Tanshinone (Salviae miltiorrhizae extract) preparations attenuate aminoglycoside-induced free radical formation in vitro and ototoxicity in vivo.
Antioxidant therapy protects against aminoglycoside-induced ototoxicity in animal models. A clinically suitable antioxidant must not affect the therapeutic efficacy of aminoglycosides or exhibit any side effects of its own. In addition, the treatment should be inexpensive and convenient in order to be implemented in developing countries where the use of aminoglycosides is most common. Standardized Salviae miltiorrhizae extracts (Danshen) are used clinically in China and contain diterpene quinones and phenolic acids with antioxidant properties. We combined in vitro and in vivo approaches to investigate the effect of a clinically approved injectable Danshen solution on aminoglycoside-induced free radical generation and ototoxicity. In vitro, Danshen inhibited gentamicin-dependent lipid peroxidation (formation of conjugated dienes from arachidonic acid), as well as the gentamicin-catalyzed formation of superoxide (in a lucigenin-based chemiluminescence assay) and hydroxyl radicals (oxidation of N,N-dimethyl-p-nitrosoaniline). Danshen extracts were then administered to adult CBA mice receiving concurrent treatment with kanamycin (700 mg/kg of body weight twice daily for 15 days). Auditory threshold shifts induced by kanamycin (approximately 50 dB) were significantly attenuated. Danshen did not reduce the levels in serum or antibacterial efficacy of kanamycin. These results suggest that herbal medications may be a significantly underexplored source of antidotes for aminoglycoside ototoxicity. Such traditional medicines are widely used in many developing countries and could become an easily accepted and inexpensive protective therapy.
Wang
Ai-Mei
AM
Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0506, USA.
Sha
Su-Hua
SH
Lesniak
Wojciech
W
Schacht
Jochen
J
D045784:Abietanes; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000097:blood; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005839:Gentamicins / Q000009:adverse effects*; D034381:Hearing Loss / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D017665:Hydroxyl Radical / Q000378:metabolism; D007612:Kanamycin / Q000009:adverse effects* / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D016877:Oxidants / Q000009:adverse effects / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D045784:Abietanes; D000900:Anti-Bacterial Agents; D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; D005839:Gentamicins; D016877:Oxidants; D010616:Phenanthrenes; C021751:tanshinone; D013481:Superoxides; D017665:Hydroxyl Radical; D007612:Kanamycin