Kanamycin과 kanendomycin이 백서 간의 mitochondria의 oxidative phosphorylation에 미치는 영향

Abstract

[한글]

[영문]

A comparative study was carried out on the effect of kanamycin and kanendomycin on oxidative phosphorylation of mitochondria in the isolated rat liver.

Hawkins (1959), Benitez et al. (1962) and Stupp et al. (1966) reported the pathological changes induced in the cochlea following the administration of ototoxic antibiotics. In the cochlea they found an irregular cellular pattern with swelling or disappearance of tee nucleus fellowing an overdose of the ototoxic antibiotics was administered Stupp et al. (1966) speculated that these pathological changes might be due to the delayed excretion of the antibiotics accumulated in the endolymph.

Other authors, Chance and Williams (1955), Packer (1957), Wadkins (1961, 1962), Bard (1961), El-Mofty and EI-Serafy (1966), Pinna (1967), Freeman (1967, 1968) and Firkin (1969), also reported a disturbance in oxygen consumption, a change in cellular membrane permeability and inhibition of protein synthesis.

As this moment, whether or not the reduced oxygen consumption in cochlear'.tissue and the disturbance of oxidative phosphorylation in mitochondria are closely related to the underlying mechanism of ototoxicity induced by these antibiotics is not clear. However, it is speculated that these antibiotics generally act on the biological membrane, thus inducing a change in cellular permeability and a disturbance in oxidative phosphorylation of the cochlear mitochondria.

If this assumption is correct, the magnitude of the inhibiting of oxidative phosphorylation could be Studied in liver mitochondria instead of cochlear mitochondria.

In 1968, kancndomycin was developed by Umezawa in an attempt to develop an antibiotic with lesser ototoxicity. So far no experimental study hart bun carried out to compare its toxicity with that of kanamycin.

In the present, a comparative study of the effect of kanamycin and kanendomycin on oxidative phosphorylation was done.

Using trio method of Hogeboom (1955) the liver mitochondria from rat were isolated Oxygen consumption was measured polarographically using a stationary platinum elutrode. The amount of ATP synthetized from ADP during the phosphorylation process was measured using talc dessicated tail of the fire fly

(Weichselbaum, 1946). The rate of oxygen consumption, P/O ratio and acceptor control ratio were calculated.

The results were summarized as fellows.

1. Kanamycin and kanendomycin reduce the rate of oxygen consumption and acceptor control ratio in liver mitochondria of rats. However, the dose-response curve shows that kanamycin is more potent than kanendemycin in reducing both the rate of oxygen

consumption and the accepter control ratio if equivalent doses are compared

2. The amount of ATP synthetized from ADP during oxidative phosphorylation is reduced by both antibiotics. However, the potency of kanamycin was stronger than that of kancndomycin in reducing ATP synthesis in the range of doses employed front

286 ㎍/ml to 4320㎍/ml.

3. The degree of reduction in ATP synthesis and reduction in oxygen consumption by both antibiotics is Proportional to the dose added, i.e. the higher the dose, the lower the amount of oxygen consumed and ATP synthetized.

4. The degree of reduction in oxidative phosphorylation induced by the addition of kanamycin. depends upon the duration of the time during which kanamycin acts on the mitochondria, i.e. the longer the incubation of mitochondria with kanamycin, the greater the inhibition of the oxidative phosphorylation.

5. From the above findings, it is concluded that kanendomycin demonstrates a lesser ototoxicity than kanamycin. The ototoxicity induced by kanamycin may be increased because of the delay in its excretion from endolymph.