / metabolism
  • Diethylnitrosamine*
  • Glutathione / metabolism
  • Glutathione Transferase / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Nelumbo / chemistry*
  • Oxidative Stress / drug effects*
  • Plant Extracts / therapeutic use*
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / drug therapy*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Plant Extracts
  • Diethylnitrosamine
  • Catalase
  • Superoxide Dismutase
  • Glutathione Transferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione