Orientin mitigates 1, 2-dimethylhydrazine induced lipid peroxidation, antioxidant and biotransforming bacterial enzyme alterations in experimental rats

J Cancer Res Ther. 2018 Oct-Dec;14(6):1379-1388. doi: 10.4103/jcrt.JCRT_1363_16.

Abstract

Background: Colorectal cancer (CRC) is the second most diagnosed cancer often identified during the later stages of carcinogenesis. Orientin, a C-glycoside of luteolin, is well known for its versatile therapeutic action toward oxidative stress-induced cellular response may exert chemoprevention against CRC.

Materials and methods: In our study, we investigated the modulatory effect of orientin on lipid peroxidation, antioxidant defense, and biotransforming bacterial enzymes in 1, 2-dimethylhydrazine (DMH)-induced male albino Wistar rats in a dose-dependent manner. Animals were induced with DMH (20 mg/kg b.wt) for 15 weeks and administered with orientin in three different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg b. wt) daily under distinct phases (initiation, postinitiation, and the entire) for a total treatment period of 30 weeks.

Results: Orientin reinstates the alterations induced by DMH on lipid peroxidation and enzymatic antioxidants through its rich-free radical scavenging properties. In addition, orientin curtails the DMH-induced augmentation of biotransforming bacterial enzymes to inhibit the colon cancer progression. Overall, experimental findings suggest that orientin significantly inhibits the DMH induced colon cancer in all the three different doses, however, maximum inhibition was observed on supplementation of 10 mg/kg b.wt for the entire period of the study.

Conclusion: Hence, the intraperitoneal administration of 10 mg/kg b.wt orientin for the entire period is recommended for further molecular investigation to elucidate the precise mechanism of inhibition and so orientin can be used as a novel chemotherapeutic agent for CRC.

Keywords: 1; 2-dimethylhydrazine; antioxidants; bacterial enzymes; colorectal cancer; lipid peroxidation; orientin.

MeSH terms

  • 1,2-Dimethylhydrazine / adverse effects*
  • Animals
  • Antioxidants / metabolism*
  • Biotransformation / drug effects*
  • Carcinogenesis / chemically induced
  • Carcinogenesis / drug effects*
  • Carcinogenesis / metabolism
  • Colon / drug effects
  • Colon / metabolism
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Disease Models, Animal
  • Flavonoids / pharmacology*
  • Glucosides / pharmacology*
  • Lipid Peroxidation / drug effects*
  • Male
  • Oxidative Stress
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • Flavonoids
  • Glucosides
  • orientin
  • 1,2-Dimethylhydrazine