Effect of nifedipine on oxidative damage of erythrocytes in Plasmodium berghei-infected mice.
It is known that the calcium channel blocker (CCB), nifedipine, can inhibit phagocyte oxidative burst in Plasmodium berghei-infected mice. The extent of immunopathological changes as seen by the course of infection and membrane lipid peroxidation in nifedipine-treated mice was examined in comparison with untreated mice at different parasite loads. The glutathione antioxidant system was also studied in these animals to assess its capacity to neutralize reactive oxygen species (ROS) in infected erythrocytes. The survival period of nifedipine-treated, infected mice decreased significantly. It was observed that the accumulation of reduced glutathione was greater and the decrease in glutathione peroxidase activity was less marked in drug-treated animals, suggesting better protection of the parasites against oxidative injury. The accumulation of the lipid peroxidation product, malonyldialdehyde was significantly lower in nifedipine-treated animals at all parasitemia levels studied, indicating decreased ROS generation and parasite damage. These observations reveal the shortcomings of using CCB to reverse the chloroquine resistance in malaria as this would minimize oxidative damage of parasitized red cells and phagocyte-mediated parasite killing.
Mohan
K
K
Department of Parasitology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Dubey
M L
ML
Ganguly
N K
NK
Kalra
A
A
Mahajan
R C
RC
D000818:Animals; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008288:Malaria / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology* / Q000627:therapeutic use; D010962:Plasmodium berghei; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D005978:Glutathione; D009543:Nifedipine