It

has been reported that CsA binds to cyclophilin D and prevents opening of mitochondrial transition pore (Mbye et al. 2008; Panickar et al. 2009). However, the exact mechanism by which FK-506 and CsA exert their ROS-scavenging potential is not well understood yet. Hypoxia results in Hedgehog inhibitor tissue damage as observed by white patches in gray and white matter. FK-506 and CsA treatment showed significant reduction of white patches, which confers less tissue damage and increase viability. FK506 was, however, more effective over CsA in reducing white patches. On the basis of the findings above, it could be speculated that FK-506 and CsA inhibited ROS-mediated mitochondrial swelling and restored ATP synthesis, as evidenced Inhibitors,research,lifescience,medical by the decrease in mitochondrial swelling Inhibitors,research,lifescience,medical and restoration of ATP content and reduction in the tissue damage as observed by TTC staining. The present results suggested that ROS culminate in irreversible secondary damage in the spinal cord. Independent treatment with FK-506 and CsA showed neuroprotective effect against ROS-mediated mitochondrial dysfunctions. Further studies on combinatorial effect of CsA and FK-506 may provide a more effective strategy in the

management of Inhibitors,research,lifescience,medical ROS-mediated secondary neuronal damage in spinal cord.
Polyneuropathy is a neurological disorder that is common in middle and late adulthood. Estimates of its prevalence range from 2.4% to 8% and depend on the selection of patients, that is, general population or hospital series,

and is even higher in individuals exposed to various toxins, or patients with diabetes mellitus (Beghi et al. 1995). Although there are several Inhibitors,research,lifescience,medical known causes of polyneuropathy, the etiology often remains unknown (Martyn and Hughes 1997) and is then labeled cryptogenic. The mechanism in those cases is often considered to be exposure to occupational Inhibitors,research,lifescience,medical or environmental agents, which we have previously investigated (Tondel et al. 2006). Axonopathy is the most common form of pathology in toxic neuropathies, but underlying pathologic mechanisms are unclear. It is believed that failure of axonal transport results in degeneration of vulnerable distal Ketanserin nerve segments (Spencer et al. 1979; Griffin and Watson 1988) and when the process continues, the degeneration proceeds proximally towards the cell body. In industrial settings and the general environment, some compounds are neurotoxic, and frequently affect the peripheral nerve (Spencer and Schaumburg 2000). One example is n-hexane, which accumulates in nerve tissue during chronic exposure (Feldman 1999). It is known to cause primary axonal degeneration with secondary demyelination (Chang et al. 1993). Biotransformation of exogenous and endogenous compounds may play a role in individual susceptibility due to the genetic variability of enzymes involved in detoxification. The metabolism of biotransformation can be divided into two phases.