Anti-Apoptotic Effects of Dapsone After Spinal Cord Injury in Rats.

Spinal cord injury (SCI) is a condition producing irreversible damage to the neurological function. Among the leading mechanisms associated to cell death after SCI, excitotoxicity, oxidative stress, inflammatory response and apoptosis are considered potential targets to prevent tissue damage. We recently reported that dapsone an anti-inflammatory drug, decreases the activity of myeloperoxidase, lipid peroxidation, improve neurological function and increase the amount of spared tissue after SCI in rats. In this study, we characterized the anti-apoptotic effect of dapsone administered at 12.5 mg/kg/24 h dose, starting at 3 and 5 h after SCI. We monitored the activity of caspases-8, 9, and 3 and quantitated Annexin V and TUNEL positive cells in the core of the lesion. Results showed increased activities of caspase-8, 9 and 3 at 72 h by SCI to reach increments of 69, 143 and 293 %, respectively, as compared to sham group. Meanwhile, dapsone, administered at 3 and 5 after SCI, reduced caspase-8 activity by 36 and 44 % respectively, whereas the activity of caspase-9 was diminished by 37 %. Likewise, the activity of caspase-3 showed a decrease of 38 %. Finally, both Annexin V and TUNEL-positive cells were significantly reduced by DDS as compared to untreated SCI animals. Results showed that dapsone exerted anti-apoptotic effect after SCI.

Antioxidant, anticonvulsive and neuroprotective effects of dapsone and phenobarbital against kainic acid-induced damage in rats.

Excitotoxicity due to glutamate receptors (GluRs) overactivation is a leading mechanism of oxidative damage and neuronal death in various diseases. We have shown that dapsone (DDS) was able to reduce both neurotoxicity and seizures associated to the administration of kainic acid (KA), an agonist acting on AMPA/KA receptors (GluK1-GluK5). Recently, it has been shown that phenobarbital (PB) is also able to reduce epileptic activity evoked by that receptor. In the present study, we tested the antioxidative, anticonvulsive and neuroprotective effects of DDS and PB administered alone or in combination upon KA toxicity to rats. Results showed that KA increased lipid peroxidation and diminished reduced glutathione (GSH), 24 h after KA administration and both drugs in combination or individually inhibited these events. Likewise, KA promotes mortality and this event was antagonized by effect of both treatments. Additionally, the behavioral evaluation showed that DDS and PB administered alone or in combination decreased the number of limbic seizures and reduced the percentage of animals showing tonic-clonic seizures versus the control group, which was administered only with KA. Finally, our study demonstrated that all of the treatments prevented the neuronal death of the pyramidal cell layer of hippocampal CA-3. In conclusion, the treatment with DDS and PB administrated alone or in combination exerted antioxidant, anticonvulsive and neuroprotective effects against the neurotoxicity induced by KA in rats, but their effects were not additive. Thus, it may be good options of treatment in diseases such as epilepsy and status epilepicus, administered separately.

Enhancement of Heat and Mass Transfer in the DCMD Process Using UV-Assisted 1-Hexene-Grafted PP Membranes.

The two main challenges for industrial application of membrane distillation (MD) are mitigation of temperature polarization and reduction of high-energy consumption. Despite the development of advanced materials and the configuration improvements of MD units, membrane surface modification is still one of the alternatives to overcome temperature polarization and improve membrane performance. This work reports a novel and simple method to modify the physical and chemical properties of the polypropylene membrane in order to improve its performance in direct contact membrane distillation (DCMD). The membrane was grafted by polymerization with 1-hexene, UV irradiation, and benzophenone as a photoinitiator. A grafting degree of up to 41% was obtained under UV irradiation for 4 h. The performance of the modified membrane in DCMD was evaluated at different temperatures and salt concentrations in the feed. First, it was found that there was an increase of the vapor permeate flux in the MD process within the range of tested temperatures and salt concentrations. The results were analyzed in terms of the physical properties of the membrane, the transport phenomena, and the thermal efficiency of the process. Theoretical analysis of the results indicated that grafting increased the transfer coefficients of mass and heat of the membrane. Hence, it improved the membrane performance and the thermal efficiency of the DCMD process.

Metallothionein-I + II Reduces Oxidative Damage and Apoptosis after Traumatic Spinal Cord Injury in Rats.

After spinal cord injury (SCI), some self-destructive mechanisms start leading to irreversible neurological deficits. It is known that oxidative stress and apoptosis play a major role in increasing damage after SCI. Metallothioneins I and II (MT) are endogenous peptides with known antioxidant, neuroprotective capacities. Taking advantage of those capacities, we administered exogenous MT to rats after SCI in order to evaluate the protective effects of MT on the production of reactive oxygen species (ROS) and lipid peroxidation (LP), as markers of oxidative stress. The activities of caspases-9 and -3 and the number of annexin V and TUNEL-positive cells in the spinal cord tissue were also measured as markers of apoptosis. Rats were subjected to either sham surgery or SCI and received vehicle or two doses of MT (10 µg per rat) at 2 and 8 h after surgical procedure. The results showed a significant increase in levels of MT protein by effect of SCI and SCI plus treatment at 12 h, while at 24 h an increase of MT was observed only in the injury plus treatment group (p < 0.05). ROS production was decreased by effect of MT in lesioned tissue; likewise, we observed diminished LP levels by MT effect both in the sham group and in the group with SCI. Also, the results showed an increase in the activity of caspase-9 due to SCI, without changes by effect of MT, as compared to the sham group. Caspase-3 activity was increased by SCI, and again, MT treatment reduced this effect only at 24 h after injury. Finally, the results of the number of cells positive to annexin V and TUNEL showed a reduction due to MT treatment both at 24 and 72 h after the injury. With the findings of this work, we conclude that exogenously administered MT has antioxidant and antiapoptotic effects after SCI.

Activation of heme oxygenase recovers motor function after spinal cord injury in rats.

Characterization of auto-destructive mechanisms, leading to cell death after spinal cord injury (SCI) is important to prevent further damage to tissue. Heme oxygenase (HO) catalyzes the oxidation of heme to biliverdin and carbon monoxide (CO), as a response to cell damage. Products of HO action have biological effects, as antioxidant biliverdin. We evaluated the changes of HO activity after injury, and the effect of pharmacological treatments with hemin (an inducer) and (Sn)-protoporphyrin (an inhibitor, Sn-PPIX) of HO, upon motor recovery after SCI. Female Wistar rats were submitted to SCI by trauma and sacrificed at several times (2, 4, 8, 12 and 24h) after injury to evaluate HO activity. Additional groups of rats were treated with either hemin or Sn-PPIX, to evaluate motor recovery, spared spinal cord tissue and HO activity. Results showed that HO control activity was increased by effect of SCI, at all times evaluated, as compared to sham group values. Twenty-four hours after injury, HO activity was increased 7.2-fold by hemin treatment, as compared to SCI plus vehicle group values. In addition, animals treated with hemin 2 and 8h after SCI, showed a better motor recovery and higher spared cord tissue, as compared to control group values. Our findings indicate that activation of HO is a beneficial mechanism when attained during the acute phase after SCI.