Trimethoprim-sulfamethoxazole이 「톡소프라스마」감염 「마우스」의 혈액상에 미치는 영향」

Abstract

[한글]

「독소프라스마」 (Toxoplasma gondii)는 인수공통감염증(zoonoses)을 유발하는 원충성 기생충의 하나로 범세계적으로 분포되어 있으며 우리나라에서도 본 원충의 인체감염예와 선천성 「독소프라스마」증의 임상예가 보고된 바 있다. (Soh등, 1975 ; Choi등 1980 ; Chung등, 1980). 치료제로서는 purimethamine과 sulfadiazine의 병용 요법이 가장 널리 쓰이는 치료법으로 알려져 있으나 치료 도중 골수 기능의 저하등의 부작용이 많은 단점이 있다.

이에 본 연구는 부작용이 크지않고 우수한 항충효과를 가지는 Bactrim **(R) (trimethoprom + sulfamethoxazole)을 「독소프라스마」감염 「마우스」에 투여하고 숙주의 생명

연장에 미치는 효과와 혈액상에 미치는 영향을 관찰하고자 하였다.

항「독소프라스마」 약제로서 Bactrim을 감염 「마우스」에 투여하였을 결우 감염대조군에 비하여 유의하게 투약효과가 있음을 볼 수 있었다. 특히 그 용량을 「마우스」당 1일 trimethoprim 4mg, sulfamethoxazole 20mg으로 7일간 투약하였을 때에는 관찰 기간 1

개월까지 그 생존율이 83.3%이었고, trimethoprim 8mg, sulfamethoxazole 40mg으로 투약했을 대는 100%의 생존율을 보였다.

「독소프라스마」 감염「마우스」에 Bactrim을 투여하고 혈액상에 미치는 영향을 Daraprim**(R) (phrimethamine)과 Sulxin**(R) (sulfadimethoxine)병합투여군, 그리고 비투약감염군과 비교한 결과, 백혈구 수는 Bactrim 투여군과 Daraprim 및 Sulxin 병합투여군에

서 비투약감염 대조군에 비하여 오히려 증가하였으나 Daraprim 및 Sulxin 병합투여군에서의 백혈구수는 Bactrim 투여군에 비하여 현저히 감소되었다.

적혈구수와 혈소판수는 비투약감염군, Bactrim 투여군 그리고 Daraprim 및 Sulxin 병합투여군에서 일반적으로 정상 대조군에 비하여 감소되었으나 Daraprim 및 Sulxin 병합투여군의 적혈구수는 Bactrim 투여군에 비하여 더욱 감소되었다.

혈색소치는 두 약제 투여군과 「독소프라스마」 감염대조군에서 모두 정상대조군에 비하여 감소하였으나 약제 투여군 상호간에는 차이가 없었다.

Bactrim 투여군과 Daraprim 및 Sulxin 병합투여군에서 관찰 기간동안 일별 혈액상의 변동을 관찰한 실험결과를 요약하면 백혈구수는 Daraprim과 Sulxin 병합투여군에서 투약 후 3일, 4일, 18일에서 Bactrim 투여군에 비하여 감소하는 경향을 보이다가 투약 25일에서는 오히려 Bactrim 투여군에서 감소하는 경향을 보였다.

적혈구수는 투약 11일 후에는 Bactrim 투여군에서 감소하였으나 18일, 25일 후에는 Daraprim 과 Sulxin 병합투여군에서 더욱 감소하였다.

혈색소치는 투약 1일, 18일, 25일에서는 Daraprom과 Sulxin 병합 투여군에서 Bactrim 투여군에 비하여 감소하였으나 투약 4일, 11일째에서는 Bactrim 투여군에서 보다 감소하였다.

혈소판수는 투약 4일 후에 Daraprim과 Sulxin 병합투여군에서 Bactrim 투여군에 비하여 현저히 감소하였다.

이상의 결과로 보아 Bactrim**(R) (trimethoprim + sulfamethoxazole) 투여는 pyrimethamine과 sulfadimethoxine 병합투여시와 마찬가지로 우수한 항 「독소프라스마」효과를

보였으며, 숙주의 조혈기능에 대한 장애가 pyrimethamine 및 sulfadimethoxine 병합투여 경우에서보다 경미함을 알 수 있었다.

The Chemotherapeutic Efficacy of Trimethoprim-Sulfamethoxazole (Bactrim**(R)) in

Experimental Toxoplasmosis

Sung-Won Cho

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Prof. Keun-Tae Lee, M.D.

and Assoc. Prof. Pyung-Rim Chun, Ph. D,)

Toxoplasma gondii is a coccidian parasite of cosmopolitan distribution, causing

zoonotic toxiplasmosis. Relatively high seroepidemiological incidence of human

toxoplasmosis and congenital cases were also reported in Korea (Soh et al., 1975 ;

Choi et al ., 1980 ; Chung et al., 1980).

Among many anti-Toxoplasma drugs developed so far, pyrimethamine (Daraprim**(R))

is one of the favorable drugs in the clinics. However, side effects such as

leukopenia and thrombocytopenia by the treatment with pyrinethamine are practical

problems.

The present study aimed to evaluate the chemotherapeutic efficacy of

trimethoprim-sulfamethoxazole combination (Bactrim**(R)) in mouse model

experimentally infected with 1 ×10**5 trophozoites of T. gondii. The average

survival days and vitality of experimental mice were compared with control groups.

The best and minimal dosage of the drug was first determined in this experiment,

and hematological observations of mouse blood samples were done for the comparison

of side effects of Bactrim and Daraprim.

The results obtained in this stduy are summarized as follows:

1. Bactrim (trimethoprom + sulfamethoxazole) was a very potent anti-Toxoplasma

agent. The vitality of mice administered with 4.0mg of trimethoprim and 20mg of

sulfamethoxazole per mouse per day for 7 days was 83.3%, and 100% in mice

administered with two-fold concentrated doses.

2. The average numbers of white blood cells (W.B.C.) in the mouse groups treated

with Bactrim or Daraprim were increased rather than those only infected with

Toxoplasma. However, mice treated with Daraprim showed remarkably decreased numbers

of W.B.C. as compared with those treated with Bactrim.

3. Although the average numbers of red blood cells (R.B.C.) and platelets both in

the administered and only Toxoplasma-infected groups were all decreased as compared

with normal mice, the nubbers of R.B..C. in Daraprim-treated mice were more

decreased than in those treated with Bactrim.

4. The average levels of hemoglobin both in the administered and only

Toxoplasma-infected goups were decreased more than in normal mice. But, there was

no difference in the levels of hemoglobin between Bactrim-and Daraptim-treated

mouse groups.

In summarizing the results, it is elucidated that Bactrim was very effective and

applicable for the treatment of murine toxoplasmosis as well as Daraprim, and that

bone marrow depression of the hosts treated with Daraprim was more severe than

those treated with Bactrim.

[영문]

Toxoplasma gondii is a coccidian parasite of cosmopolitan distribution, causing zoonotic toxiplasmosis. Relatively high seroepidemiological incidence of human toxoplasmosis and congenital cases were also reported in Korea (Soh et al., 1975 ;

Choi et al ., 1980 ; Chung et al., 1980).

Among many anti-Toxoplasma drugs developed so far, pyrimethamine (Daraprim**(R)) is one of the favorable drugs in the clinics. However, side effects such as leukopenia and thrombocytopenia by the treatment with pyrinethamine are practical problems.

The present study aimed to evaluate the chemotherapeutic efficacy of trimethoprim-sulfamethoxazole combination (Bactrim**(R)) in mouse model experimentally infected with 1 ×10**5 trophozoites of T. gondii. The average survival days and vitality of experimental mice were compared with control groups.

The best and minimal dosage of the drug was first determined in this experiment, and hematological observations of mouse blood samples were done for the comparison of side effects of Bactrim and Daraprim.

The results obtained in this stduy are summarized as follows:

1. Bactrim (trimethoprom + sulfamethoxazole) was a very potent anti-Toxoplasma agent. The vitality of mice administered with 4.0mg of trimethoprim and 20mg of sulfamethoxazole per mouse per day for 7 days was 83.3%, and 100% in mice administered with two-fold concentrated doses.

2. The average numbers of white blood cells (W.B.C.) in the mouse groups treated with Bactrim or Daraprim were increased rather than those only infected with Toxoplasma. However, mice treated with Daraprim showed remarkably decreased numbers

of W.B.C. as compared with those treated with Bactrim.

3. Although the average numbers of red blood cells (R.B.C.) and platelets both in the administered and only Toxoplasma-infected groups were all decreased as compared with normal mice, the nubbers of R.B..C. in Daraprim-treated mice were more decreased than in those treated with Bactrim.

4. The average levels of hemoglobin both in the administered and only Toxoplasma-infected goups were decreased more than in normal mice. But, there was no difference in the levels of hemoglobin between Bactrim-and Daraptim-treated mouse groups.

In summarizing the results, it is elucidated that Bactrim was very effective and applicable for the treatment of murine toxoplasmosis as well as Daraprim, and that bone marrow depression of the hosts treated with Daraprim was more severe than those treated with Bactrim.