Combination of ascorbate and alpha-tocopherol as a preventive therapy against structural and functional defects of erythrocytes in visceral leishmaniasis.
The redox unbalance in erythrocytes has been found to contribute significantly in the development of anemia in visceral leishmaniasis (VL). The present study revealed enhanced production of reactive oxygen species (ROS) and gradual depletion of alpha-tocopherol and ascorbate in the erythrocytes of infected animals. The response of erythrocytes to chronic treatment with antioxidants was studied in hamsters during leishmanial infection. Treatment with a combination of alpha-tocopherol and ascorbate proved to be the most effective preventive for the proteolytic degradation of erythrocyte membrane. Erythrocytes from infected animals were thermally more sensitive compared to the control ones. Combination of both antioxidants was most successful in resisting heat induced structural defects in the cells. Cross-linking of membrane proteins subsequent to oxidative damage in the red cells was accompanied by the formation of high molecular weight protein band at the top of the resolving gel in the presence of the cross-linking agent dimethyladepimidate (DMA). Marked inhibition of cross-linking was observed with combination of both antioxidants. Treatment with alpha-tocopherol and ascorbate together could withstand osmotic lysis of erythrocytes in the infected animals very efficiently. Decreased hemoglobin (Hb) level was successfully replenished and was coupled with significant increase in the life span of red cells after treating the animals with both antioxidants. Results indicate better efficacy of the combination therapy with alpha-tocopherol and ascorbate in protecting the erythrocytes from structural and functional damages during leishmanial infection.
Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, India.
Gargi
G
Sen
Rupa
R
Mukhopadhaya
Jharna
J
Ghosal
Tuli
T
Biswas
D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000378:metabolism / Q000627:therapeutic use*; D006224:Cricetinae; D003432:Cross-Linking Reagents; D004338:Drug Combinations; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology; D006454:Hemoglobins / Q000378:metabolism; D007893:Leishmania donovani / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008647:Mesocricetus; D009996:Osmotic Fragility / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000378:metabolism / Q000627:therapeutic use*
D000975:Antioxidants; D003432:Cross-Linking Reagents; D004338:Drug Combinations; D006454:Hemoglobins; D017382:Reactive Oxygen Species; D024502:alpha-Tocopherol; D001205:Ascorbic Acid