TRANSGENIC MICE WITH ELEVATED LEVEL OF CUZNSOD ARE HIGHLY SUSCEPTIBLETO MALARIA INFECTION

Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O-2(.-) into H2O2, Constitutive overexpression of CuZnSOD in cells an d animals creates an indigenous oxidative stress that predisposes them to added insults. In this study, we used transgenic CuZnSOD (Tg-CuZnS OD) mice with elevated levels of CuZnSOD to determine whether overexpr ession of CuZnSOD affected the susceptibility of these mice to plasmod ium infection. Acute malaria is associated with oxidative stress, medi ated by redox-active iron released from the infected RBC. Two independ ently derived Tg-CuZnSOD lines showed higher sensitivity than control mice to infection by Plasmodium berghei (P. berghei), reflected by an earlier onset and increased rate of mortality. Nevertheless, while Tg- CuZnSOD mice were more vulnerable than control mice, the levels of par asitemia were comparable in both strains. Moreover, treatment of infec ted red blood cells (RBC) with oxidative stress inducers, such as asco rbate or paraquat, reduced the viability of parasites equally in both transgenic and control RBC, This further confirms that increased CuZnS OD does not support plasmodia development. The data are consistent wit h the possibility that the combination of increased redox-active iron and elevated H2O2 in the plasmodium-infected Tg-CuZnSOD mice, led to a n enhanced Fenton's reaction-mediated HO. production, and the resultin g oxidative injury renders the transgenic mice more vulnerable to para site infection. (C) 1998 Elsevier Science Inc.