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Abstract Summary Diabetes mellitus is considered one of the most prevalence diseases. The nephropathy, retinopathy and neuropathy complications accompanied to this disease are resulting from hyperglycemia and increased free radicals. So the treatment using anti-free radicals and antioxidants play an important role in controlling these complications. So the current study aimed to determine the effect of Egyptian white and black mulberry fruits and leaves extracts which contain DNJ as anti-free radical substance on controlling the biological and biochemical changes in diabetic nephropathy induced in adult male rats. This study was divided into 3 parts: The first part included the extraction of DNJ from white and black mulberry fruits and leaves by different solvents (water- methanol- ethanol) and the determination of DNJ content in these extracts by HPLC to determine the best solvent for extraction. The results showed that water is the best solvent and that black mulberry leaves contain the highest amount of DNJ about 313.6 mg% while white mulberry leaves contain about 137.7 mg%. Mulberry fruits contain less amount of DNJ as compared with leaves where white fruits contain 70.8 mg% and black fruits contain 32.6 mg%. Summary 134 The second part of the study depended upon the determination of anti-free radical activity of water extracts of mulberry. Results showed that different water extracts containing DNJ have scavenging hydroxyl radical effect ranging from 11.6 to 41.4 % employed from concentrations ranging from 1.25 to 100 µg /ml, respectively. The third part of this study is the biological experiment: 72 healthy adult male albino rats SpragueDawley strain with mean weight range 217-220 g fed on balanced diet till the end of the experiment. 12 healthy rats were injected subcutaneously with citrate buffer and used as healthy control group (group 1) received tap water. Other rats were injected subcutaneously by STZ (40 mg/ kg body weight) to induce diabetes. Diabetic status was confirmed after three days of injection by measuring blood glucose level. Rats with blood glucose level more than 200 mg/dl is considered diabetic and were divided into 5 groups (12 each): group (2) diabetic control received tap water ; group (3) diabetic treated with WMFWE; group (4) diabetic treated with WMLWE; group (5) diabetic treated with BMFWE and group (6) diabetic treated with BMLWE. All the extracts used in this experiment were given at a daily dose contain 50 mg DNJ / kg body weight by gavage tube for 28 day. Summary 135 The experiment confirmed the following results: 1) The injection with STZ caused significant increase in food intake and decrease in body weight and feed efficiency ratio by about 43.03, 292.13 and 225 %, respectively as compared with healthy control group. While the relative kidneys weight was increased in diabetic group by about 84.0% as compared with the healthy control group. Treatment of diabetic rats from group (3) to group (6) with the different mulberry water extracts led to decrease in food intake by 11.46, 0.61, 14.28 and 16.11 %; and increase in body weight change by about 52.39, 36.87, 57.17 and 32.77%, improve feed efficiency ratio 50.0, 40.0, 50.0 and 20.0 %; and decrease in relative kidneys weight by 13.04, 4.35, 30.43 and 2.17%, respectively. 2) The results showed that injection with STZ led to significant increase in blood sugar level and decrease in insulin level by 244.58 and 39.23 %, respectively as compared with healthy control group. Also the results showed that treatment with the four tested extracts decrease blood sugar level and increase insulin secretion in group (3) to group (6) by 44.52, 49.52, 55.92 and 56.18% for glucose and 28.54, 29.80, 24.96 and 36.61% for insulin respectively as compared with the diabetic group. Summary 136 3) The induction of diabetes in rats caused significant increase in blood glycated hemoglobin percentage and renal aldose reductase activity as a result for complications of diabetes. On the other hand the treatment of group (3) to group (6) with the tested extracts controlled the increment in glycated hemoglobin as compared with diabetic control group by 65.46, 66.48, 64.57 and 66.89%, respectively and caused decrease in aldose reductase activity as compared with diabetic control group by 36.28, 45.22, 29.50 and 48.78 %, respectively. Also renal total protein was affected by STZ injection and improved in groups treatment with the different extracts by 50.11, 77.38, 48.72 and 67.83%, respectively as compared with diabetic group. 4) Consumption of the tested extracts caused significant improvement in oxidative stress status as compared with the diabetic group in which there was significant increase in renal NO, MDA and AOPPs levels and significant decrease in renal GSH content by 459.57, 40.29, 223.58 and 26.99 %, respectively as compared with the healthy control group. The improvement in treated groups from group (3) to group (6) as compared with diabetic control group were: Summary 137 a) Decrease renal NO level by 64.52, 66.72, 49.03 and 69.51 %, respectively. b) Decrease renal MDA level by 25.49, 25.50, 27.65 and 27.65 %, respectively. c) Decrease renal AOPPs level by 55.95, 67.50, 55.75 and 63.66 %, respectively. d) Increase renal GSH content by 15.99, 16.59, 11.16 and 6.66 %, respectively. 5) It was clear from the results of serum creatinine, urea, uric acid and total protein that kidney functions is effected in diabetic rats due to kidney complications. Treatment of diabetic rats with the tested extracts for 28 day led to improvement in kidney functions as following for group (3) – (6) as compared with diabetic control group : a) Decrease serum creatinine level by 21.00, 62.43, 51.47 and 62.72 %. b) Decrease serum urea level by 38.56, 41.52, 37.99 and 44.59 %. c) Decrease serum uric acid level by 38.44, 39.13, 36.90 and 47. 63 %. d) Increase serum total protein level by 24.61, 26.72, 13.36 and 23.85 %. In general results showed that oral daily consumption of water extracts of white and black mulberry fruits and leaves improve diabetic status and control diabetic complications. |