Effect of supraphysiological dose of Nandrolone Decanoate on the testis and testosterone concentration in mature and immature male rats: A time course study

Background: Most studies on anabolic-androgenic steroids abuse have been done in adult rats, but few data are available to immature. Objective: This study was conducted to assay the effect of Nandrolone Decanoate (ND) on the testis and testosterone concentration in male immature rats compare with mature ones in short and long time. Materials and Methods: 40 mature rats were divided into 4 groups: group A (short term) and group B (long-term) received 10 mg/kg/day ND interaperitoneally for 35 and 70 days, respectively. Group C (control) without any treatment, and group D (vehicle) received dimethyl sulfoxide (DMSO) solution in two periods 35 and 70 days. 40 immature rats were divided into 4 groups same as mature ones. After surgery body weight, testis size, histomorphometry of testis, and serum testosterone level were evaluated. Results: Our results showed that ND decreased the number of Leydig cells in group B (39.9 ±. 919), group A (43.4 ±. 120), and long term (40.6 ±. 299) immature rats, which could result in a reduction of testosterone concentration significantly in all experimental groups except short term mature group. Number of sertoli cells, testis size, and diameter of seminiferous tubules decreased in the long-term immature group. Eventually, the number of sperm was decreased in mature and immature groups, but a severe depletion of sperm was occurred in both mature and immature in long time in comparison to the control group (p< 0.05). Conclusion: This time course study showed that supraphysiological dose of ND may negatively affect the number of Leydig cells, sperm cell, and testosterone concentration of immature rats in the same matter of mature rats. However, the number of sertoli cell, testis size, and seminferous diameter were decreased only in the long immature rats.

A randomised controlled trial comparing weight adjusted dose versus fixed dose prophylactic phenylephrine infusion on maintaining systolic blood pressure during caesarean section under spinal anaesthesia.

Background: Spinal anaesthesia is the standard of care for elective caesarean delivery. It has advantages over general anaesthesia. However the sympathetic blockade induced by spinal anaesthesia results in an 80 percent incidence of hypotension without prophylactic management. Current evidence supports co-loading with intravenous fluids in conjunction with the use of vasopressors as the most effective way to prevent and treat the hypotension. Phenylephrine is the accepted vasopressor of choice in the parturient. A prophylactic phenylephrine infusion combined with a fluid co-load is proven to be an effective and safe method of maintaining maternal hemodynamic stability. While most published studies have assessed the effectiveness of a prophylactic phenylephrine fixed dose infusion, few studies have assessed the effect of a prophylactic phenylephrine weight adjusted dose infusion on maintaining maternal hemodynamic stability following spinal anesthesia for a cesarean delivery. Objective: To compare the incidence of hypotension between women undergoing elective caesarean section under spinal anaesthesia, receiving prophylactic phenylephrine infusion at a fixed dose of 37.5 micrograms per minute versus a weight adjusted dose of 0.5 micrograms per kilogram per minute. Methods: One hundred and eight patients scheduled for non-urgent caesarean section under spinal anaesthesia were randomized into 2 groups; control group and intervention group using a computer generated table of numbers. Control group; Received prophylactic phenylephrine fixed dose infusion at 37.5 micrograms per minute. Intervention group; Received prophylactic phenylephrine weight adjusted dose infusion at 0.5 micrograms per kilogram per minute Results: The two groups had similar baseline characteristics in terms of ; Age, sex, weight and height. There was a 35.2% incidence of hypotension in the fixed dose group and an 18.6% incidence of hypotension in the weight adjusted dose group. This difference was found to be of borderline statistical significance p-value 0.05, and the difference in the incidence rates between the two groups was found to be statistically significant p= 0.03. The difference in the incidence of reactive hypertension and bradycardia between the two groups was not statistically significant: p-value of 0.19 for reactive hypertension and p-value of 0.42 for the incidence of bradycardia. There was also no statistically significant difference in the use of phenylephrine boluses, use of atropine, intravenous fluid used and the number of times the infusion was stopped. Conclusion: Among this population, the incidence of hypotension was significantly less in the weight adjusted dose group than in the fixed dose group. There was no difference in the number of physician interventions required to keep the blood pressure within 20% of baseline, and no difference in the proportion of reactive hypertension or bradycardia between the two groups. Administering prophylactic phenylephrine infusion at a weight adjusted dose of 0.5 micrograms per kilogram per minute results in a lower incidence of hypotension compared to its administration at a fixed dose of 37.5 micrograms per minute.

High-Dose Oral Ibuprofen in Treatment of Patent Ductus Arteriosus in Full-Term Neonates

Background: Patent ductus arteriosus (PDA) is an important risk for heart failure due to left to right shunt in term neonates. Objectives: In this study, we evaluated the effect of high dose ibuprofen in closure of PDA in term neonates. Patients and Methods: We used double dose ibuprofen (20 mg/kg, 10 mg/kg, and 10 mg/kg) for 3 - 30 day old term neonates with PDA who were admitted in the neonatal wards of Shiraz University of Medical Sciences. The results of this study were compared to the data of the previous study in our center which used the low dose of ibuprofen (10 mg/kg, 5 mg/kg, and 5 mg/kg). Results: 29 full term neonates received high-dose ibuprofen, in 18 neonates, PDA was closed after 4 days (62.1% versus 43.3% for the standard dose and 4.7% for the control group in the previous study) (P = 0.001). The results showed no significant correlation between the closure rate and gestational age, postnatal age, sex, and weight. In the 4th day of treatment, size of the pulmonic end of ductus arteriosus decreased from 2.09 mm to 0.77 mm compared to 1.68 mm to 0.81 mm in the standard dose of oral ibuprofen and 2.1 mm to 1.4 mm in the control group (P = 0.046). Conclusions: This study indicated that high-dose oral ibuprofen was more effective in closing or decreasing the size of PDA.

Effect of recombinant human erythropoietin expressions of apoptosis genes in rats following traumatic brain injury

Purpose: To explore the effect of recombinant human erythropoietin (r-HuEPO) on apoptosis in rats after traumatic brain injury. Methods: A total of 48 traumatic brain-injured Sprague Dawley (SD) rats were obtained by improved Feeney’s traumatic brain injury model, and were randomly divided into four groups: normal salinetreated rats (control) and rats treated with r-HuEPO at doses of 1000 U/kg, 3000 U/kg and 5000 U/kg. Brain tissues were collected on the 7th day after trauma surgery. Apoptotic cells, and NF-kappa B (NFĸB)-, c-myc-, and Fas/Fasl-positive cells were identified in brain tissues by immunohistochemical assay. Results: After treatment with r-HuEPO (3000 and 5000 U/kg), expression of NF-κB and Fas/Fasl were significantly decreased (p < 0.05) compared to control rats, especially at the 5000 U/kg dose (p < 0.01). However, for c-myc, no significant difference was observed between r-HuEPO treatment and control groups (p > 0.05). Compared to the 1000 U/kg r-HuEPO group, Fas/Fasl expression levels were significantly lower in the 3000 and 5000 U/kg r-HuEPO groups (p < 0.05). Additionally, expression of NF-κB and Fasl in the 5000 U/kg r-HuEPO group was significantly lower than that in the 3000 U/kg r- HuEPO group (p < 0.05). Moreover, the number of apoptotic cells in the r-HuEPO group (5000 U/kg) was significantly lower than in the control group (p < 0.05). Conclusion: Thus, r-HuEPO may be beneficial for treating traumatic brain injury via inhibition of NFkappa B and Fas/Fasl expressions.

Protective effect of (-)-epigallocatechin gallate on ultraviolet b-induced skin damage in hairless mice

Purpose: To investigate the protective effect of green tea (-)-epigallocatechin gallate (EGCg) on ultraviolet B (UV-B)-induced skin damages in hairless mice in order to develop a natural sunscreen compound for use in skin care products and cosmetics. Methods: EGCg was dissolved in acetone at concentrations of 1.0, 10.0 and 50.0 mg/mL, and topically applied to the skin of hairless mice at doses of 0.2 mL/cm2, with acetone as control. The mice were then irradiatd m2 UV-B for 30 min daily. EGCg treatment and UV-B irradiation were carried out daily for 28 consecutive days. The mice were then sacrificed and their dorsal skin examined by transmission electron microscopy (TEM) on the 28th day. Results: UV-B irradiation induced severe macroscopic skin damage including chapping, cracking and abnormal desquamation in the treated hairless mice. EGCg showed dose-dependent protective effects against UV-B induced damage on the skin. Treatments with 10.0 and 50.0 mg/mL EGCg alleviated UVB-induced skin damage by suppressing both keratinocyte apoptosis and mitochondrial dysfunction, along with inhibiting the production of melanin pigment. Conclusion: Topical application of green tea EGCg shows dose-dependent protective effect against UV-B-induced damage on hairless mouse skin. Thus, the plant compound can potentially be used as an alternative agent for photoprotection against UV-B exposure.

Dose-dependent protection of reseveratrol against spinal cord ischemic-reperfusion injury in rats

Purpose: To examine the protective effects of resveratrol (RESV) against spinal cord ischemic reperfusion (SCIR) injury. Methods: Forty-eight male rats were divided into six groups: sham-operated (control-I), SCIR-treated (SCIR-II), rats receiving 20 mg/kg of RESV with SCIR (RESV 20+SCIR-III), rats receiving 40 mg/kg of RESV with SCIR (RESV 40+SCIR-IV), rats receiving 60 mg/kg of RESV with SCIR (RESV 60+SCIR-V), and rats receiving 50 mg/kg of methylprednisolone (MP) with SCIR (MP + SCIR-VI), for 7 days prior to IR (pre-treatment) and 7 days after IR (post-treatment). Results: The levels of oxidative markers (TBARS, MPO) and inflammatory markers (IL-1β, IL-6, TNF-α, and NF-p65) were concomitantly suppressed in RESV-treated rats, which showed improved locomotor function. A pronounced increase in the activities of antioxidant enzymes (SOD, CAT and GSH) was noted in the RESV group compared with the MP and SCIR groups. RESV and MP supplementation increased neuronal count with decreased nuclear degeneration. RESV (40 mg) exhibited greater protective effect than 20 mg and 60 mg of RESV and 50 mg of MP. Conclusion: The results show the neurotherapeutic potential of RESV (40 mg) to attenuate oxidative stress and the inflammatory response to SCIR injury.

Protective effect of Rhizoma drynariae extract on osteoporosis in ovariectomized rat model

Purpose: To investigate the therapeutic effect of Rhizoma drynariae extract (RDE) on ovariectomyinduced osteoporosis in rats. Methods: Female Sprague-Dawley rats were randomly assigned to a sham-operated group (control) and five ovariectomy (OVX) subgroups: OVX with vehicle (OVX), OVX with 17ß-estradiol (E2, 25 μg/kg/day), and OVX with RDE doses (40, 80, and 160 mg/kg/day). Daily oral administration of E2 or RDE started 4 weeks after OVX and lasted for 16 weeks. The bone mineral density (BMD) of the L4 vertebrae and right femurs was estimated. The length of each femur was measured with a micrometer gauge, and the center of the diaphysis determined. Three representatives L4 vertebrae were selected to evaluate the trabecular microarchitecture. Serum alkaline phosphatase (ALP), urinary calcium (U-Ca), urinary phosphorus (U-P), urinary creatinine (Cr) and osteocalcin (OC) levels were measured. Results: The study showed that high-dose of RDE significantly inhibited the bone mineral density (BMD) reduction of L4 vertebrae (0.20 ± 0.02 g/cm3, p < 0.05) and femurs (0.18 ± 0.02 g/cm3, p < 0.05) caused by OVX and prevented the deterioration of trabecular microarchitecture (p < 0.05), which were accompanied by a significant decrease in skeletal remodeling (p < 0.05) as evidenced by the lower levels of bone turnover markers. High-dose of RDE improved morphometric parameters, namely, Tb-N (3.8 ± 0.2 mm, p < 0.05), Tb-Th (0.083 ± 0.011 mm, p < 0.05) and Tb-Sp (0.19 ± 0.01 mm, p < 0.05) in L4 vertebrae significantly. The present study indicates that the administration of RDE at higher doses over a 16-week period can prevent OVX-induced osteoporosis in rats without hyperplastic effects on the uterus. Conclusion: Thus, RDE is a potential natural alternative for postmenopausal osteoporosis treatment in elderly women.

Memory-enhancing effect of Rhodiola rosea L extract on aged mice

Purpose: The memory-enhancing effects of Rhodiola rosea L. extract (RRLE) on normal aged mice were assessed. Methods: In the open-field test, the effect of RRLE (150 and 300 mg/kg) on mouse locomotive activities was evaluated by investigating the extract’s influence on CAT and AchE activities in the brain tissue of mice. Results: Compared with aged group, high dose of RRLE reduced the total distance (3212.4 ± 123.1 cm, p < 0.05) significantly, increased catalase (CAT) activity (101.4 ± 12.2 U/mg pro, p < 0.05), and inhibited acetyl cholinesterase (AChE) activity (0.94 ± 0.12 U/mg pro, p < 0.05) in the brain tissue of aged mice. Conclusion: The results show that RRLE improves the memory functions of aged mice probably by increasing CAT activity while decreasing AChE activity.

Anti-hyperprolactinemic effect of Ficus pumila Linn extract in rats

Purpose: To investigate the anti-hyperprolactinemic effect of Ficus pumila Linn. extract (FPLE) in rats. Methods: Hyperprolactinemic rats were generated by subcutaneous injection of metoclopramide dihydrochloride (50 mg/kg). A high dose (800 mg/kg), moderate dose (400 mg/kg), or low dose (200 mg/kg) of FPLE was administered into the stomach of hyperprolactinemic rats for 30 days, after which serum sex hormones and pituitary prolactin-positive cell number and mRNA expression were measured. Results: FPLE had a significant effect on measures of hyperprolactinemia. Compared with hyperprolactinemic rats without FPLE treatment, hyperprolactinemic rats that received a high dose of FPLE showed altered serum estradiol, progesterone, prolactin, follicle-stimulating hormone, and luteinizing hormone levels (p < 0.05), as well as decreased pituitary prolactin-positive cell number (p < 0.05) and mRNA expression (p < 0.05). Conclusion: FPLE can potentially be used as an anti-hyperprolactinemia treatment but further studies are required to ascertain its suitability.

Effect of Astragalus membranaceus (Fisch) Bunge extract on streptozocin-induced diabetic in rats

Purpose: To investigate the effect of Astragalus membranaceus (Fisch.) Bunge. extract (AMBE) on streptozotocin-induced diabetic rats. Methods: The aqueous extract of AMB was obtained by steeping the dried Astragalus membranaceus (Fisch.) Bunge. in water at 60 oC three times, each for 1 h, before first drying in an oven at 100 oC and then freeze-drying the last extract thus obtained. Diabete model rats was induced by a single intraperitoneal injection of a freshly prepared solution of streptozotocin (50 mg/kg). The rats were randomly divided into 6 groups of ten rats each: negative control group, normal control group, reference group (glibenclamide1 mg/kgbody weight) as well as AMB extract groups, namely, 40, 80 and 160 mg/kg body weight. Antihyperglycemic effect was measured by blood glucose and plasma insulin levels. Oxidative stress was evaluated in liver and kidney by antioxidant markers, viz, lipidperoxidation (LPO), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT), while blood serum levels of creatinine and urea were also determined in both diabetic control and treated rats. Results: Compared with diabetic rats, oral administration of AMBE at a concentration of 160 mg/kg daily for 30 days showed a significant decrease in fasting blood glucose (109.438 ± 3.52, p < 0.05) and increased insulin level (13.96 ± 0.74, p < 0.05). Furthermore, it significantly reduced biochemical parameters (serum creatinine, 0.86 ± 0.29, p < 0.05) and serum urea (45.14 ± 1.79, p < 0.05). The treatment also resulted in significant increase in GSH (49.21 ± 2.59, p < 0.05), GPx (11.96 ± 1.16, p < 0.05), SOD (14.13 ± 0.49, p < 0.05), CAT (83.25 ± 3.14, p < 0.05) level in the liver and kidney of diabetic rats. Conclusion: The results suggest that AMBE may effectively normalize impaired antioxidant status in streptozotocin-induced diabetes in a dose-dependent manner. AMBE has a protective effect against lipid peroxidation by scavenging free radicals and is thus capable of reducing the risk of diabetic complications.

Effect of Dioscorea tokoro Makino extract on hyperuricemia in mice

Purpose: To investigate the anti-hyperuricemic effect of Dioscorea tokoro Makino extract (DTME) in potassium oxonate-induced hyperuricemic mice. Method: The effect of DTME was investigated in the hyperuricemic mice induced by potassium oxonate. DTME. The extract was administered to the mice daily at doses of 220, 440 and 880 mg/kg for 10 days; allopurinol (5 mg/kg) was given as positive control. Serum and urine levels of uric acid and creatinine were determined by colorimetric method. Simultaneously, protein levels of urate transporter 1 (URAT1) and organic anion transporter 1 (OAT1) in the rat kidney were analyzed by Western blotting. Results: Compared with control, a high dose of DTME inhibited xanthine oxidase (XOD) activity in both serum (18.12 ± 1.33 U/L) and in liver (70.15 ± 5.20 U/g protein) (p < 0.05); decreased levels of serum uric acid (2.04 ± 0.64 mg/L) (p < 0.05), serum creatinine (0.35 ± 0.18 μmol/L) and blood urea nitrogen (BUN) (8.83 ± 0.71 mmol/L) (p < 0.05). Furthermore, the extract increased levels of urine uric acid (38.34 ± 8.23 mg/L), urine creatinine (34.38 ± 1.98 mmol/L), down regulated of URAT1 and up regulated of OAT1 protein expressions (p < 0.05) in the renal tissue of hyperuricemic mice. Conclusion: DTME improves renal dysfunction in rats by regulating renal urate transporters in hyperuricemic rats. This may find therapeutic application in antihypertensive therapy.

Anti-osteoporosis effect of Cistanche deserticola Ma extract in ovariectomized rats

Purpose: To investigate the therapeutic effects of Cistanche deserticola Ma. extract (CDME) on ovariectomy-induced osteoporosis in rats. Methods: Female Sprague-Dawley rats were randomly assigned to a control group and five ovariectomy (OVX) subgroups, that is, OVX with vehicle (OVX), OVX with 17ß-estradiol (E2, 25 μg/kg/day), and OVX with CDME doses (40, 80, or 160 mg/kg/day). Daily oral administration of E2 or CDME started 4 weeks after OVX and lasted for 16 weeks. Bone mineral density (BMD) of L4 vertebrae and right femur of rats was estimated, The length of each femur was measured, and biochemical analysis of serum and urine specimens were performed. Results: CDME dose-dependently inhibited the reduction in BMD of L4 vertebrae (0.23 ± 0.02 g/cm3, p < 0.05) and femurs (0.20 ± 0.03 g/cm3, p < 0.05) caused by OVX and prevented the deterioration of trabecular microarchitecture (p < 0.05), which were accompanied by a significant decrease in skeletal remodeling (p < 0.05) as evidenced by the lower levels of bone turnover markers. Conclusion: This study indicates that CDME prevents OVX-induced osteoporosis in rats, and could be used for treating osteoporosis in elderly women.