succimer and Inflammation

Lead (Pb) toxicity is one of the most prevalent causes of human neurotoxicity. The available chelator drugs used now have many adverse effects. So, in this study, the protective role of Beta vulgaris juice (BVJ) on rat neurotoxicity induced by Pb was evaluated and the results were compared with the results of dimercaptosuccinic acid (DMSA, as used drug). Additionally, the synergistic effect of BVJ and DMSA against Pb-induced neurotoxicity was assessed. The study focused on the determination of the antioxidant, anti-inflammatory, and neurological potential of BVJ (alone, and with DMSA) towards lead-induced neurotoxicity. Also, the characterization of BVJ was studied. The results showed that BVJ contains considerable quantities of polyphenols, triterpenoids, and betalains which play an important role as antioxidants and anti-inflammatory. BVJ exhibited a protective effect against neurotoxicity via the reduction of Pb levels in blood and brain. Moreover, BVJ decreased the oxidative stress, inflammation, and cell death induced by Pb. Also, BVJ regulated the activities of acetylcholine esterase and monoamine oxidase-A which changed by Pb toxicity. BVJ and DMSA combination displayed a synergistic antineurotoxic effect (combination index ˂ 1). These results were in harmony with brain histopathology. Conclusion: BVJ has a powerful efficacy in the protection from brain toxicity via diminishing Pb in the brain and blood circulation, resulting in the prevention of the oxidative and inflammatory stress. Treatment with BVJ in combination with DMSA revealed a synergistic effect in the reduction of neurotoxicity induced by Pb. Also, the antioxidant and anti-inflammatory effects of the BVJ lead to the improvement of DMSA therapy.

Topics: Animals; Antioxidants; Beta vulgaris; Brain; DNA Fragmentation; Drug Synergism; Inflammation; Lead; Male; Neuroprotective Agents; Neurotoxicity Syndromes; Oxidative Stress; Plant Extracts; Rats; Succimer

Lead (Pb) is observed in all areas of the environment, mainly derived from human operations such as mining, processing, and burning fossil fuels. Pb toxicity is one of the most prevalent causes of human hepatotoxicity. The available chelator drugs used now have many adverse effects and therefore the world is looking for natural and secure alternatives.. Here, we evaluated the hepatoprotective role of the oral administration (1 g/kg b.w.) of the lyophilized Beta vulgaris juice (BVJ) against Pb-induced rat hepatotoxicity. We also examined the possible synergistic hepatoprotective impact of the combination between BVJ and 2,3- dimercaptosuccinic acid (DMSA, the currently approved drug for Pb-toxicity). The evaluation depends on the ability of BVJ, DMSA, or their combination (BVJ-DMSA) to reduce serum and hepatic Pb level and to avoid oxidative stress and inflammation caused by Pb. The level of lipid peroxidation, reduced glutathione (GSH), total antioxidant capacity, and the activity of the antioxidant enzymes were quantified. In addition, the level of interleukin (IL)-6, nitric oxide (NO), DNA fragmentation, and liver histology were studied.. The results showed that BVJ contained considerable amounts of betalains, vitamin C, and various types of phenolic compounds. Therefore, BVJ displayed a significant (p < 0.05) preventive influence on the elevation of Pb levels in blood and liver as well as the hepatic DNA fragmentation. In addition, it significantly (p < 0.05) improved most of the studied antioxidant and inflammatory markers in the Pb-intoxicated rats. However, the combined extract (BVJ-DMSA) revealed synergistic (combination index < 1) activities in most of the tested parameters. The histopathological results verified the biochemical findings of this research.. BVJ has a potent efficiency in the protection from Pb-induced hepatotoxicity through the reduction of its accumulation in blood and liver and the prevention of the oxidative stress and inflammation induced by Pb. Additionally, the treatment of hepatotoxicity with BVJ and DMSA in combination showed a synergistic effect and reduced the adverse effects induced by DMSA. Thus, BVJ can be a promising hepatoprotective extract against lead toxicity and its combination with DMSA potentiates this effect.

Topics: Administration, Oral; Animals; Antioxidants; Beta vulgaris; Chelating Agents; Disease Models, Animal; Drug Synergism; Egypt; Fruit and Vegetable Juices; Inflammation; Lead; Lead Poisoning; Liver; Male; Oxidative Stress; Rats; Succimer

Iron oxide nanoparticles (IONPs) are promising neuroimaging agents and molecular cargo across neurovascular barriers. Development of intrinsically safe IONP chemistries requires a robust in vivo nanoneurotoxicity screening model. Herein, we engineered four IONPs of different surface and core chemistries: DMSA-Fe2O3, DMSA-Fe3O4, PEG-Fe3O4 and PEG-Au-Fe3O4. Capitalizing on the ability of the peripheral nervous system to recruit potent immune cells from circulation, we characterized a spatiotemporally controlled platform for the study of in vivo nanobiointerfaces with hematogenous immune cells, neuroglial and neurovascular units after intraneural IONP delivery into rat sciatic nerve. SQUID magnetometry and histological iron stain were used for IONP tracking. Among the IONPs, DMSA-Fe2O3 NPs were potent pro-apoptotic agents in nerve, with differential ability to regulate oxidative stress, inflammation and apoptotic signaling in neuroglia, macrophages, lymphocytes and endothelial cells. This platform aims to facilitate the development of predictive paradigms of nanoneurotoxicity based on mechanistic investigation of relevant in vivo bio-nanointerfaces.. This team of investigators report the development of a platform that enables screening of iron oxide nanoparticles from the standpoint of their potential neurotoxicity, utilizing rat sciatic nerves. Such screening tools are clearly needed with the potential advent of iron oxide nanoparticle-based diagnostic and therapeutic approaches.

Topics: Animals; Antioxidants; Apoptosis; Chemical Phenomena; Female; Inflammation; Magnetite Nanoparticles; Neurotoxins; Oxidative Stress; Phenotype; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Signal Transduction; Succimer; Surface Properties

The present study evaluated 99mTc(V) DMSA as an agent for the visualization of inflammatory lesions in comparison to 99mTc(III) DMSA and 99mTC-HIG. All three radiopharmaceuticals were prepared with commercial kits. 99mTc(V) DMSA was prepared at neutral pH by the addition of first bicarbonate and then pertechnetate to the kit contents. The labeling efficiency was 99% as determined by ITLC. Abscesses were induced by i.m. injection of 50 microliters turpentine into the right thighs of 36 Swiss albino mice. Six days later 3.7 MBq of each radiopharmaceutical was i.v. administered to 12 mice. The mice were sacrificed at 1, 3, 6 and 24 h later. Scintigrams were obtained with a gamma camera. The abscesses were better visualized on scintigrams with 99mTc(V) DMSA compared to 99mTc(III) DMSA, starting at 1 h. The animals were dissected and the organs were removed, weighed and the radioactivity determined with a gamma counter. The abscess to other tissue ratios were higher with 99mTc(V) DMSA than the other radiopharmaceuticals. The max. abscess/muscle ratios were 9.46 +/- 3.20 (24 h), 4.19 +/- 1.39 (6 h) and 5.98 +/- 1.17 (24 h) and max. abscess/blood ratios were 6.22 +/- 1.41, 4.09 +/- 0.84 and 0.914 +/- 0.351 all at 24 h for 99mTc(V) DMSA, 99mTc(III) DMSA and 99mTc-HIG, respectively. Experimental arthritis was produced in New Zealand white rabbits by intra-articular injection of ovalbumin. Four days later 37 MBq of 99mTc(V) DMSA and 99mTc-HIG were each i.v. administered to 3 rabbits. Scintigrams obtained at 1, 3, 6, and 24 h clearly demonstrated arthritic joints. ROI's over arthritic joints were compared to contralateral normal joints (A/C). The max. A/C ratios were 2.10 +/- 0.31 (3 h) and 2.92 +/- 0.99 (24 h) for 99mTc(V) DMSA and 99mTc-HIG, respectively. Our results indicated the feasibility of imaging inflammatory lesions with 99mTc(V) DMSA.

Topics: Abscess; Animals; Arthritis; Evaluation Studies as Topic; Immunoglobulins; Inflammation; Mice; Organotechnetium Compounds; Rabbits; Radionuclide Imaging; Radiopharmaceuticals; Succimer; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid; Tissue Distribution