This study was designed to assess the effect of spinal cord injury on neurobehavioral, electrophysiological, structural, and biochemical changes in normal and diabetic rats. Experimental diabetes was induced in Sprague-Dawley male rats (weighing 250-280 g) with streptozotocin (50 mg/kg i.p.). Eight weeks after the treatment with streptozotocin the animals were anaesthetized with chloral hydrate and laminectomy was performed at T 7-8 level leaving the dura intact. A compression plate (2.2 x 5.0 mm) loaded with a weight of 35 g was placed on the exposed spinal cord for 5 min. Postoperative neurological function was assessed using inclined plane test, modified Tarlov score, and vocal and sensory score daily for 10 days. Electrophysiological changes were assessed using somatosensory and corticomotor evoked-potentials. The animals were sacrificed at different time intervals and injured site of the spinal cord was analyzed for changes in vitamin E and glutathione levels (as markers of oxidative stress). Pathological changes in spinal cord were also studied using light microscopy. The data on neurobehavioral study clearly indicated that the compression of spinal cord produced highly significant neurological deficit and poor recovery in diabetic rats as compared to nondiabetic rats. Our histopathological and electrophysiological results also confirmed that diabetic animals are more susceptible to compressive spinal cord injury as compared to nondiabetic animals. A higher depletion of antioxidant defense markers (vitamin E and glutathione) was observed in diabetic rats as compared to nondiabetic rats. These results point toward the role of free radicals in poor recovery in diabetic rats following neurotrauma. Further studies are warranted to assess the neuroprotective potential of antioxidants to retard the secondary pathophysiological events following neurotrauma and to enhance the recovery.
The biochemical mechanism underlying cyclosporine (CsA)* induced nephrotoxicity is far from clear. Increased generation of oxygen derived free radicals (ODFR) and enhanced activity of phospholipase A2 (PLA2) have been observed in experimental animals following treatment with CsA. Several recent reports have shown that quinacrine, besides being a potent inhibitor of PLA2, suppresses the generation of ODFR. The present study was designed to investigate the effect of quinacrine on CsA induced nephrotoxicity in rats. Male Wistar rats (weighing 280-300 g) were randomized into eight groups of eight animals each. Group 1 (control) received appropriate vehicles only, whereas the rats in groups 2, 3, 4, and 5 received subcutaneous injection of CsA (17.5 mg/kg dissolved in olive oil) daily for 8 weeks. The animals in groups 3, 4, and 5 were also given intraperitoneal injections of quinacrine in three different doses of 2.5 mg/kg, 5 mg/kg, and 10 mg/kg body weight, respectively, in addition to CsA. The animals in groups 6, 7, and 8 received intraperitoneal injection of quinacrine alone at doses of 2.5 mg/kg, 5 mg/kg, and 10 mg/kg respectively for eight weeks. After 8 weeks, animals were sacrificed under light ether anesthesia and blood and kidney samples were collected for various biochemical and histological studies. The biochemical parameters included blood urea nitrogen (BUN), serum creatinine (Scr), potassium, and sodium. The blood was also analyzed for the level of CsA. The kidney samples were analyzed for malondialdehyde (MDA), glutathione, and vitamin E (VE). Kidney sections were prepared for histopathological studies using hematoxylin-eosin staining. There was an increase in BUN, Scr, and potassium levels and decrease in sodium levels in cyclosporine alone treated group, suggesting a significant nephrotoxicity. Quinacrine treatment significantly protected animals against CsA induced biochemical changes. Our studies on free radical indices showed that quinacrine treatment protected animals against cyclosporine induced increase in MDA and depletion of glutathione and VE. The beneficial effect of quinacrine against CsA induced nephrotoxicity was also confirmed by histological studies.
In order to assess the effects of the fungal toxin wortmannin on the immune system, rats and mice were fed wortmannin-containing cultures of Fusarium oxysporum for 1 or 2 weeks. Wortmannin caused significant decreases in thymic weight, thymic lymphocyte numbers, serum IgG and IgM levels, the primary humoral response to T-dependent and T-independent antigens and the proliferative response of spleen cells to pokeweed mitogen. In vitro administration of wortmannin did not produce evidence of cytotoxicity to spleen or thymus cells. The data indicate that wortmannin inhibits immune function in rats and mice and suggest that metabolic modification of the toxin is necessary for toxicity.
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