- Email: [email protected]
In vitro antileishmanial properties of pentavalent antimonial compounds
284 TRANSACTIONS
OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, VOL. 76, No. 2, 1982.
References
Fakunle, Y. M. & Whittle, H. C. (1981). Hepatitis-B virus infection in patients with leprosy: a serological study in a leprosarium in Northern Nigeria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 75, 623-625.
Accepted for publication 12th January,
rophages increased according to reducing drug concentration. The EDSOs determined in three reoresentative experiments are shown in the table. ‘ Table I-The calculated ED50 (p95 limits) pg Sb/ml of sodium stibogluconate and meghunine antimoniate against mouse peritoneal macrophages infected with amastigotes of Leishmania donovani in vitro
1982. Experiment
In vitro antileishmanial properties of pentavalent antimonial compounds
The drugs of choice for treatment of leishmaniasis are the pentavalent antimonial compounds, sodium stibogluconate and meglumine antimoniate. The mode of action of these compounds has been the subject of much discussion since the compounds have little or no activity against the promastigote form in culture (see NARAIN & DUTTA, 1978; JIMINEZ & ERCOLI, 1965) whereas the experimental in viva infection does respond to treatment with antimonial compounds (BEVERIDGE,1963). Berman and his colleagueshave recently shown that the antimonials have a direct antiparasite effect against the amastigotesof Leishmania donovani and L. tropica (L. t. major) in experimentally infected human monocyte-derived macrophages in vitro (BERMAN& WYLER.
1980).
The purpose of this letter is to record results of studies similar to Berman, which were set UD indeoenA dently of those of the American workers. In our experiments, mouse peritoneal macrophages were harvested from mice (Charles Rivers strain CDl) and infected with L. donovani stocks (HV3, LV9) amastigotes prepared from the spleen of infected hamsters. The infected macrophages were then exposed for seven days to medium (RPM1 1640 + 10% foetal calf serum) containing various concentrations of sodium stibogluconate or meglumine antimoniate. At the end of the exposure period, the macrophageswere !ixed, stained with Giemsa stam and the proportion of macrophages free from amastigotes were counted microscopically. Four replicates were set up with each drug concentration and 100 macrophages counted from each replicate. The results showed that both antimonial compounds reduced the proportion of infected macrophagesand at 81 pg/ml of both sodium stibogluconate and meglumine antimoniate all macrophageswere microscopically free from amastigotes. At lower concentrations, the proportion of infected mac-
CORRESPONDENCE
Sodium stibogluconate
Meglumine antimoniate*
2.34 (3.04-1.73) 1 8.12 (9.54- 6.86) 1.39 (2.29-0.46) 2 13.05 (14.26-11.84) 2.68 (4.94-0.86) 3 11.40 (12.52-10.38) *Antimony content from the theoretical figure.
These results confirm the previous work by Berman and his colleagues that the antimonial compounds showed a direct effect against the amastigotes. The mouse peritoneal macrophagesystem is also shown to be of value for the studv of the antileishmanial properties of existing drugs and novel compounds. These experiments will be described in greater detail in a future publication. R. A. NEAL P. J. MATTHEWS Department of Parasitology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS, UK References
Berman, J. D. 8z Wyler, D. J. (1980). An in vitro model for investigation of chemotherapeutic agents in leishmaniasis. Journal of Infectious Diseases, 142, 83-86.
Beveridge, E. (1963). Chemotherapy of leishmaniasis. In: Experimental Chemotherapy Vol 1. Schnitzer, R. J. & Hawking, F. (Editors). London: Academic Press., VD. *t 257-287. Jiminez, G. de & Ercoh, N. (1965). Effect of drugs on various Leishmania isolates and succinic dehydrogenaseinhibition. Experimental Parasitology, 17, 302-308.
Narain, L. & Dutta, G. P. (1978). Cultivation and in vitro chemotherapeutic studies on Leishmania donovani. Indian Journal of Parasitology, 2, 83-86.
Accepted for publication 26th January,
1982.
OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, VOL. 76, No. 2, 1982.
References
Fakunle, Y. M. & Whittle, H. C. (1981). Hepatitis-B virus infection in patients with leprosy: a serological study in a leprosarium in Northern Nigeria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 75, 623-625.
Accepted for publication 12th January,
rophages increased according to reducing drug concentration. The EDSOs determined in three reoresentative experiments are shown in the table. ‘ Table I-The calculated ED50 (p95 limits) pg Sb/ml of sodium stibogluconate and meghunine antimoniate against mouse peritoneal macrophages infected with amastigotes of Leishmania donovani in vitro
1982. Experiment
In vitro antileishmanial properties of pentavalent antimonial compounds
The drugs of choice for treatment of leishmaniasis are the pentavalent antimonial compounds, sodium stibogluconate and meglumine antimoniate. The mode of action of these compounds has been the subject of much discussion since the compounds have little or no activity against the promastigote form in culture (see NARAIN & DUTTA, 1978; JIMINEZ & ERCOLI, 1965) whereas the experimental in viva infection does respond to treatment with antimonial compounds (BEVERIDGE,1963). Berman and his colleagueshave recently shown that the antimonials have a direct antiparasite effect against the amastigotesof Leishmania donovani and L. tropica (L. t. major) in experimentally infected human monocyte-derived macrophages in vitro (BERMAN& WYLER.
1980).
The purpose of this letter is to record results of studies similar to Berman, which were set UD indeoenA dently of those of the American workers. In our experiments, mouse peritoneal macrophages were harvested from mice (Charles Rivers strain CDl) and infected with L. donovani stocks (HV3, LV9) amastigotes prepared from the spleen of infected hamsters. The infected macrophages were then exposed for seven days to medium (RPM1 1640 + 10% foetal calf serum) containing various concentrations of sodium stibogluconate or meglumine antimoniate. At the end of the exposure period, the macrophageswere !ixed, stained with Giemsa stam and the proportion of macrophages free from amastigotes were counted microscopically. Four replicates were set up with each drug concentration and 100 macrophages counted from each replicate. The results showed that both antimonial compounds reduced the proportion of infected macrophagesand at 81 pg/ml of both sodium stibogluconate and meglumine antimoniate all macrophageswere microscopically free from amastigotes. At lower concentrations, the proportion of infected mac-
CORRESPONDENCE
Sodium stibogluconate
Meglumine antimoniate*
2.34 (3.04-1.73) 1 8.12 (9.54- 6.86) 1.39 (2.29-0.46) 2 13.05 (14.26-11.84) 2.68 (4.94-0.86) 3 11.40 (12.52-10.38) *Antimony content from the theoretical figure.
These results confirm the previous work by Berman and his colleagues that the antimonial compounds showed a direct effect against the amastigotes. The mouse peritoneal macrophagesystem is also shown to be of value for the studv of the antileishmanial properties of existing drugs and novel compounds. These experiments will be described in greater detail in a future publication. R. A. NEAL P. J. MATTHEWS Department of Parasitology, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS, UK References
Berman, J. D. 8z Wyler, D. J. (1980). An in vitro model for investigation of chemotherapeutic agents in leishmaniasis. Journal of Infectious Diseases, 142, 83-86.
Beveridge, E. (1963). Chemotherapy of leishmaniasis. In: Experimental Chemotherapy Vol 1. Schnitzer, R. J. & Hawking, F. (Editors). London: Academic Press., VD. *t 257-287. Jiminez, G. de & Ercoh, N. (1965). Effect of drugs on various Leishmania isolates and succinic dehydrogenaseinhibition. Experimental Parasitology, 17, 302-308.
Narain, L. & Dutta, G. P. (1978). Cultivation and in vitro chemotherapeutic studies on Leishmania donovani. Indian Journal of Parasitology, 2, 83-86.
Accepted for publication 26th January,
1982.