Date of Defense

Spring 4-10-1996


Biological Sciences

First Advisor

Sylvia Culp, Philosophy

Second Advisor

Hartmut Jaeschke, Upjohn Company


The protective effect of tirilazad mesylate (U74006F) in vivo was investigated in isolated, perfused rat livers exposed to lipid peroxidation, hypoxia, and ischemia/reperfusion. Animals were treated with either U74006F dissolved in citrate buffer (3 mg/kg, 1.5 mg/mL buffer) or citrate buffer alone at 120 and 60 minutes before surgery. U74006F treatment of liver exposed to lipid peroxidation by 500 mM t-butyl hydroperoxide perfusate did not attenuate MDA, LDH, or glutathione efflux when compared to the control. U74006F did not protect against, but aggravated hypoxic injury as characterized by LDH efflux and file flow. However, treatment with U74006F significantly attenuated initial phase of injury in livers exposed to ischemia and short term reperfusion. We concluded that U74006F does not prevent injury in vivo by lipid peroxidation inhibition, as generally acknowledged, but possibly be a membrane stabilization mechanism.

Access Setting

Honors Thesis-Campus Only