Abstract: AIM: To investigate the effect of metallothionein(MT)on Doxorubicin (DOX)-induced superoxide generation.METHODS: Male wild type (MT+/+)and metallothionein-null (MT-/-)mice were divided into 4 groups respectively and were pretreated with either saline or ZnSO4(20 mg·kg^-1 , s.c.)at 24 h and 48 h before a single administration of DOX (15 mg·kg^-1 , i.p.)or equal volume of saline.Mice were sacrificed on the 4th day after treatment and their hearts were collected for analysis.RESULTS: Doxorubicin treatment significantly enhanced superoxide generation and depleted glutathione in MT+/+mice heart and these effects were even more severe in MT-/-mice.These toxic changes were greatly inhibited by zinc pretreatment in MT+/+ mice heart but not in MT--mice.Furthermore , zinc pretreatment significantly inhibited DOX-induced promotion of eNOS inMT+/+mice while similar effect did not occur in MT-/-mice.CONCLUSION: Metallothionein can inhibit DOX-induced enhancement of superoxide generation and protect the antioxidant defense system in mice heart , this effect is possibly associated with changes of eNOS expression.

Key words: metallothionein, Doxorubicin, zinc, superoxide, eNOS