Protection against post-ischemic mitochondrial injury in rat liver by silymarin or TUDC

Background: Hepatic ischemia/reperfusion (I/R) injury is characterized by features such as cholestasis. Mitochondria become susceptible to damage during ischemia and after reperfusion. The aim of this study was to determine if silymarin and tauroursodcoxycholic acid (TUDC), would prevent impairment of liver mitochondrial function following I/R injury. Methods: Livers of male Wistar rats were subjected to 45 min of hepatic ischemia. During the 90 min of reperfusion, livers were perfused with either vehicle, silymarin, or TUDC. Changes in membrane potential, mitochondrial respiration as well as susceptibility to mitochondrial permeability transition (MPT) induction were evaluated and endogenous adenine nucleotides were measured. Results: In rats subjected to I/R, compared with the control group, a severe impairment of mitochondrial bioenergetics was observed. State 3 respiration was decreased and state 4 enhanced, associated with lower membrane potential developed following succinate energization. An increased susceptibility to MPT induction by calcium/phosphate was also observed. The effects of I/R injury were ameliorated in the presence of silymarin but not TUDC. Similarly, ATP levels following I/R were lower, in comparison with the control group and the silymarin treatment but not TUDC. Conclusion: Thus, silymarin, but not TUDC, prevents the most significant changes that occur in mitochondria during I/R, and probably, the associated cell dysfunction, through their central role in cellular bioenergetics. (C) 2003 Elsevier Science B.V. All rights reserved.