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Citral inhibits N-nitrosodiethylamine-induced hepatocellular carcinoma via modulation of antioxidants and xenobiotic-metabolizing enzymes.

Abstract
Hepatocellular carcinoma (HCC) ranks the sixth position among various cancers worldwide. Recent research shows that natural and dietary compounds possess many therapeutic effects. Citral is a monoterpene aldehyde that contains geranial and neral. The present study was considered to study the role of citral against N-nitrosodiethylamine (NDEA)-induced HCC via modulation of antioxidants and xenobiotic-metabolizing enzymes in vivo. NDEA-alone-administered group II animals profoundly showed increased tumor incidence, reactive oxygen species, liver marker enzyme levels, serum bilirubin levels, tumor markers of carcinoembryonic antigen, α-fetoprotein, proliferative markers of argyrophilic nucleolar organizing regions, proliferating cell nuclear antigen (PCNA) expressions, phase I xenobiotic-metabolic enzymes and simultaneously decreased antioxidants, and phase II enzymes levels. Citral (100 mg/kg b.w.) treatment significantly reverted the levels in group III cancer-bearing animals when compared to group II cancer-bearing animals. In group IV animals, citral-alone administration did not produce any adverse effect during the experimental condition. Based on the results, citral significantly inhibits the hepatocellular carcinogenesis through restoring the antioxidants and phase II xenobiotic-enzyme levels; thereby, it strongly proves as an antiproliferative agent against rat HCC.
AuthorsPalanisamy Krishnan, Jagan Sundaram, Sharmila Salam, Nirmala Subramaniam, Ashok Mari, Gopalakrishnan Balaraman, Devaki Thiruvengadam
JournalEnvironmental toxicology (Environ Toxicol) Vol. 35 Issue 9 Pg. 971-981 (Sep 2020) ISSN: 1522-7278 [Electronic] United States
PMID32302048 (Publication Type: Journal Article)
Copyright© 2020 Wiley Periodicals, Inc.
Chemical References
  • Acyclic Monoterpenes
  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Carcinoembryonic Antigen
  • Proliferating Cell Nuclear Antigen
  • alpha-Fetoproteins
  • Diethylnitrosamine
  • citral
Topics
  • Acyclic Monoterpenes (therapeutic use)
  • Animals
  • Antineoplastic Agents, Phytogenic (therapeutic use)
  • Antioxidants (metabolism)
  • Carcinoembryonic Antigen (analysis)
  • Carcinoma, Hepatocellular (drug therapy, enzymology, pathology)
  • Cell Line, Tumor
  • Diethylnitrosamine
  • Humans
  • Liver Function Tests
  • Liver Neoplasms, Experimental (drug therapy, enzymology, pathology)
  • Male
  • Proliferating Cell Nuclear Antigen (metabolism)
  • Rats
  • Rats, Wistar
  • alpha-Fetoproteins (analysis)

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