Efficacy of human beta-casein fragment (54-59) and its synthetic analogue compound 89/215 against Leishmania donovani in hamsters.
The characteristic feature of visceral leishmaniasis (VL) is the profound impairment of immune system of the infected host, which contributes significantly to the partial success of antileishmanial chemotherapy. Since in VL, cure is the combinatorial effect of drug and immune status of the host, the rationale approach towards antileishmanial chemotherapy would be to potentiate the immune functioning of the host to extract desired results. Towards this direction several rationally designed analogues of human beta-casein fragment (54-59) were evaluated for their ability to stimulate the non-specific resistance in hamsters against Leishmania donovani infection. By virtue of being derived from the food protein casein derivatives may be devoid of unwanted side effects associated with the substances of microbial origin, e.g. muramyl dipeptide (MDP). Out of this one peptide Val-Glu-Gly-Ile-Pro-Tyr (compound 89/215) had been reported to have such activity. In this communication, the prophylactic and therapeutic efficacy of the peptide along with its natural sequence has been evaluated in detail against experimental VL in hamsters. Their use as an adjunct to chemotherapy was also explored. Human beta-casein fragment, compound 89/215 and MDP were tested in vivo at various dose levels wherein compound 89/215 showed superiority over MDP at 3 mg/kg x 2 given intraperitoneally (i.p.). Compound 89/215 sensitized peritoneal macrophages acquired considerable resistance and only 24% of the cells were found infected in comparison to control peritoneal macrophages where 76.4% of the cells were found infected. Similarly, the efficacy of sodium antimony gluconate (SAG) in hamsters pretreated with compound 89/215 enhanced significantly (P < 0.001). This peptide also exhibited considerably good therapeutic efficacy when evaluated either alone or in combination with SAG in established infection of L. donovani.
Sharma
Preeti
P
Division of Parasitology, Central Drug Research Institute, Post Box No. 173, Lucknow 226001, India.
Singh
Nasib
N
Garg
Ravendra
R
Haq
Wahajul
W
Dube
Anuradha
A
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002364:Caseins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D006790:Host-Parasite Interactions; D006801:Humans; D007274:Injections, Intraperitoneal; D007893:Leishmania donovani / Q000187:drug effects* / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000628:therapy; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D008647:Mesocricetus / Q000469:parasitology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D000981:Antiprotozoal Agents; D002364:Caseins; D010446:Peptide Fragments; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000967:Antimony Sodium Gluconate