Effects of diamide and iodoacetamide on the expression of the glycoprotein IIb/IIIa complex on blood platelets

We have examined the effects of two agents that alter platelet thiol-disulphide status on platelet aggregation and on the ability of platelets to bind a monoclonal antibody (M148) that is directed toward an epitope on the glycoprotein IIb/IIIa complex. The immediate effect of both diamide and iodoacetamide is to enhance aggregation but after further incubation diamide, but not iodoacetamide, inhibits platelet aggregation. Incubation of platelets with diamide, but not iodoacetamide, is accompanied by a marked increase in the amount of M148 that binds to platelets. This is presumably a reflection of an altered distribution of glycoproteins on the platelet surface. It is known that diamide, but not iodoacetamide, leads to polymerisation of cytoskeletal proteins in platelets. Thus evidence is provided that agents that interact with the cytoskeleton inhibit platelet behaviour via an effect on surface glycoproteins.     

Extracellular ADP prevents neuronal apoptosis via activation of cell antioxidant enzymes and protection of mitochondrial ANT-1

Apoptosis in neuronal tissue is an efficient mechanism which contributes to both normal cell development and pathological cell death. The present study explores the effects of extracellular ADP on low [K⁺]-induced apoptosis in rat cerebellar granule cells. ADP, released into the extracellular space in brain by multiple mechanisms, can interact with its receptor or be converted, through the actions of ectoenzymes, to adenosine. The findings reported in this paper demonstrate that ADP inhibits the proapoptotic stimulus supposedly via: i) inhibition of ROS production during early stages of apoptosis, an effect mediated by its interaction with cell receptor/s. This conclusion is validated by the increase in SOD and catalase activities as well as by the GSSG/GSH ratio value decrease, in conjunction with the drop of ROS level and the prevention of the ADP protective effect by pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), a novel functionally selective antagonist of purine receptor; ii) safeguard of the functionality of the mitochondrial adenine nucleotide-1 translocator (ANT-1), which is early impaired during apoptosis. This effect is mediated by its plausible internalization into cell occurring as such or after its hydrolysis, by means of plasma membrane nucleotide metabolizing enzymes, and resynthesis into the cell. Moreover, the findings that ADP also protects ANT-1 from the toxic action of the two Alzheimer's disease peptides, i.e. Aβ1–42 and NH₂htau, which are known to be produced in apoptotic cerebellar neurons, further corroborate the molecular mechanism of neuroprotection by ADP, herein proposed.     

Effectiveness of low-power laser therapy in improvement of the peripheral neuropathy induced by xenobiotics in rats

BackgroundPeripheral neuropathy (PN) is the damage and dysfunction of neurons of the peripheral nervous system. The present study was conducted to estimate the effectiveness of low-power laser therapy (LPLT) in the management of PN in a rats’ model.MethodsPN was induced by giving dichloroacetate (DCA) (250 mg/kg/day) for up to 12 weeks. Four groups of rats were used: control group, PN group, PN group treated with gabapentin and PN group treated with LPLT. The study was conducted for 8 weeks. The management of PN was estimated by behavioral tests which included hot plate and Morris water maze tests. Blood biochemical analysis were carried out.ResultsUsing of hot plate test indicated thermal hypoalgesia and using Morris water maze test showed cognitive decline in PN rats. Treatment with LPLT or gabapentin improved both the pain sensations and deteriorated memory that occurred in the PN rats. Biochemical analysis showed that LPLT significantly decreased the elevated beta-endorphin level in PN rats, while gabapentin could not reduce it. Treatment PN rats with LPLT or gabapentin shifted the high levels of TNF-α, IL-1β and IL-10 cytokines back to their normal values. Serum nitric oxide and MDA significantly increased in the PN group together with significant reduction in the rGSH level, these values were significantly improved by LPLT application while this was not the case with gabapentin treatment. Furthermore, treatment with gabapentin or LPLT significantly reduced serum ALAT and ASAT activities which are otherwise increased in the PN group. S100B, PGE2, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, urea and creatinine showed insignificant changes among all groups.ConclusionsOur results showed that treatment with LPLT is more efficient than gabapentin in ameliorating the peripheral neuropathy induced by xenobiotics.