Kanamycin이 적혈구막에 미치는 영향

Abstract

[한글]

The Effect of Kanamycin on the Erythrocyte Membrane

Won Pyo Hong, M.D.

Department of Medical Science The Graduate School, Yonsei University

(Directed by Prof. Doo Hee Kang, M. D.)

Following discovery of kanamycin by Umezawa in 1957, this drug was found to be

effective on gram-positive bacteria, gram-negative bacteria and mycobacterial

infections.

However, it soon became apparent that this antibiotic like other drugs such as

streptomycin, dehydrostreptomycin and neomycin isolated from streptomyces could

Produce serious ototoxicity.

Numerous attempts were mode to investigate the nature of the toxic effect of

kanamycin on the inner ear, specially in the membranous cochlea. Hawkins (1957),

Benitez et al.(1962), Koide et al. (1966), Fartashidy et al. (1963), and Mendelsohn

and Katzenberg (1972) reported the pathological changes in the inner ear fellowing

administration of kanamycin. They found that outer hair cells were affected in a

greater extent than the inner hair cells of the organ of Corti.

The results of other investigators including Mizukoshi and Daly(1967), Ishii et

al (1968), Henderson et al. (1969), and Mendelsohn and Katzenberg (1972) showed a

reduced oxygen consumption rate and inhibition of certain enzyme activities such as

adenosine triphosphatase (ATPase), Iysosomal enzyme and succinic dehydrogenase in

the damaged membranous cochlea of guinea pigs treated with kanamycin. And they also

found that the ion Permeability across biological membrane and artificial membrane

was changed by certain antibiotics and kanamycin.

In this stuffy, the effect of kanamycin on osmotic hemolysis of erythrocyte,

mechanical resistance of erythrocyte to ultrasonification, Ca**++ binding on

erythrocyte membrane fragments and (22**Na permeability across erythrocyte membrane

was investigated. Also the effect of this agent on light scattering of hepatic

mitochondrial suspension was studied.

The results were summarise? as fellows;

1. Kanamycin inhibited osmotic hemolysis of erythrocyte in proportion to its

concentration and mitochondrial swelling was also inhibited by kanamycin. The

latter finding was similar to the result obtained in the presence of

2.4.-dinitrophenol (DNP).

2. An increase of permeability to 72Na across erythrocyte membrane by kanamycin

was found.

3. Mechanical resistance of erythrocyte membrane to ultrasonification was

increased following kanamycin administration.

4. A competitive inhibition of Ca**++ binding to erythrocyte membrane fragment

was found. However, unlike local anesthetics such as procaine, no effect on the

action potential of frog's sciatic nerve was demonstrated by application of

kanamycin to the nerve.

It is speculated by above findings, that kanamycin replaces Ca**++ from

biological membrane such as erythrocyte membrane, and also this agent stabilizes

the biological membrane without reducing permeability of ion ((22**Na) across the

membrane.

[영문]

Following discovery of kanamycin by Umezawa in 1957, this drug was found to be effective on gram-positive bacteria, gram-negative bacteria and mycobacterial infections.

However, it soon became apparent that this antibiotic like other drugs such as streptomycin, dehydrostreptomycin and neomycin isolated from streptomyces could Produce serious ototoxicity.

Numerous attempts were mode to investigate the nature of the toxic effect of kanamycin on the inner ear, specially in the membranous cochlea. Hawkins (1957), Benitez et al.(1962), Koide et al. (1966), Fartashidy et al. (1963), and Mendelsohn and Katzenberg (1972) reported the pathological changes in the inner ear fellowing administration of kanamycin. They found that outer hair cells were affected in a greater extent than the inner hair cells of the organ of Corti.

The results of other investigators including Mizukoshi and Daly(1967), Ishii et al (1968), Henderson et al. (1969), and Mendelsohn and Katzenberg (1972) showed a reduced oxygen consumption rate and inhibition of certain enzyme activities such as adenosine triphosphatase (ATPase), Iysosomal enzyme and succinic dehydrogenase in the damaged membranous cochlea of guinea pigs treated with kanamycin. And they also found that the ion Permeability across biological membrane and artificial membrane was changed by certain antibiotics and kanamycin.

In this stuffy, the effect of kanamycin on osmotic hemolysis of erythrocyte, mechanical resistance of erythrocyte to ultrasonification, Ca**++ binding on erythrocyte membrane fragments and (22**Na permeability across erythrocyte membrane

was investigated. Also the effect of this agent on light scattering of hepatic mitochondrial suspension was studied.

The results were summarise? as fellows;

1. Kanamycin inhibited osmotic hemolysis of erythrocyte in proportion to its concentration and mitochondrial swelling was also inhibited by kanamycin. The latter finding was similar to the result obtained in the presence of 2.4.-dinitrophenol (DNP).

2. An increase of permeability to 72Na across erythrocyte membrane by kanamycin was found.

3. Mechanical resistance of erythrocyte membrane to ultrasonification was increased following kanamycin administration.

4. A competitive inhibition of Ca**++ binding to erythrocyte membrane fragment was found. However, unlike local anesthetics such as procaine, no effect on the action potential of frog's sciatic nerve was demonstrated by application of kanamycin to the nerve.

It is speculated by above findings, that kanamycin replaces Ca**++ from biological membrane such as erythrocyte membrane, and also this agent stabilizes the biological membrane without reducing permeability of ion ((22**Na) across the membrane.