Effect of ligustrazine on ischemia-reperfusion injury in murine kidney.
BACKGROUND
Ischemia-reperfusion (I/R) injury is unavoidable in cadaveric renal transplantation. It contributes to acute rejection and chronic allograft dysfunction. Studies have shown that Ligustrazine, a purified and chemically identified component of a Chinese herbal remedy, is a potent blocker of vasoconstriction and has strong effects to scavenge oxygen free radicals. Since warm I/R is potentially more damaging than cold storage, we investigated the possible protective effect of Ligustrazine on warm I/R in mice.


METHODS
Unilaterally nephrectomized C57BL/6 male mice were subjected to 50 minutes of left renal ischemia. Group I were sham-operated animals; group II, nontreated animals (saline, iP 30 minutes before I/R); and group III, Ligustrazine-treated animals (80 mg/kg, iP 30 minutes before I/R). Mice were sacrificed 24 hours postreperfusion. Serum creatinine, blood urea nitrogen, kidney malondialdehyde (MDA)level, and superoxide dismutase (SOD) were determined as well as examining the kidneys histologically with immunohistochemistry for Bcl-2, and ICAM-1.


RESULTS
I/R produced a six fold increase in creatinine and urea nitrogen levels in group II. Ligustrazine halved the increase, as well as attenuated the necrosis and apoptosis in the tubules (P < .01). Ligustrazine decreased MDA levels and ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated following I/R, especially in the Ligustrazine-treated group (P < .01). The up-regulation of ICAM-1 was greatly diminished by Ligustrazine (P < .01).


CONCLUSIONS
These findings suggest that Ligustrazine reduces the renal dysfunction associated with warm I/R of the kidney.
Feng
L
L
Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, People's Republic of China. feng31@sohu.com
Xiong
Y
Y
Cheng
F
F
Zhang
L
L
Li
S
S
Li
Y
Y
D000818:Animals; D001806:Blood Urea Nitrogen; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009392:Nephrectomy; D011719:Pyrazines / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D014665:Vasodilator Agents / Q000627:therapeutic use*
D011719:Pyrazines; D014665:Vasodilator Agents; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C017953:tetramethylpyrazine