Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways.

Abstract

In the present study, we have evaluated the chemopreventive potential of geraniol (GOH), an acyclic monoterpene alcohol against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in Wistar rats. Chronic treatment of Fe-NTA induced oxidative stress, inflammation and cellular proliferation in Wistar rats. The chemopreventive efficacy of GOH was studied in terms of xenobiotic metabolizing enzyme activities, LPO, redox status, serum toxicity markers and the expression of putative nephrotoxicity biomarker Kim-1, tumor suppressor gene P53, inflammation, cell proliferation and apoptosis related genes in the kidney tissue. Oral administration of GOH at doses of 100 and 200mg/kg b wt effectively suppressed renal oxidative stress and tumor incidence. Chemopreventive effects of GOH were associated with upregulation of xenobiotic metabolizing enzyme activities and down regulation of serum toxicity markers. GOH was able to down regulate expression of Kim-1, NFκB, PCNA, P53 along with induction of apoptosis. However, higher dose of GOH was more effective in modulating these multiple molecular targets both at transcriptional and protein level. These results provide a powerful evidence for the chemopreventive efficacy of GOH against renal carcinogenesis possibly by modulation of multiple molecular pathways.

• Authors: Shiekh Tanveer Ahmad, Wani Arjumand, Amlesh Seth, Sana Nafees, Summya Rashid, Nemat Ali, Sarwat Sultana
• Journal: Toxicology (Toxicology) Vol. 290 Issue 1 Pg. 69-81 (Nov 28 2011) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 21907755 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Acyclic Monoterpenes
• Antineoplastic Agents
• Ferric Compounds
• Terpenes
• Nitrilotriacetic Acid
• geraniol
• ferric nitrilotriacetate

Topics

• Acyclic Monoterpenes
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Drug Evaluation, Preclinical (methods)
• Ferric Compounds (toxicity)
• Kidney Neoplasms (chemically induced, metabolism, prevention & control)
• Male
• Nitrilotriacetic Acid (analogs & derivatives, toxicity)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects, physiology)
• Terpenes (pharmacology, therapeutic use)
• Treatment Outcome