This study was conducted in order to evaluate the effect of sericin-calcium (SC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after ovariectomy (OVX), Sprague-Dawley rats were divided randomly into three groups: sham-operated group (Sham), ovariectomized group, and SC-treatment group (OVX+SC). Rats in the OVX+SC group were given drinking water containing 0.07% SC for eight weeks. Bone breaking force, mineralization, and blood parameters related to bone metabolism were analyzed. In OVX animals, blood concentration of 17β-estradiol showed a significant decrease, while osteocalcin and type I collagen C-terminal telopeptides (CTx) showed an increase. Breaking force of femurs as well as bone mineral density (BMD), ash, calcium, and phosphorus in femurs showed a significant decrease following OVX. Treatment with SC (0.07% in drinking water) resulted not only in remarkable restoration of the decreased 17β-estradiol and increased osteocalcin and CTx concentrations, but also led to recovery of decreased femoral breaking force, BMD, ash, calcium, and phosphorus. It is suggested that SC effectively improves bone density by preventing bone turnover-mediated osteocalcin, CTx, and minerals, and that it could be a potential candidate for use in therapy or prevention of post-menopausal osteoporosis.
The effects of isotonic saline on corneal penetration, thickness, and injury, as well as lacrimal secretion in a rat model of dry eye were investigated, in comparison with distilled water. Male Sprague-Dawley rats received intraperitoneal administration of atropine sulfate (20 mg/kg) and their eyes were exposed to dry (relative humidity 25-35%) air flow (2.4 m/sec), under Zoletil anesthesia, for 5 hr to induce dry eye. During the period of dry eye induction, distilled water or isotonic saline (5 μl) was instillated onto the cornea every 30 min. Corneal penetration was measured through fluorescein dye quantification, and corneal thickness and injury were examined under a microscope. Lacrimal (tear) secretion and mucin-like glyocoprotein excretion from goblet cells were measured using the Schirmer test and microscopy, respectively. In dry eye rats treated with distilled water, corneal thickness, tear secretion, and mucin-like glycoprotein excretion were decreased to 74.0%, 74.1%, and 46.3% of normal levels, respectively, resulting in marked corneal injury and a significant increase in corneal penetration. In comparison, treatment with isotonic saline resulted in recovery of lacrimal secretion, in spite of a slight improvement of mucin-like glycoprotein excretion, and thereby prevented corneal penetration of fluorescein by 10%. The results indicate that repeated instillation of isotonic saline could provide slightly greater protection from corneal injury, compared with distilled water by facilitating lacrimal secretion, in addition to relief of inconvenience and pain.
This study was conducted in order to investigate repeated-dose toxicities of Magnolia ovobata ethanol extract (MEE). MEE was administered orally to male and female Sprague Dawley rats at dose levels of 0, 500, 1,000, or 2,000 mg/kg for four weeks. Repeated administration of MEE did not induce abnormalities in general signs, body weight gain, feed and water consumption, necropsy findings, or organ weights. In addition, no abnormality was observed in hematological analyses; red blood cells and their indices, white blood cells, platelets, and coagulation times. In male rats, BUN and creatinine showed an increase at doses of 2,000 mg/kg and 500-1,000 mg/kg, respectively, while in female rats, lactate dehydrogenase and creatine phosphokinase showed a decrease at 2,000 mg/kg, the upper-limit dose of repeated-dose toxicity studies. However, there were no dose-dependent increases or gender-relationship. In addition, other parameters of the hepatic and muscular toxicities as well as energy and lipid metabolism were not affected. In microscopic examination, no considerable pathological findings were observed. The results indicate the safety of oral administration of MEE to the upper-limit dose.
The present study was carried out to establish an animal model, displaying long-term learning and memory dysfunction, since single intracerebroventricular (icv) injection of amyloid β peptide (Aβ) causes a short-term memory impairment. Male ICR mice were fed a high-cholesterol diet (HCD) containing 3% cholesterol, 1% corn oil and 0.5% cholic acid, and 1 week later, icv injected with Aβ1-42 (5 μg/head). Learning/ memory function was assessed via passive avoidance performances 1 day and 2, 4, and 6 weeks after Aβ1-42 injection, in addition to blood biochemical analyses for lipid profiles and hepatic function. Total cholesterol, lowdensity lipoproteins and hepatic dysfunction parameters markedly increased, while high-density lipoproteins were reduced following HCD feeding. Whereas single injection of Aβ induced temporary memory loss 1 day after administration, exhibiting full recovery after 2 weeks, Aβ treatment in combination with HCD feeding lasted the learning/memory impairment up to 6 weeks. Therefore, it is suggested that hypercholesterolemia augments Aβ-induced memory loss, and that Aβ injection plus HCD feeding could be a long-term memorydeficit model suitable for long-term treatment with drugs or stem cells.
Four-week repeated-dose toxicity of Misaengtang (MST) was evaluated according to Toxicity Test Guideline of Korea Food and Drug Administration using 6-week-old Sprague-Dawley rats. Based on the results of preliminary single-dose toxicity study, confirming safety up to an upper-limit dose, MST was dissolved in drinking water and orally administered at doses of 500, 1,000, or 2,000 mg/kg for 28 days. All doses including the upper-limit limited dose (2,000 mg/kg) of MST did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology and blood biochemistry. Rather, high doses (1,000-2,000 mg/kg) of MST reduced the serum levels of alanine transaminase, aspartate transaminase, creatinine phosphokinase, lactate dehydrogenase and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Both maximum-tolerable dose and no-observed-adverse-effect level were not determined. The results indicate that long-term intake of high-dose MST might not induce general adverse-effects.