Effect of ligustrazine on chronic allograft nephropathy in rats

Our previous study demonstrated that Ligustrazine reduced renal dysfunction associated with ischemia-reperfusion injury in mice. In this study, we investigated whether Ligustrazine herbal injection had any preventive and therapeutic effectiveness against chronic allograft nephropathy in rats.

Male Lewis rats that received left renal grafts from male Fisher 344 rats were randomly divided into five groups: group A only received cyclosporine (CsA; 10 mg.kg(-1).d(-1)) every day. Groups B, C, and D received low-dose Ligustrazine (50 mg.kg(-1).d(-1))+CsA (10 mg.kg(-1).d(-1)); high-dose Ligustrazine (100 mg.kg(-1).d(-1))+CsA (10 mg.kg(-1).d(-1)); and CsA (10 mg.kg(-1))+mycophanolate mofetil (10 mg.kg(-1).d(-1)), respectively. Group E was an isografted group (Fisher 344 to Fisher 344). Grafts were preserved in 4 degrees C University of wisconsin solution for 1 hour prolonged cold ischemia. All recipient animals were unilaterally right nephrectomized. Serum creatinine (Scr), blood urea nitrogen (BUN), urinary protein, kidney malondialdehyde (MDA) level, and superoxide dismutase (SOD) were determined, as well as examining kidney histology with immunohistochemistry for Bcl-2, and ICAM-1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested to show whether Ligustrazine has side effects.

Compared with group E, ischemia and rejection produced a ninefold increase in GSR and Banff score, as well as significant increases of Scr, BUN, and urinary protein levels in group A. High doses of Ligustrazine significantly slowed the increase (P<.01). Ligustrazine also decreased MDA levels and ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated posttransplantation, especially in the Ligustrazine-treated group (P<.01). The up-regulation of ICAM-1 was greatly diminished by Ligustrazine (P<.01). Furthermore, there was little difference in ALT/AST between the Ligustrazine-treated and the isograft group.

These findings suggested that Ligustrazine could postpone chronic renal allograft dysfunction associated with cold ischemia injury and chronic allograft rejection but had no evident hepatic side effects.