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العنوان
Effect of Melatonin on High Salt-Induced Metabolic Changes in Ovariectomized Rats /
المؤلف
Khashab, Howida Ahmed El-sayed Saleh.
هيئة الاعداد
باحث / هويدا أحمد السيد صالح خشب
مشرف / منى أحمد أحمد
مشرف / داليا عبد السلام سعد
مشرف / دعاء أحمد أبو بكر
تاريخ النشر
2020.
عدد الصفحات
317 P. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
علم وظائف الأعضاء (الطبية)
تاريخ الإجازة
1/1/2020
مكان الإجازة
جامعة عين شمس - كلية الطب - قسم الفسيولوجيا الطبية
الفهرس
Only 14 pages are availabe for public view

from 317

from 317

Abstract

The present study was planned to determine the possible modulatory influence of melatonin supplementation on disturbed glucose and lipid homeostasis in ovariectomized rats subjected to high salt loading. The study was carried out on 50 adult female albino Wister rats initially weighing 200-250 g.
Rats were randomly allocated into the following 4 groups:
1. Sham-operated control group (n=12)
Rats were subjected to sham operation for ovariectomy and received tap water as drinking water together with i.p injection of melatonin solvent (1ml/kg, 6days/week).
2. Ovariectomized group (n=12).
Rats were subjected to bilateral ovariectomy and received tap water as drinking water together with i.p injection of melatonin solvent (1ml/kg, 6days/week).
3. High salt ovariectomized group (n=12).
Rats were subjected to bilateral ovariectomy and received high salt (2% NaCl) as drinking water together with i.p injection of melatonin solvent (1ml/kg, 6days/week).
4. Melatonin-treated high salt ovariectomized group (n= 14). Rats were subjected to bilateral ovariectomy and
 Summary and Conclusion
203
received high salt as drinking water together with i.p injection of melatonin (10mg/kg, 6days/week).
Rats were studied after the end of the experimental period which lasted for 8 weeks. All rats were subjected to determination of:
-Body weight (BW), body mass index (BMI) and waist circumference (WC), (all at start and end of experiment)
-Weights of visceral fat, pancreas and liver.
-Glucose uptake by diaphragm.
-Glucose output by both kidneys.
-Plasma levels of glucose, lipid profile and catalase.
-Serum levels of estradiol, insulin, malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α).
-Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
-Pancreas and liver histopathology.
-Caspase-3 in pancreatic tissue by immunohistochemistry.
Successful ovariectomy induction was assured by significant decrease in serum estradiol in all studied ovariectomized groups compared to sham-operated control group.
The results revealed that ovariectomized group displayed significant increase in final BW and its % change, final BMI and
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204
final WC and its % change. Also, there was significant increase in levels of plasma glucose, serum insulin and HOMA-IR and significant decrease in glucose uptake by diaphragm. Plasma levels of TG, TC and LDL-C and AI were significantly increased, whereas plasma HDL-C was significantly decreased. This was associated with significant increase in serum MDA and TNF-α and plasma catalase.
High salt ovariectomized group exhibited significant decrease in final WC and its % change together with significant increase in HOMA-IR and serum levels of insulin, MDA and TNF-α, compared to ovariectomized group. Plasma levels of glucose, TG, TC and LDL-C and AI and plasma catalase were significantly increased and plasma HDL-C was significantly decreased compared to sham-operated control group.
Melatonin supplementation resulted in significant decrease in VFW and VFW/FBW, plasma glucose, serum insulin and HOMA-IR. The lipid profile revealed significant decrease in plasma levels of TG, TC and LDL-C and AI together with significant increase in plasma HDL-C. Also, levels of serum estradiol and plasma catalase were elevated, whereas serum levels of MDA and TNF-α were significantly reduced.
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Histological examination of pancreas of ovariectomized group revealed few numbers of islets of Langerhans with attenuated or absent cells in the center. In high salt ovariectomized group, some of pancreatic lobules showed increased number of islets of Langerhans and others showed fatty degeneration. Melatonin treatment restored normal pancreatic morphology, in which islets appeared with normal number and cellularity resembling control group.
The apoptotic marker, caspase-3 in pancreas islets was found to be significantly increased in ovariectomized group, more prominent in high salt ovariectomized group, being significantly increased compared to both ovariectomized and control groups. In melatonin-treated group, caspase-3 was mild, being significantly decreased compared to both high salt ovariectomized and ovariectomized groups and comparable to control group.
Histological examination of liver of ovariectomized group revealed irregular organization of hepatocyte cords with dilated blood sinusoids and increased collagen fibers around portal tract. High salt ovariectomized group showed a worsened hepatic morphology, in form of hepatocyte vacuolation, ballooning, steatosis and inflammatory infiltration together with massive amount of collagen fibers around portal tract. This picture was suppressed by melatonin supplementation which almost restored normal hepatic architecture.
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from the aforementioned results, it could be concluded that ovariectomy, which represents a model of estrogen depletion that mimics the postmenopausal women, is associated with detrimental metabolic profile manifested as weight gain, obesity, hyperglycemia, insulin resistance and hyperlipidemia. These ovariectomy-promoted deleterious effects are most likely related to estrogen deprivation together with augmentation of oxidative and inflammatory states.
High salt intake in combination with ovariectomy exacerbated the hyperinsulinemia and insulin resistance and intensified pancreatic apoptosis and hepatic fatty and degenerative changes, effects that could be explained by salt loading-induced acceleration and exaggeration of the oxidative and inflammatory insults.
Melatonin supplementation improved the metabolic derangement induced by salt loading and ovariectomy as evidenced by the anti-adipogenic effect, amelioration of hyperglycemia and insulin resistance, enhancing insulin sensitivity and anti-atherogenic lipid profile. These favorable influences of melatonin could be mediated via a direct effect, elevation of estradiol level as well as its antioxidant, anti-inflammatory, anti-apoptotic and anti -
steatotic effects. Therefore, this useful metabolic impact of melatonin highlights its potential role as an effective agent against
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207
the metabolic deterioration that exists in conditions of high salt and estrogen deprivation.