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


CONCLUSIONS
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.
Kaji
H
H
Department of Clinical Pharmacy, School of Pharmacy, Shujitsu University, Nishigawara, Okayama, Japan.
Inukai
Y
Y
Maiguma
T
T
Ono
H
H
Teshima
D
D
Hiramoto
K
K
Makino
K
K
D000493:Allopurinol / Q000737:chemistry / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D052160:Benzothiazoles / Q000737:chemistry; D044182:Benzylisoquinolines / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry; D052016:Mucositis / Q000139:chemically induced* / Q000517:prevention & control*; D016877:Oxidants / Q000737:chemistry; D010851:Picrates / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D044182:Benzylisoquinolines; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D016877:Oxidants; D010851:Picrates; D017382:Reactive Oxygen Species; D013451:Sulfonic Acids; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D017665:Hydroxyl Radical; D000493:Allopurinol; C004931:1,1-diphenyl-2-picrylhydrazyl