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The ventral anterior nucleus of the thalamus (VATh) gathers motor information from the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNpr) of the basal ganglia and projects directly to motor areas of cortex. GPi/SNpr send their tonically active gamma-aminobutyric acid (GABA)ergic outputs to VATh. The abnormal firing patterns of GABAergic neurons in GPi/SNpr lead to motor deficits. In Parkinson's disease, the spontaneous firing pattern of GPi/SNpr neurons is abnormal due to the degeneration of the nigrostriatal dopaminergic pathway. In a previous study, we found that systemically administered vasoactive intestinal peptide (VIP) was effective at reversing the motor deficits (but not the decline in striatal dopamine levels) in a rat model of Parkinson's disease (6-hydroxydopamine (6-OHDA) exposure). In addition to the beneficial effects on the motor response, VIP could also attenuate both neuronal cell death and the characteristic loss of the myelin sheath that is associated with 6-OHDA administration into the rat striatum. VIP was thought to preserve neurons by inducing native brain mast cells to adopt a nondegranulating phenotype that had the ability to secrete numerous neuroprotective substances, such as nerve growth factor (NGF) and heparin. In the present study, the effect of systemically administered VIP (25 ng/kg i.p.) was investigated on GABA levels of the VATh, dopamine/3,4-dihydroxyphenylacetic acid (DOPAC) levels in the corpus striatum, and the NGF, rat mast cell protease II (RMCPII), serotonin, and heparin content of brain mast cells in 6-OHDA-lesioned rats. Extracellular concentrations of GABA, dopamine, and DOPAC were measured by microdialysis and high-performance liquid chromatography. NGF, RMCPII, serotonin, and heparin levels were examined by immunohistochemical staining techniques. A total of 48 young adult Sprague-Dawley rats were used in the study, and these were assigned to one of six groups. Unilateral injection of 6-OHDA, 2 microl (6 mg/microl), was made into the right corpus striatum. VIP-treated animals received 25 ng/kg VIP i.p. at 2-day intervals for a period of 15 days. The present results demonstrated that VIP significantly increased the levels of GABA in the VATh that were reduced by 6-OHDA application and increased the number of NGF-immunoreactive mast cells but did not alter dopamine metabolism. Therefore, the protective effect of VIP on motor function is possibly related to the increased levels of GABA in the VATh, and its neuroprotective actions may be mediated by the release of NGF from brain mast cells.

The anticancer drug cyclophosphamide (CP) has nephrotoxic effects besides its urotoxicity, which both in turn limit its clinical utility. The nephrotoxicity of CP is less common compared to its urotoxicity, and not much importance has been given for the study of mechanism of CP-induced nephrotoxicity so far. Overproduction of reactive oxygen species (ROS) during inflammation is one of the reasons of the kidney injury. Selenoproteins play crucial roles in regulating ROS and redox status in nearly all tissues; therefore, in this study, the nephrotoxicity of CP and the possible protective effects of seleno L-methionine (SLM) on rat kidneys were investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats each. The control group received saline, and other rats were injected with CP (100 mg/kg), SLM (0.5 or 1 mg/kg), or CP+ SLM intraperitoneally. Malondialdehyde (MDA) and glutathione (GSH) levels in kidney homogenates of rats were measured, and kidney tissues were examined under the microscope. CP-treated rats showed a depletion of renal GSH levels (28% of control), while CP+SLM-injected rats had GSH values close to the control group. MDA levels increased 36% of control following CP administration, which were significantly decreased after SLM treatment. Furthermore, these biochemical results were supported by microscopical observations. In conclusion, the present study not only points to the therapeutic potential of SLM in CP-induced kidney toxicity but also indicates a significant role for ROS and their relation to kidney dysfunction.