Differential expression of cytoprotective and apoptotic genes in an ischaemia-reperfusion isolated organ perfusion model of the transplanted kidney.

The optimal kidney preservation system and methods to ameliorate reperfusion injury are major factors in accomplishing successful graft function following transplantation. Ischaemia and reperfusion lead to cellular stress and the adaptive response may include the activation of genes involved in cellular protection and/or cell death by apoptosis. We investigated the expression of cytoprotective heme oxygenase-1 (HO-1), anti-apoptotic Bcl-2 and pro-apoptotic Bax after 6 h isolated organ perfusion in porcine kidneys that had been given 10 and 40 min warm ischaemic time.

The experimental agent pirfenidone reduces pro-fibrotic gene expression in a model of tacrolimus-induced nephrotoxicity.

Background: Tacrolimus nephrotoxicity is thought to contribute to renal allograft dysfunction and subsequent failure, a process that is underpinned by alterations in mRNA expression of genes involved in matrix metabolism. The new anti-fibrotic pirfenidone was tested for its potential to reverse markers of renal dysfunction.

Materials And Methods: Rats were salt-depleted before tacrolimus and pirfenidone treatment.

Differential effects of modern immunosuppressive agents on the development of intimal hyperplasia.

Modern immunosuppressive agents such as tacrolimus and rapamycin are claimed to be associated with a reduction in vascular narrowing, a central feature of chronic rejection. This study assesses the effect of cyclosporine, tacrolimus and rapamycin on the development of intimal thickening, fibrosis-associated genes and deposition of extracellular matrix (ECM) proteins in a model of intimal hyperplasia. Male Sprague-Dawley rats received either no treatment or 5 mg/kg cyclosporine, 0.

The effect of combined rapamycin/cyclosporine on the changes in pro-fibrotic gene expression that occur during the development of allograft vasculopathy in rats, compared with cyclosporine or rapamycin in isolation.

Chronic allograft dysfunction, the leading cause of solid-organ transplant failure, is characterised by histological evidence of extracellular matrix (ECM) accumulation (fibrosis). The aim of this study was to compare the effect of combined rapamycin and cyclosporine therapy on fibrosis-associated gene expression and ECM turnover during the development of allograft vasculopathy, compared with either agent alone. Lewis recipients of F344 rat thoracic-to-abdominal aorta transplants were administered rapamycin, cyclosporine, combined rapamycin and cyclosporine or no treatment.