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Experimental Visceral Leishmaniasis: Role of trans-Aconitic Acid in Combined Chemotherapy

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Title Experimental Visceral Leishmaniasis: Role of trans-Aconitic
Acid in Combined Chemotherapy
 
Creator Kar, Sujata
Kar, Kalipada
Bhattacharya, Prabhat K
Ghosh, Dilip K
 
Subject Infectious Diseases and Immunology
 
Description We previously reported the effectiveness of trans-aconitic acid (TAA) as an antileishmanial compound. Inhibitory effects of TAA along with other antileishmanial compounds on transformation and in vitro multiplication in macrophage cultures of Leishmania donovani have been assessed. The efficacy of TAA in combined chemotherapy of experimental visceral leishmaniasis has also been evaluated along with those of commonly used antileishmanial compounds such as sodium stibogluconate, pentamidine, and allopurinol. TAA
(2 mM) inhibited transformation of L. donovani amastigotes to promastigotes by 95.2%, whereas in combination with pentamidine (5 ,ug/ml), allopurinol (10 ,ug/ml), and sodium stibogluconate (50 ,ug of Sb perml), it inhibited transformation by about 100, 99, and 98.5%, respectively. Sodium stibogluconate (20 ,ug of Sb per ml), pentamidine (2 ,ug/ml), and allopurinol (5 ,ug/ml) suppressed the amastigote burden in peritoneal macrophage cultures from BALB/c mice by 32.6, 56.1, and 46.3%, respectively. When these three drugs were used along with TAA (5 mM), the parasite loads were reduced by 100, 100, and 88.1%, respectively. TAA (5mM) alone suppressed the amastigote burden by 59.5%. In experimental visceral leishmaniasis in hamsters (1-month model), TAA at a dose of 200 mg/kg of body weight per day suppressed the spleen parasite load by
73.5%, and TAA in combination with sodium stibogluconate (50 mg of Sb per kg per day), pentamidine (8mg/kg/day), and allopurinol (15 mg/kg/day) inhibited the spleen parasite load by 98, 98.9, and 97%, respectively. Individually, these three drugs inhibited the parasite load by 35, 20, and 22%, respectively. TAA(400 mg/kg/day) inhibited the spleen parasite load by 99.8%, but an inhibitory effect of -100% was noted when TAA was supplemented with an antileishmanial drug. TAA was administered in experimental animals through oral, intraperitoneal, and intramuscular routes; the intramuscular route was most effective.
 
Publisher American Society for Microbiology
 
Date 1993
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2307/1/ANTIMICROBIAL_AGENTS_AND_CHEMOTHERAPY__V._37__(_11_)_2459%2D2465_;1993[9].pdf
Kar, Sujata and Kar, Kalipada and Bhattacharya, Prabhat K and Ghosh, Dilip K (1993) Experimental Visceral Leishmaniasis: Role of trans-Aconitic Acid in Combined Chemotherapy. Antimicrobial Agents and Chemotherapy, 37 (11). pp. 2459-2465.
 
Relation http://www.eprints.iicb.res.in/2307/