Effects Of Sodium Para-aminosalicylic Acid On Metal Elements,Learning And Memory And Hippocampal Ultramicro-structure In Manganese-exposed Rats

Objective To study the effects of sodium para-aminosalicylic acid on learning and memory and hippocampal ultramicro-structure of Sub-acute- manganese-exposed rats. Materials and Methods 48 SPF healthy male Sprague–Dawley rats (weight 180±20g) were randomly divided into normal control group, manganese-exposed group, PAS-Na low(L-PAS) and high(H-PAS) dose treatment group ,and 12 in each group. Mn infected rats (Mn-exposed group, L-PAS and H-PAS group )received daily intraperitoneally (i.p.) injections of 15 mg MnCl2·4H2O /kg as the capacity of the control group normal saline ip, 5 days / week for three weeks. L-PAS and H-PAS group rats were followed by a daily subcutaneously (s.c.) dose of PAS-Na 100 and 200 mg/kg respectively for another 5 weeks,as the capacity of the back subcutaneous injection of normal saline of the remaining rats, The ablility of learning and memory was tested by Morris Water Maze(MWM) and the alterations of ultramicro-structure in hippocampal granular layer of rats were observed by transmission electron microscope.After the rats sacrificed,organs were weighted and determination of serum SOD, GSH-Px activity, MDA was complished ,with Mn, Fe, Zn, Cu, Ca, Al, Mg content of blood, liver, kidney, spleen, testes, femur, iliac bone, cortex and hippocampus,and transmission electron microscopy observation of the ultrastructure changes of rat hippocampal CA1 area. Results Manganese in blood, liver, cortex, femur, bone,and testis ,and iron in blood and liver , and magnesium in blood and spleen, and zinc in liver of Mn-exposed group rats were significantly increased,while iron in cortex, and copper in kidney, cortex and iliac,and zinc, calcium and magnesium in blood, kidney and cortex, and magnesium in femur were significantly decreased. Manganese in cerebral cortex and iliac,and zinc in liver,and calcium in femur,and magnesium content in blood and spleen were significantly lower after PAS-Na treatment,while iron, magnesium, copper in cortex and copper in kidney were significantly higher. Content of serum MDA of Mn infected rats was significantly increased,followed by obvious decreasing after PAS-Na treatment. The score of escape latency, swimming distance and the wear ring of Mn-exposed group was lower than the nomral control group,but lower than the PAS-Na treatment groups(L-PAS and H-PAS group),with no significant difference. Neurons degeneration, apoptosis and oncosis, translucent swelling of neuronal processes, quality of structure axis disorders, nerve-tubulin and neurofilament distortion, interruption, mitochondrial swelling, and blurred, broken and vacuolizated cristae after the collapse were observed in the Mn-exposed group rats,suggesting that mitochondria is susceptible to manganese toxicity of cell damage.The oncosis hippocampal neurons were not typical and mitochondrial structure restorated near to normal after PAS-Na treatment , particularly common in the H-PAS group.Conclusion PAS-Na treatment can effectively remove Manganese from the cerebral cortex and iliac,and reduce the content of serum MDA,and mitochondrial structure restorated near to normal, especially obvious in H-PAS group,suggesting that PAS-Na may interfere the manganese toxicity in hippocampal neurons.