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Antimicrobial Agents and Chemotherapy, June 2003, p. 1836-1841, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.1836-1841.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Tanshinone (Salviae miltiorrhizae Extract) Preparations Attenuate Aminoglycoside-Induced Free Radical Formation In Vitro and Ototoxicity In Vivo

Ai-Mei Wang,{dagger} Su-Hua Sha, Wojciech Lesniak, and Jochen Schacht*

Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0506

Received 22 November 2002/ Returned for modification 15 February 2003/ Accepted 18 March 2003

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.

* Corresponding author. Mailing address: Kresge Hearing Research Institute, University of Michigan, 1301 East Ann St., Ann Arbor, MI 48109-0506. Phone: (734) 763-3572. Fax: (734) 764-0014. E-mail: schacht{at}umich.edu.

{dagger} Present address: Department of Physiology, Jinzhou Medical College, 121001 Jinzhou, PR China.

Antimicrobial Agents and Chemotherapy, June 2003, p. 1836-1841, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.1836-1841.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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