الفهرس 
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Abstract
Diabetes mellitus is a metabolic disorder in which the effectiveness of insulin /or the delivery of insulin to the tissues are reduced. It characterized by hyperglycemia usually accompanied by glucosuria. chronic abnormality of glucose tolerance is an associated with long term damage and failure of various organ systems; mainly affecting the eyes, nerves, kidneys and the heart. Diabetes mellitus and cigarette smoking are major public health burdens. Both are strong risk factors for cardiovascular diseases (CDVs) and their co-occurrence have dramatic impact on the absolute risks challenged human health lead to increase the risk of mortality. COS is an amino polysaccharide derived from chitin which present in the exoskeleton of crustacean. It acts as antimicrobial, antioxidant, antifungal, antidiabetic, anti-obesity, anti-cancer, anti-inflammatory and anti-allergic agent due to its chemical and biological properties. The aim of this study was to investigate the impact of COS administration in case of nicotine toxicity in adult healthy and corresponding diabetic male rats.
Throughout the present study, Eighty adult male Sprague-Dawely rats weighing 190±10g were divided into two sections: healthy and diabetic sections; diabetes induced by STZ at a single dose of 40mg/kg body weight given interpretionally after 12hours fasting followed by administration of 5% glucose solution, three days later serum glucose level reached 200±10 mg/dL. Each section divided into four groups each group contain 10 rats, control group1 healthy rats fed on the balanced diet, group2: orally administrated COS (given at dose of 500mg/kg body weight daily by gastric tube), group3: treated with nicotine (injected subcutaneously to rats at dose of 3mg/kg body weight daily)
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and group4: administrated both COS and nicotine (at the tested dose).
All animal weekly weighted and the eaten diet daily recorded. At the end of experiment (6 weeks), after 8 hours fasting blood sample from eyes were taken from all rats for fasting blood glucose determination. Then All rats were scarified under ether anesthesia after 12 hours fasting. Blood samples were collected, and organs were separated then kept in plastic vials at-20ºC until used for biochemical analysis.
1- from the results of the nutritional indices, diabetes induction showed a significant decrease in food intake, gain in body weight and FER, while it caused a significant increase in FCR as it affects the nutrient metabolism. Moreover, COS administration in healthy rats caused non-significant differences in food intake, it significantly decreased the gain in body weight and FER, and increased the FCR. COS have an ameliorative effect on the nutritional indices in diabetic groups either alone or with nicotine comparing with the diabetic control. While nicotine administration caused a significant decrease in food intake, gain in body weight, FER. and increased the FCR either in healthy or in diabetic groups.
2-Next we determined the levels of diabetic biomarkers, scince diabetes induction showed a strongly significant increase in serum glucose level by 239.23% and in HOMA-IR by 37.11% compared with the healthy control group. Diabetic control group showed a significant decrease in serum insulin by 59.60%, liver glycogen content by 45.28% and in liver glucokinase enzyme activity in liver tissue by 54.26% comparing with the healthy control group. COS administration to healthy rats caused non-significant differences in glucose level, serum insulin, HOMA-IR, liver glucokinase activity but
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it caused a slightly significant increase in the liver glycogen content in healthy rats, on the other hand, it caused a significant ameliorative effect on this diabetic biomarkers caused by diabetes alone or with nicotine. Nicotine administration either in healthy or diabetic groups worsened the diabetic biomarkers. It caused a significant increase in serum glucose level and HOMA-IR, decreased the insulin level, liver glycogen content and liver glucokinase enzyme activity.
3- For the results of lipids profile, diabetes induction showed a significantly incease the values of TAGs by 24.01%, TC by 51.95% ,VLDL-C by 24.02%,LDL-C by 172.11%, RF by 388.17% and AI by 42.94% comparing with the healthy control group. Where, COS administration showed non significant differences in healthy rats, However, its administration significantly dereased these values in the diabetic rats. COS administration significantly increased the values of HDL-C in both healthy and diabetic rats. In contrast nicotine adminisration showed a significantly incease the values of TAGs, TC,VLDL-C, LDL-C, RF and AI with decreased the HDL-C values in both healthy and diabetic rats.
4-The results of liver function confirmed that COS antioxidant activity inhanced the liver function as shown by significantly decreased the serum activities of ALT and AST in both healthy and diabetic groups. Also, nicotine administration caused an oxidative stress resulted in liver injury and significantly increased the serum ALT and AST enzyme activities in both healthy and diabetic groups.
5- Diabetes caused alteration in the kidney function, diabetes induction showed a strongly significant increase in serum urea by 112.02% , serum creatinine by 47.5% and urine albumin by 5.06% comparing with the healthy control. Also, it
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caused a slighty significant decrease in urine urea by 3.22% and urine creatinine by 40.29% comparing with the healthy control group. COS improved the renal function and protected it from the toxicity of nicotine and diabetes, it caused a significant decrease in serum urea, serum creatinine and urine albumin, in addition, it caused a significant increase in urine urea and urine creatinine. Where, nicotine worsened the kidney function tests in both healthy and diabetic rats compared with the healthy rats. It caused significant increase in serum creatinine, serum urea and urine albumin and caused a decrease in urine urea and urine creatinine.
6-from the results of oxidative markers (MDA) and antioxidant enzyme (SOD) activity, it was clear that diabetes mellitus caused an oxidative stress in pancreatic cells. Resulting in decreased the antioxidant enzyme activity of SOD and increased the lipid peroxidation and production of MDA. It caused significant decrease in SOD activity by 52.20% and increment in the MDA by 95.39% comparing with the healthy control group. COS administration caused significant increase in pancreatic SOD activity and decreased in the level of MDA. Nicotine administration induced oxidative stress increased the level of MDA and decreased the SOD activity in both healthy and diabetic groups.
7- Concerning to the molecular study of DNA abnormality of the kidney, diabetes induction caused a significantly increase in the DNA damage of kidney cell, this may because of hyperglycemia risk effects on the kidney glomerulus. COS has antioxidant role due to the free amino group that reduced oxidative stress and enhanced the endogenous antioxidant defense status. Nicotine administration increased the lipid deposition in the kidney contributes to cellular damage and to the progression of diabetic nephropathy. It caused significant
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increase in DNA fragmentation in both healthy and diabetic groups.
8- Collectively the study results established the remarkable antidiabetic effect of COS most likely by control enhanced glucose metabolism, regulate lipids profile, with liver and kideny functions in addition of improving the oxidative stress. Following the effect of nicotine in both healthy and diabetic groups confirmed its increased toxicity as cosidered by increasing the oxidative stress that enhanced the lipids peroxidation and worsened lipids profile that finally lead to decrease the insulin sensetivity and production of IR. Moreover, the combination of COS with nicotine was proven to be able to reduce nicotine toxic effect.
9-The study recommend that regularly consume chitosan supplements at a dose of (500 mg /meal) can nullify the risk of postprandial blood glucose increase in diabetic patient . In addition ciggeratte smoking should be avoided specially for diabetic patients to prevent excessive oxidative stress that increase lipids peroxidation then lead to insulin resistance and excessive diabetic risks.
Conclusion and
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