Dissertation
Dissertation > Medicine, health > Preventive Medicine,Health > Health - basic science > Health Toxicology

Intervention of Melatonin for Acrylamide-induced General Toxicity and Neurotoxicity in Rats

Author ZengLiAi
Tutor YanHong
School Huazhong University of Science and Technology
Course Health Toxicology
Keywords Acrylamide Melatonin General Toxicity Neurotoxicity Gait Scores Neuropathic Injury Oxidative Damage
CLC R114
Type Master's thesis
Year 2011
Downloads 33
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Acrylamide(ACR) is an important industrial chemical primarily.Since the first synthesis in 1949, it has been used extensively in the production of polyacrylamide and other hundreds of products. In scientific laboratories, ACR are often applied for the electrophoretic separation of proteins. In daily life, the ways people access to acrylamide are various. In recent years, it is found that, besides occupational sources of exposure, people can expose to it by smokeing, cosmetics, food packaging materials, and even through food such as drinking water, fried potato chips, french fries, bread so forth and so on. The harmful effect of ACR has attracted the public much attention. After decades of research, regarding to the toxicity of acrylamide human benings have a full understanding. It is a cumulative poison, with apparent neurotoxicity, male reproductive toxicity and suspected carcinogenic, but only neurotoxicity was confirmed in humans.While the exact mechanism for neurotoxicity has not been completely clear until now. It was suggested that oxidative damage be one of the causes of neurotoxicity induced by ACR, and some antioxidants such as vitamin C and vitamin E could reduce the symptoms.Melatonin (MT) is a pineal hormone. Recently, studies have revealed that MT have a broad spectrum of physiological and pharmacological capability, it could regulate the anti-aging, tumor growth and prevent certain neurodegenerative diseases. It is also well known that MT is the strongest antioxidant, it could clear away free radical and improve the antioxidant enzymes activity by direct or indirect way.In this reseach, the intereference effect of MT against ACR-induced general and neuro toxicity in rats was studied. Moreover, the possible mechanism of ACR–induced neurotoxicity was also studied.PartⅠStudy of MT Interference against the General Toxicity Induced by ACR in RatsObjective: To study the effect of MT ,when exposed at the same time,on general toxicity induced by ACR in rats.Methods: 40 adult male SD rats were randomly divided into four groups,10 in each group.Rats were housed individually in polycarbonate boxes. The control group was treated with sterile water by oral ingestion; ACR group was administered by oral ingestion at 2.3 mmol/L ACR in drinking water; MT group was administered by i.p.injection at 2.5㎎/ kg MT and treated with sterile water by oral ingestion; Joint group(MT + ACR group) was administered by oral ingestion at 2.3 mmol/L ACR in drinking water,and administered by i.p.injection at 2.5㎎/kg MT per day .All the groups were associated with long-term for 9 weeks. Food intake,water consumption and body weight were calculated once a week. The serum biochemical indicators were determined after experiment. The absolute and relative organ weights of cerebrum, cerebellum, heart, liver, spleen, kidney, testis were also examed.Results:(1)Compared with control group, food utilization efficiency slowed down apparently (P<0.05). Body weight gain in ACR group and joint group was suppressed (P<0.05).The relative organ weights of cerebrum and cerebellum increased significantly(P<0.05). The blood ALB and Cr decreased markedly(P<0.05). (2)Compared with control group, body weight gain in MT group was suppressed significantly at week 7 and week 8 ,and the blood ALB, TP reduced(P <0.05 ). (3) Compared with ACR group, the body weight of rats in joint group dropped at week 8 and the relative organ weights of cerebrum rised (P<0.05).Conclusion: ACR could slowe down food utilization efficiency, inhibit the growth of rats and increase the relative organ weights of cerebrum and cerebellum. MT failed to change the phenomenon when interfered at the same time.PartⅡStudy of MT Interference against the Neurotoxicity Induced by ACR in Rats1 MT Interference in the ACR-induced Neurobehavioral Abnormality Objective: To study the effect of MT, when administered simultaneously, on gait abnormalites induced by ACR in rats.Methods: 40 adult male SD rats were randomly divided into four groups,10 in each group.Rats were housed individually in polycarbonate boxes. The control group was treated with sterile water by oral ingestion; ACR group was administered by oral ingestion at 2.3 mmol/L ACR in drinking water; MT group was administered by i.p.injection at 2.5㎎/ kg MT and treated with sterile water by oral ingestion; Joint group(MT + ACR group) was administered by oral ingestion at 2.3 mmol/L ACR in drinking water,and administered by i.p.injection at 2.5㎎/kg MT per day .All the groups were associated with long-term for 9 weeks. Gait scores were analyzed separately once a week.Results: (1)The rats exhibit gait abnormalities in ACR group and joint group from week 3 to the end of experiment. Compared with control group,gait scores rised markedly(P<0.05). (2) Compared with ACR group, gait scores in joint group decreased snificantly at week 4 and week5(P<0.05). Conclusion:ACR could make the rats exhibit gait abnormalities in this model. MT could alleviate the gait abnormalities induced by ACR at the early stage but failed to show any protective effects later.2 MT Interference in the ACR-induced Neuro Histopathological InjuryObjective: To explore the effect of MT,when treated at the same time,on neuro histopathological injury induced by ACR in rats.Methods: 12 adult male SD rats were randomly divided into four groups,3 in each group.Rats were housed individually in polycarbonate boxes. The control group was treated with sterile water by oral ingestion; ACR group was administered by oral ingestion at 2.3 mmol/L ACR in drinking water; MT group was administered by i.p.injection at 2.5㎎/ kg MT and treated with sterile water by oral ingestion; Joint group(MT + ACR group) was administered by oral ingestion at 2.3 mmol/L ACR in drinking water,and administered by i.p.injection at 2.5㎎/kg MT per day .After experiment, the histopathologial injury of cerebrum, cerebellum, sciatic nerve was obversed by HE stain.Results: (1) In control group,the layers of cell in cerebrum was clear, while in ACR group the vascular was expansion and hyperemia, and there were inflammatory cells infiltrating. MT group and joint group did not appear apparently unusual compared with control group. (2) In control group, there were obvious three-layer structure: molecular layer, purkinje cell layer and granular cell layer in cerebellum, and the other three groups have no obvious abnormity. (3) In control group,the myelinated fibers distributed homogeneously in sciatic nerve, and the other three groups show no obvious change.Conclusion: ACR could lead to vascular expansion and hyperemia, inflammatory cells infiltrating in cerebrum. MT could alleviate the situation. 3 MT Interference in the ACR-induced Oxidative DamageObjective: To study the effect of MT ,when interfered at the same time,on oxidative damage induced by ACR in rats.Methods: 40 adult male SD rats were randomly divided into four groups,10 in each group.Rats were housed individually in polycarbonate boxes. The control group was treated with sterile water by oral ingestion; ACR group was administered by oral ingestion at 2.3 mmol/L ACR in drinking water; MT group was administered by i.p.injection at 2.5㎎/ kg MT and treated with sterile water by oral ingestion; Joint group(MT + ACR group) was administered by oral ingestion at 2.3 mmol/L ACR in drinking water,and administered by i.p.injection at 2.5㎎ /kg MT per day .At the end of experiment,the content of Malondialdehyde(MDA) and reduced Glutathione (GSH) ,the activity of Superoxide dismutase(SOD) and Glutathione peroxidase(GSH-Px) in cerebral cortex and cerebellum tissue were determined.Results: In this model, (1) Compared with control group,the activities of SOD remarkably decreased in ACR group in cerebral cortex (P<0.05), while the content of MDA and GSH ,the activity of GSH-Px did not appear apparently change. The activities of SOD remarkably increased in MT group in cerebral cortex (P<0.05) . Compared with ACR group, the activities of SOD significantly rised in joint group in cerebral cortex (P<0.01). (2) Compared with control group,the activities of SOD and the content of GSH remarkably dropped in ACR group in cerebellum (P<0.05), while the content of MDA and the activity of GSH-Px did not show obvious unusual. Compared with ACR group, the content of MDA and GSH, the activity of SOD and GSH-Px did not show apparently abnormality in joint group in cerebellum(P>0.05).Conclusion:ACR could inhibit the activities of SOD in cerebral cortex and cerebellum,and also reduce the content of GSH in cerebellum.While MT could enhance the level of SOD and GSH when treated simultaneously. The above results show: in this animal model, ACR could suppress the growth of rats, increase the relative organ weights of cerebrum and cerebellum, make the rats exhibit gait abnormalities, lead to vascular expansion and hyperemia, inflammatory cells infiltrating in cerebrum, inhibit the activities of SOD in cerebral cortex and cerebellum,and also reduce the content of GSH in cerebellum. While MT could alleviate the gait abnormalities induced by ACR at the early stage but failed to show any protective effects later. MT could enhance the level of SOD and GSH when treated at the same time.

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