THE immunosuppressive agent FK 506 has been investigated for its adverse effects on the liver, kidney, and the pancreas. I FK 506, however, has multiple biological effects which may be beneficial for the liver. For instance, pretreatment of rats with FK 506 has been shown to both protect the liver from ischemic injury2 and to ameliorate the hepatic injury associated with ischemia and reperfusio...

Using a rat model, the effect of pre-treatment with FK 506 on hepatic ischemia/reperfusion injury was investigated. All control animals died within 72 h of the ischemia/reperfusion injury. Pre-treatment of the animals with FK 506 (0.3 mg/kg in 0.5 ml saline) administered intravenously improved survival. The most striking protection against fatal ischemia/reperfusion injury was achieved in rats ...

OBJECTIVES Calcineurin (CN) is a main phosphatase and a critical regulator of cellular pathways for learning, memory, and plasticity. The FK-506 (tacrolimus), a phosphatase inhibitor, is a fungal-derived agent and a common immune suppressant extensively used for tissue transplantation. To further clarify the role of CN in different stages of learning and memory the main aim of this study was to...

FK 506 is a macrolide antibiotic with powerful immunosuppressive activities. It is known to prevent allograft rejection in rats, dogs, monkeys, baboons, and humans. 1.2 In vitro studies indicate that, like cyclosporine (Cy A), FK 506 acts specifically by inhibiting the transcription of a limited set of early T-cell activation genes, including those encoding interleukin-2 (IL-2), IL-3, IL-4, and...

FK 506 is a macrolide with potent immunosuppressive effects. Its immunosuppressive property has been documented in both in vitro! lymphocyte proliferation studies and in vivo studies. FK 506 treatment significantly prolongs graft survival in rats receiving heterotopic heart transplants. dogs receiving kidneys or livers. and baboons receiving kidney transplants.2 Currently, FK 506 is undergoing ...

FK-506, a widely used immunosuppressant, has caused a few clinical cases with QT prolongation and torsades de pointe at high blood concentration. The proarrhytmogenic potential of FK-506 was investigated in single rat ventricular cells using the whole cell clamp method to record action potentials (APs) and ionic currents. Fluorescence measurements of Ca2+ transients were performed with indo-1 A...

FK 506 HAS HAD A major beneficial effect on the survival of transplanted organs. However. the use of FK 506 is limited by its toxicity. To circumvent this problem. we attempted to amplify the therapeutic efficacy of lowdose FK 506 bv the combined use of various antimetabolites, including' RS-61443 (RS),1 mizoribine (MIZ),2 and azathioprine (AZA). Therapeutic interaction was evaluated with rat a...

In order to mediate their effects, cyclosporin A and FK-506 must each bind with high affinity to a cytosolic target protein that belongs to the immunophilin group. FK-506 forms complexes with the FK-506 binding protein FKBP, mainly FKBP-12, and these complexes possess immunosuppressive activity through their ability to interact with another target, the abundant serine threonine phosphatase calc...

The detrimental effects of hypoxic damage to central nervous system lead to energy depletion, free radical formation, lipid peroxidation (LPO), and increased calcium. We hypothesized that in vitro tacrolimus (FK-506) and cyclosporine A (CsA) could be protective against hypoxic damage in spinal cord. Dorsal columns were isolated from the spinal cord of adult rats and injured by exposure to hypox...

WITH the use of Cy A for clinical liver transplantation, I-year survival rates have approached 70%. Nevertheless, allograft rejection continues to be the most common cause of retransplantation and death. Clinical rejection occurs in 70% ofliver allograft recipients on CyA and steroid therapy. 1 In addition, nephrotoxicity is the principal and dose-limiting side effect of Cy A. Chronic renal dam...