Effect of estrogen and N-acetyl cystein on bone remodeling and bone cytokine osteoprotegrin in ovarectomized rats

Osteoporosis is one of the most common metabolic bone diseases which is characterized by loss of bone mass and predominantly affects menopausal women due to the loss of estrogen. Although the link between estrogen deficiency and bone loss is well established, the mechanisms through which estrogen deficiency stimulates bone resorption and impairs bone formation remain controversial. Estrogen deficiency may lead to osteoporosis by decreasing the production of osteoprotegrin [OPG], one of the important local regulators of bone turnover or by down regulating antioxidant pathways. We investigated the impact of estrogen deficiency [induced by ovariectomy] on bone cytokine osteoprotegerin and the process of bone remodeling. Also, we compared between the effect of estrogen replacement therapy and thiol antioxidant [NAC] supplementation in the protection against bone loss produced by estrogen deficiency. This study was carried out on fourty female Wistar rats, and divided into two main groups: normal control rats [n=10] and ovariectomized rats [n=30]. The control group was sham operated and received a weekly subcutaneous injection of a vehicle [100 micro L sesame oil]. The ovarectomized group was subjected to ovariectomy and was further subdivided into 3 subgroups; a non-treated group, 17-beta estradiol injected group and N- acetyl cystein [NAC] injected group. At the end of the experimental period, blood samples were collected from all experimental rats for measuring: serum alkaline phosphatase, serum osteocalcin and serum estradiol. Urine samples were also collected for measuring: urine hydroxyproline and urinary calcium excretion. After the rats were sacrificed, one femur from each rat was weighted and homogenized for the estimation of OPG content. In ovariectomized group there was a significant decrease in the serum estradiol level and a significant increase in markers of bone resorption [urinary hydroxyproline and urinary calcium excretion] with a significant but insufficient increase in the markers of bone formation [serum alkaline phosphatase as well as serum osteocalcin] which cause a state of negative remodeling balance. Moreover, there was a significant decrease in bone OPG level as compared to the normal control group. All these effects were reversed in the 17-beta estradiol treated ovariectomized group. In addition, the markers of bone resorption and formation, as well as the OPG level were corrected after administration of NAC in ovariectomized rats. Estrogen deficiency can lead to osteoporosis through reduction of OPG level and increasing in the reactive oxygen species [ROS]. 17-beta estradiol administration leads to increased concentrations of OPG, which inhibits osteoclastogenesis. Also administration of NAC prevents the occurrence of high bone turnover in ovariectomized rats. This effect was suggested to be due to either increase the levels of SOD and GPx which are known to be decreased in ovariectomized rats or through the increased level of OPG by unknown signaling mechanism. Thus it is suggested that NAC can be used in the prevention and treatment of osteoporosis in postmenopausal women either alone or in combination with small doses of estrogen

effect of food deprivation and refeeding on some renal functions and renal NA+-K+ ATPase activity in rats

Starvation is considered as a safety manner for reduction of weight in obesity taking into consideration the time factor and the ample supply of water. Results of the study proved that the metabolic responses and the changes in renal functions during starvation are reversible. This work was conducted on 28 rats divided into four groups, one control group and three fasted groups for three days with free access to water, two of the fasted groups were refed for two and five days. The body weight, the water intake and urinary output were decreased during starvation then normalized after refeeding. Significant decrease in creatinine clearance, urea excretion, blood bicarbonate and blood pH were observed during starvation, then returned to normal at the end of the fifth day of refeeding. Significant increase in serum sodium was reported while serum potassium was not affected; urinary excretion of sodium and potassium were decreased but all normalized on refeeding. Starvation did not alter serum chloride. Renal Na+ - K+ ATPase activity was significantly increased during starvation and normalized on refeeding

Hyperpafathyroldlsm in cases of induced acute diabetes mellltus in rats

This study was conducted on twenty male rats [ten Tats used as a control group and ten became acutely diabetic after intraperitoneal injection with streptozotocin]. Diabetes was well established by the third day. Radioimmunoassay for parathormone in serum revealed significant hyperparathyroidism Significant reduction in total serum calcium while serum phosphorous was significantly increased. In urine there was significant hypercalciuria, significant hyperphosphaturia, and significant increase urinary magnesium

Chronic diabetes mellitus: osteotic and mineral changes in human beings and rats

Clinical examination and Laboratory investigations done to IS male type I chronic diabetic patients [insulin dependent more than 5 years] and to an age mached group of 10 normal male volunteers revealed normocalcaemia and normomagnesaemia with significant hyperphosphataemia. Estimation of serum level of parathormone showed significant hypoparathyroidism. An addition, significant hypercalcuria, hyperphosphaturia and hpermagnes uria were also detected. Histopathological examination of trabecular bone biopsies from both groups revealed marked osteoportic changes among the diabetic patients. Biochemical analysis of similar bone samples supported the microscopic findings by demonstrating significant decrease of calcium contents of the bone in the diabetic group. In the chronic rats [7 weeks after streptozotecin induction] significant hypercalcaemia, hyperphosphataemia and normomagnesaemia were found. Their sera showed significant hypoparathyroidism. In addition, significant hypermagnesuria. Histopathological examination of the rat's right tibiae revealed advanced rachitic changes. Biochemical analysis of the left tibias approved the microscopic findings by showing significant decrease in bone calcium contents

T-cell immune function in psoriatic patients as regards release of Interleukin-2

Levels of interleukin-2 were estimated [using the radioimmunoassay technique] in sera of patients suffering from chronic plaque type psoriasis vulgaris with moderate disease activity and without arthropathy. All patients were receiving non-steroidal topical treatment. Ten healthy volunteers were used as the control group. Our results showed non-significant changes as compared with the control group. These data showed that there is no systemic alteration of intreleukin-2 our psoriatic patients