Radical scavenging activity of bisbenzylisoquinoline alkaloids and traditional prophylactics against chemotherapy-induced oral mucositis.

Abstract

BACKGROUND AND OBJECTIVE:

Oral mucositis is a major severe toxic side-effect of systemic chemotherapy and irradiation in patients with cancer. Various free radical scavengers have been shown to prevent chemotherapy-induced skin necrosis. The objective of this study was to determine the antioxidant activity of a bisbenzylisoquinoline alkaloidal compound (BIQAC) and a series of chemicals, including allopurinol, used clinically for the treatment of chemotherapy-induced mucositis.

METHODS:

Allopurinol, melatonin, camostat mesilate, gabexate mesilate, hydroquinone and BIQAC were tested for their radical scavenging activities on four different radical species: 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) cation radical (ABTS(*+)) using standard methods, and superoxide anion radical (O(2) (-)) and hydroxyl radical (OH(*)) using electron spin resonance.

RESULTS:

Allopurinol had radical scavenging activity against O(2) (-) only. Melatonin had strong radical scavenging activity against ABTS(*+), and weak activity against DPPH radical and OH(*). Camostat mesilate had weak radical scavenging activity against OH(*). Gabexate mesilate had no radical scavenging activity against any of these radicals. Hydroquinone had strong radical scavenging activity against DPPH radical and ABTS(*+), and moderate activity against both O(2) (-) and OH(*). BIQAC had moderate radical scavenging activity against DPPH radical, strong radical scavenging activity against ABTS(*+) and O(2) (-), and weak activity against OH(*).

CONCLUSION:

The BIQAC had the most braod-spectrum radical scavenging activity, suggesting that it may be effective against chemotherapy-induced mucositis. These findings also suggest that this radical-scavenging activity screening method, against four kinds of radicals, may be useful for the screening of radical scavenging activity of new natural and synthetic chemicals.

• Authors: H Kaji, Y Inukai, T Maiguma, H Ono, D Teshima, K Hiramoto, K Makino
• Journal: Journal of clinical pharmacy and therapeutics (J Clin Pharm Ther) Vol. 34 Issue 2 Pg. 197-205 (Apr 2009) ISSN: 1365-2710 [Electronic] England
• PMID: 19250140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Antineoplastic Agents
• Benzothiazoles
• Benzylisoquinolines
• Biphenyl Compounds
• Free Radical Scavengers
• Oxidants
• Picrates
• Reactive Oxygen Species
• Sulfonic Acids
• 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
• Hydroxyl Radical
• Allopurinol
• 1,1-diphenyl-2-picrylhydrazyl

Topics

• Allopurinol (chemistry, pharmacology)
• Antimetabolites, Antineoplastic (chemistry, pharmacology)
• Antineoplastic Agents (adverse effects)
• Benzothiazoles (chemistry)
• Benzylisoquinolines (chemistry)
• Biphenyl Compounds (chemistry)
• Dose-Response Relationship, Drug
• Electron Spin Resonance Spectroscopy
• Free Radical Scavengers (chemistry)
• Hydroxyl Radical (chemistry)
• Mucositis (chemically induced, prevention & control)
• Oxidants (chemistry)
• Picrates (chemistry)
• Reactive Oxygen Species (chemistry)
• Structure-Activity Relationship
• Sulfonic Acids (chemistry)