PHYSICOCHEMICAL PROPERTIES OF STREPTOMYCIN IN RELATIONSHIP TO ITS VESTIBULOTOXICITY

G. Meza1, N. Barba-Behrens2, G Guerra1, O. Granados1, C. Hernandez3 , A. Toxqui2

 

 

1 Instituto De Fisiologia Celular,

 

2 Facultad De Quimica, Unam.,

 

3 Escuela De Ciencias Biologicas, Ipn,

Mexico, D.F., Mexico

 

Ever since streptomycin (STP) was developed and used in the clinics against Mycobacterium tuberculosis, its toxic effects for the vestibular function was described, its cellular target being the sensory (hair) cells. Chemically, STP is composed of three molecular entities: streptidine (STD, a derivative of inositol, and two sugars: streptose (Stose) and nmethylglucosamine (n-m-GLUN) joined to one another, through respective glycosidic bends. Other related aminoglycosides such as gentamycin (GEN) or kanamycin (KAN) were developed to substitute STP; although GEN is less toxic for the vestibule it is cochleotoxic and, KAN is exclusively cochleotoxic. In their chemical structure, they differ in the group substituents of STD and Stose, the n-m-GLUN ring remains intact and it is related probably to the antimicrobial activity.

Our group thesis is that STP might be vestibulotoxic due to interaction of its STD ring, probably through the positively charged guanidine groups, to vestibular structures involved in the transduction process, such as the hair cell membranes. To demonstrate this proposal, we performed a series of in vitro experiments in which STD was obtained from STP by prolonged acid hydrolysis; this procedure rendered pure STD by elemental analysis, X-ray crystalography and spectrophotometric measurements. Its capability to displace bound 3H-spermidine (a structural analogue of STD) from isolated membranes of vestibular organs was attained, and compared with displacement capacities of STP itself; guanidine (GUA), and n-aGLUN. The displacement properties of cold spermidine, STP, STD, GUA and n-aGLN for 3H-spermidine resulted in the following percentage order: 96, 88, 66, 48 and 15, respectively. These results suggest that as predicted, STP interacts with vestibular membranes probably through the guanidine group(s) of the STD moeity. Other experiments which include GEN and KAN are presently being carried out. Financed partially by GRANT 4712-N9407 from CONACyT (Mexico) to G.M.