Normal Male Rats Research Articles

Profil Reproduksi Jantan Tikus (Rattus norvegicus Berkenhout, 1769) Galur Wistar Stadia Muda, Pradewasa, dan Dewasa

Reproductive biology is one of prominent studies in biomedical research. Disruption in reproductive system becomes a major problem both in humans and animals. Preclinical study using animal model is therefore needed to initiate clinical studies and diagnostic purposes. Wistar rats are commonly used for research in male and female reproductive system due to their representation of mammal biological system. For that purpose, their reproductive age must be determined to meet the aim of studies. This research was carried out to provide reproductive profile of normal male Wistar rats from different ages, furthermore categorizing them into three checkpoints: young, subadult, and adult. Variables observed including: body mass, testosterone level, reproductive glands index, spermatogenesis, and sperm analysis. Results demonstrated that body mass, testosterone level, and reproductive glands index increase with age (significant at the age of 6–7 weeks). Spermatogenesis is initiated at the age of 7 weeks, characterized by significant increase in the number of spermatogenic cells which then maintained at subsequent ages. Spermatozoa has been produced at the age of 6 weeks, however still in low concentration, immotile, and not viable. The quantity and quality of sperm also increase with age. At the age of 8–9 weeks, sperm concentration significantly increases, progressive movement occurs, and viability is close to 100 %. In conclusion, rats aged 4–5 weeks can be categorized as young, sexually immature; rats aged 6–7 weeks are subadult, the reproductive system has well-developed (puberty) but spermatozoa are still immotile (infertile); rats aged 8–9 weeks are adult, sexually mature, and ready for mating, thus suitable as animal model for the study of reproductive system.Key words: Wistar rats, reproductive system, testosterone, spermatogenesis, spermatozoa.Â

ANTIHYPERGLYCEMIC AND ANTI-OXIDANT POTENTIAL OF ETHANOL EXTRACT OF VITEX THYRSIFLORA LEAVES ON DIABETIC RATS

Objective: Vitex thyrsiflora Baker (Verbenaceae) is a glabrous under shrub that is widely distributed in Cameroon. Diabetes is characterized by chronic hyperglycemia, a source of increased oxidative stress and tissue oxidative damage. The objective of current study was to estimate the antihyperglycemic and anti-oxidant potential of ethanol extract of Vitex thyrsiflora leaves on diabetic rats Methods: The antihyperglycemic effect of an ethanol extract of Vitex thyrsiflora leaves was investigated in normal male rats and streptozotocin induced diabetic male rats and its antioxidant potential was evaluated. After preparation of the extract, it was subjected to a phytochemistry screening, and tested on male rats made hyperglycemic in the Oral Glucose Tolerance Test (OGTT) and in streptozotocin diabetic rats. Glibenclamide (10 mg/Kg) was served as a positive control in both experiments. The evaluation of the antioxidant potential was done through the determination of the total polyphenols and total flavonoid contents, and by using the ferric reducing antioxidant power assay and the free radical scavenging activity on DPPH method. Results: The results show that the extract contains alkaloids, flavonoids, steroids, saponins and phenolic compounds. The test on hyperglycemic rats in OGTT showed that, the extract was effective (at a dose of 200 mg/Kg) to significantly decreased glucose-induced hyperglycemia (**p ˂ 0.01). The extract was ineffective on streptozotocin induced diabetic rats. The study of the antioxidant potential showed that, polyphenols and flavonoids increase with the concentration of the extracts. IC50 value was found to be 65.97, based on the log (inhibitor) vs. normalized response-Variable slope. Conclusion: FRAP appears to be significantly highly correlated with total polyphenols content and total flavonoids content. This shows that the ethanol extract of V. thyrsiflora leaves could be served to prevent acute hyperglycema, but not a chronic hyperglycemic state. Peer Review History: Received 10 June 2018; Revised 24 June; Accepted 4 July, Available online 15 July 2018 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Dr. Sabah Hussien El-Ghaiesh, Tanta University, Egypt, s.ghaiesh@gmail.com Prof. Dr. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, alialkaf21@gmail.com Similar Articles: COMPARATIVE CHARACTERIZATION OF ANTIOXIDANT PROFILE OF VITAMIN-E AND RED DATES IN PLACEBO AND TESTED GROUPS OF HYPERLIPIDEMIC PATIENTS

Preparation of dual-modality yttrium-90 radiolabeled nanoparticles for therapeutic investigation

Abstract Magnetic Fe3O4 nanoparticles with narrow size distribution were synthesized by simple and high yielded co-precipitation technique using ferrous salts with a molar ratio of Fe3+/Fe2+=2. After coating of the nanoparticles with Stöber silica (SiO2@Fe3O4), nanoparticles were functionalized by amine groups. Then chelator molecules diethylenetriaminepentaacetic (DTPA) and tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were coupled to the APTS-SiO2@Fe3O4 to chelating Y-90 radiometal that makes these nanoparticles a suitable agent for therapeutic application as dual-modality PET/MRI imaging. The results show the coupling of DTPA takes place better than DOTA. Synthesis of magnetic nanoparticles (MNPs) was followed by structure identification using XRD, SEM, TGA and IR techniques. In order to trace MNPs biodistribution, the radiolabeled MNPs-DTPA were prepared using 90Y (production of 90Y/90Sr generator) with a good labeling efficiency (about 92%, RTLS method). The biodistribution of the radiolabeled MNPs was checked in normal male rats up to 24 h compared to free Y3+. The data shows that the tracer accumulation is in reticuloendothelial tissue while the stability of the complex is highly retained.

Suppression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Function in Thalamocortical Neurons Prevents Genetically Determined and Pharmacologically Induced Absence Seizures.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and the Ih current they generate contribute to the pathophysiological mechanisms of absence seizures (ASs), but their precise role in neocortical and thalamic neuronal populations, the main components of the network underlying AS generation, remains controversial. In diverse genetic AS models, Ih amplitude is smaller in neocortical neurons and either larger or unchanged in thalamocortical (TC) neurons compared with nonepileptic strains. A lower expression of neocortical HCN subtype 1 channels is present in genetic AS-prone rats, and HCN subtype 2 knock-out mice exhibit ASs. Furthermore, whereas many studies have characterized Ih contribution to “absence-like” paroxysmal activity in vitro, no data are available on the specific role of cortical and thalamic HCN channels in behavioral seizures. Here, we show that the pharmacological block of HCN channels with the antagonist ZD7288 applied via reverse microdialysis in the ventrobasal thalamus (VB) of freely moving male Genetic Absence Epilepsy Rats from Strasbourg decreases TC neuron firing and abolishes spontaneous ASs. A similar effect is observed on γ-hydroxybutyric acid-elicited ASs in normal male Wistar rats. Moreover, thalamic knockdown of HCN channels via virally delivered shRNA into the VB of male Stargazer mice, another genetic AS model, decreases spontaneous ASs and Ih-dependent electrophysiological properties of VB TC neurons. These findings provide the first evidence that block of TC neuron HCN channels prevents ASs and suggest that any potential anti-absence therapy that targets HCN channels should carefully consider the opposite role for cortical and thalamic Ih in the modulation of absence seizures.SIGNIFICANCE STATEMENT Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play critical roles in the fine-tuning of cellular and network excitability and have been suggested to be a key element of the pathophysiological mechanism underlying absence seizures. However, the precise contribution of HCN channels in neocortical and thalamic neuronal populations to these nonconvulsive seizures is still controversial. In the present study, pharmacological block and genetic suppression of HCN channels in thalamocortical neurons in the ventrobasal thalamic nucleus leads to a marked reduction in absence seizures in one pharmacological and two genetic rodent models of absence seizures. These results provide the first evidence that block of TC neuron HCN channels prevents absence seizures.

Effect of Hydroalcoholic Extract of Capparis decidua (Forssk.) Edgew on Sexual Behavior of Male Rats

Capparis decidua has traditionally been recommended as an aphrodisiac agent. Although, it's medicinal use has not been scientifically proved. The present study therefore evaluated the effects of hydroalcoholic extract of C. decidua roots, stem and leaf on sexual behavior in normal male rats. The hydroalcoholic extract of C. decidua was administered (100 mg/kg, 200mg/kg) to different groups of male wistar rats for 28 days. The female rats were brought in estrous phase before the mating in each group of male rats. Standard group was administered sildenafil citrate at 5mg/kg orally for 28 days. Control group was administered only distilled water. All the experimental groups i.e C. decidua 100mg/kg, 200 mg/kg, per se group (only C. decidua 200 mg/kg), standard group(sildenafil citrate 5mg/kg) were compared with the control group for parameters evaluated for sexual behavior study. C. decidua at 100mg/kg, 200 mg/kg, and per se treated groups produced significant arousal of sexual activity in male rats. They significantly increased the frequencies of mount, intromission frequency. The mount latency and intromission latency were significantly reduced but ejaculation latency was prolonged significantly. The results indicated that hydroalcoholic extract of C. decidua enhanced sexual behaviour in male rats. The enhanced sexual behavior in male rats at the doses of 100 and 200 mg/kg body weight may be due to the presence of phytochemicals like alkaloids, saponins, flavonoids as these phytochemicals has role in increasing sexual strength, androgen enhancing, and antioxidant activity.

Nestin expression and invivo proliferative potential of tanycytes and ependymal cells lining the walls of the third ventricle in the adult rat brain.

There is a disagreement in the literature concerning the degree of proliferation of cells in the walls of the third ventricle (3rdV) under normal conditions in the adult mammalian brain. To address this issue, we mapped the cells expressing the neural stem/progenitor cell marker nestin along the entire rostrocaudal extent of the 3rdV in adult male rats and observed a complex distribution. Abundant nestin was present in tanycyte cell bodies and processes and also was observed in patches of ependymal cells as well as in isolated ependymal cells throughout the walls of the 3rdV. However, we observed very limited ependymal cell or tanycyte proliferation in normal adult rats as determined by bromodeoxyuridine (BrdU) incorporation or the expression of Ki-67. Moreover, fewer than 13% of the cells that were BrdU-positive (BrdU+) or Ki-67-positive (Ki-67+) expressed nestin. These observations stand in contrast to those made in the subventricular zone of the lateral ventricle (SVZ) and subgranular zone of the hippocampal formation (SGZ), where cell proliferation measured by BrdU incorporation or Ki-67 expression is observed frequently in cells that also express nestin. Thus, while ependymal cell or tanycyte cell proliferation can be promoted by the addition of mitogens, dietary modifications or other invivo manipulations, the proliferation of ependymal cells and tanycytes in the walls of the 3rdV is very limited in the normal adult male rat brain.

The Role of Angiotensin II Infusion on the Baroreflex Sensitivity and Renal Function in Intact and Bilateral Renal Denervation Rats.

Background:The role of renin-angiotensin system (RAS) in communication between renal system and cardiovascular system is extremely important. Baroreflex sensitivity (BRS) index defines as heart rate (HR) alteration versus mean arterial pressure (MAP) change ratio . Sympathetic nerve is arm of the baroreflexes and any change in its activity will lead to change in the BRS. The role of angiotensin II (Ang II) infusion in systemic circulation accompanied with bilateral renal denervation (RDN) on BRS index and renal function was studied.Materials and Methods:Seventy-two male and female Wistar rats in 12 groups were anesthetized and catheterized. The alteration of MAP and HR responses to phenylephrine infusion compared to control groups was determined in bilateral RDN rats subjected to treat with Ang II (300 or 1000 ng/kg/min) administration.Results:The BRS index was elevated in Ang II-treated non-RDN (normal) male rats gradually and dose dependently (P < 0.05), while this index was significantly different when compared with RDN male rats (P < 0.05). Accordingly, the BRS index was significantly lower in RDN than non-RDN male rats, and such observation was not observed in female rats. The creatinine clearance (insignificantly) and urine flow (significantly; P < 0.05) were decreased in both non-RDN and RDN male and female rats treated with Ang II. In RDN model, the serum nitrite levels were decreased in male and increased in female by Ang II infusion when compared with vehicle infusion.Conclusion:The Ang II infusion could increase the BRS index in non-RDN (normal) male rats which is significantly greater than BRS index in RDN rats.

Effect of Ethanolic Extract of Hyphaen thebaica (L) Seed on Some Haematological, Biochemical and Histological Features of Albino Rats

It is well known that many diseases throughout the world are well treated with medicinal plants which have great protective and therapeutic effects. The effect of crude ethanolic extract of Hyphaene thebaica (L) Mart (HT) on some hematologicalindices and some biochemical parameters in normal albino rats in addition to the histological studies on liver and kidney tissues of these rats were investigated. Thirty two normal white male albino rats were divided into four groups of eight rats/each group. Group one served as the control group, group 2, 3 and 4 served as the test groups for the crude ethanolic extract of HT seeds to which oral intubation of 100 mg/Kg, 200 mg/Kg and 400 mg/Kg dosages of the extracts were administered, respectively. All the rats were fed with normal diet and water ad-libitum for 21 days then after then, all groups were sacrificed, two blood samples were collected for haematological and biochemical parameters. Specimens from liver and kidney were collected for histopathological examination. Group (3; 200 mg/Kg) and group (4; 400 mg/Kg) revealed a significant increase (P≤ 0.05) increase in total WBCs, total RBCs, and haemoglobin concentration compared with the control. However, significant decrease (P ≤ 0.05) was observed in the level of cholesterol and triglycerides after treating with 400 mg/Kg dose only when compared with the control. There was no significant change in platelets count, liver functions (alanine transaminase (ALT), asparatate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), Albumin and total protein) and kidney functions (urea and creatinine).Histopathological results of taken liver and kidney tissues revealed no significant changes when compared with the control group. The crude ethanolic extracts of HT seeds hashypolipidimic effect and may be able to boost immune system.

Diabetic tubulopathy: effect of toll-like receptor 2, toll-like receptor 4, and nuclear factor κb in elderly type 2 diabetes mellitus patients

Objective The aims of the current study were to investigate the role of toll-like receptor (TLR)2, TLR4, and nuclear factor κB (NF-κB) expression in the pathogenesis of diabetic nephropathy (DN) in elderly type 2 diabetics, and also to determine the functional role of TLR2, TLR4, and NF-κB in tubular inflammation. Background Chronic kidney disease is one of the major complications of type 2 diabetes mellitus (T2DM) and is the leading cause of end-stage renal disease. There is growing evidence indicating that chronic low-grade inflammatory response is a recognized factor in the pathogenesis and progression of diabetic renal injury. Patients and methods Our study included a human part and an animal part, in the human part, participants were divided into four groups; old patients: 30 T2DM patients aged 65 years and above with documented DN in stage 2 incipient nephropathy and stage 3 overt nephropathy, old control: 20 age- matched and sex-matched healthy persons aged 65 years and above serving as a control group, young patients: 30 T2DM patients aged less than 65 years with documented DN in stage 2 incipient nephropathy and stage 3 overt nephropathy and young control: 20 age-matched and sex-matched healthy persons aged less than 65 years serving as a control group. We took a full history of all patients and concluded complete physical examination. Mean arterial pressure, BMI and fundus examination were done. We measured fasting plasma glucose, 2 h postprandial plasma glucose, glycated haemoglobin, complete urine analysis, serum creatinine, blood urea nitrogen, C-reactive protein, urinary albumin/creatinine ratio, estimated glomerular filtration rate using Modification of Diet in Renal Disease Abbreviated Equation, level of TLR2, TLR4, and nuclear NF-κB. In the animal part, the study was conducted on 20 aged (1.5-year old) male wistar rats, the rats were divided into two main groups; group I (control): 10 normal healthy male rats, group II (diabetic): 10 rats with high-fat diet)/streptozotocin-induced diabetes. Blood samples were collected for the determination of fasting plasma glucose, fasting serum insulin, insulin resistance was assessed by calculating the homeostatic model assessment of insulin resistance, blood urea nitrogen, serum creatinine and C-reactive protein and analysis of TLR2, TLR4, and NF-κB in renal tissue was done. Results In the human part of our study: the level of TLRs2, TLR4, and NF-κB was significantly higher in old diabetic patients group than young diabetic patients group and control group. In the animal part of our study: the level of TLRs2 and 4 and NF-κB was significantly higher in diabetic rat group than healthy rat control group. Conclusion TLRs2, TLR4, and NF-κB were higher in old diabetic patients compared with young diabetic patients and normal individuals. These observations significantly added to the emerging role of TLRs in T2DM development and its possible role in the pathogenesis and progression of DN. Also, the present study showed that the TLR system was closely related to the ageing of the kidneys.

THE AMELIORATING ROLE OF Alpha-LIPOIC ACID SUPPLMENTATION ON ADVERSE EFFECTS INDUCED BY LEAD ACETATE IN BOTH THE HIPPOCAMUS AND THE CEREBRAL CORTEX OF THE MALE ALBINO RATS

The present study focused on two brain areas hippocampus and the cerebral It was designed to investigate the possible mechanisms involved in Lead acetate neurotoxicity and the potential protective effects of α-lipoic acid (α-LA), as an antioxidant against lead-induced neurotoxicity. Fourty adult male albino rats Rattus rattus (each weighing 130 ± 10 g) were divided into four groups (n=8): 1- Normal control group; C: Normal male rats fed ad libitum and allowed a free access of water, and were kept without any treatments. 2- Initiation group (lead-acetate control group; A): Normal male rats received Lead acetate in an interperitoneal dose of 20 mg/kg b.wt daily for two weeks. 3- Treatment group (α-lipoic acid control group; B): Normal male rats were intraperitoneally injected with α-lipoic acid in a dose of 20 mg/kg b.wt daily for three weeks. 4- Pre-initiation treatment group (prophylactic group; D): Normal male rats were intraperitoneally injected with α-Lipoic acid in a dose of 20 mg/kg b.wt daily for one week and then received the above-mentioned dose of the lead acetate for other two successive weeks together with the same dose of α-lipoic acid. 5- Post-initiation treatment group (therapeutic group; E): Normal male rats were intraperitoneally injected once daily with lead acetate (20 mg/kg b.wt) for two weeks then were intraperitoneally injected with α-lipoic acid in a dose of 20 mg/kg b.wt daily for successive three weeks. The levels of lipid peroxidation as malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH), nitric oxide level (NO), and serotonin (5- HT) were estimated in the selected brain regions, the hippocampus and the cerebral cortex, of adult male albino rats in the different groups. These biochemical variables were supported by histopathological examinations by using H&E and toluidine blue staining. Results showed that administration of lead acetate led to enhancement of lipid peroxidation and increased PCC with a concomitant reduction in GSH levels and NO production. In addition, the levels of 5-HT decreased in the hippocampus and the cerebral cortex. However, the administration of α-LA showed a protective effect against Lead acetate-induced neurotoxicity. Rats treated with α-LA showed a corresponding decrease in lipid peroxidation and PCC level. Furthermore, there was an increase in brain GSH level, NO production and level of 5-HT in both brain regions hippocampus and the cerebral Histological studies showed that Lead acetate caused different degrees of neuronal degeneration, focal gliosis, pyknotic neurons, oedema in meninges, cerebral neuropil vacuolization and degenerations. The rats treated with α-lipoic acid revealed an improvement in the histopathological alterations induced by Lead acetate. Finally, the data showed that α-LA has an effect when administered as a therapeutic drug more than as a prophylactic one.

Effects of Pinealectomy and Gonadectomy on Olfactory Bulb Dopaminergic Neurons in Rats.

Background:Olfactory disorder is an early manifestation of Parkinson's disease (PD), likely to be associated with abnormalities of the dopaminergic neurons in the olfactory bulb (OB); however, the causes of olfactory disorder in PD are not entirely clear. Some studies showed that melatonin (MT) and androgens (mainly testosterone, T) might participate in the pathogenesis of PD. The research aimed to investigate effects of MT or T deficiency on OB dopaminergic neurons in rats.Methods:One hundred and twenty normal male Wistar rats were randomly divided into the control, sham operation pinealectomy (PX), sham operation gonadectomy (GDX), PX, GDX, and PX + GDX groups. After 60 days, glial cell hyperplasia and neuronal apoptosis were examined with hematoxylin and eosin and the TUNEL method; the expression levels of tyrosine hydroxylase (TH), Bax, and Bcl-2 were measured using immunohistochemistry (IH) by the streptavidin peroxidase conjugated method. Comparison among multiple sets used analysis of variance and LSD method or Kruskal-Wallis test and Nemenyi method.Results:There were no significant differences between the sham operation groups and the control group; thus, they were merged into Group A. There was no significant glial cell hyperplasia (P > 0.05) or change in shape in any of the groups after PX or GDX. The number of apoptotic cells in Groups A (1.41 ± 0.56), PX (12.31 ± 4.68), GDX (20.52 ± 5.13), and PX + GDX (30.23 ± 5.25) successively significantly increased (P < 0.05). The number of TH (+) cells in Groups A (42.62 ± 5.63), PX (37.31 ± 4.32), GDX (31.07 ± 4.21), and PX + GDX (25.22 ± 3.66) was successively significantly decreased (P < 0.05). The gray value of TH (+) cells and fibers in Groups A (98.51 ± 10.36), PX (108.96 ± 13.01), GDX (119.02 ± 12.98), and PX + GDX (128.99 ± 13.39) was successively significantly increased (P < 0.05). The results of Bax staining were as follows: Group A+, Group PX++, Group GDX++, and Group PX+ GDX+++, the results of Bcl-2 in all groups were +.Conclusions:PX or GDX could lead to OB neurotoxicity in the following groups of rats in the following order: PX < GDX < PX + GDX. PX or GDX increased the ratio of Bax/Bcl-2. The effect of PX and GDX was equal, but both were less than that of PX + GDX. Neurotoxicity as a result of PX or GDX was not related to inflammation.

Effectiveness of Amygdalus mongolica oil in hyperlipidemic rats and underlying antioxidant processes

ABSTRACTThe seeds of Amygdalus mongolica contain various constituents including flavonoids and vitamin E, which are known to exert antioxidant effects. However, the safety of the oil extract of this compound is not fully known. The aim of this study was to determine the physicochemical properties of A. mongolica oil, identify the constituents and subsequently assess the effectiveness of utilizing this seed extract in hyperlipidemia as an antioxidant agent. In particular, the toxicity and safety of A. mongolica oil were examined with emphasis on effects on blood lipids level and serum lipid peroxidation using a hyperlipidemia rat model. Treatment with 20 ml/kg A. mongolica oil produced no apparent adverse effects after 14 days in normal female and male rats. A dose of 2.5–10 ml/kg A. mongolica oil administered to hyperlipidemic male rats significantly decreased serum total cholesterol (TC), low-density lipoprotein-C (LDL-C), malondialdehyde (MDA), total cholesterol high-density lipoprotein-C (TC/HDL-C), LDL-C/HDL-C, and atherosclerosis index(AI). In contrast, glutathione (GSH) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased. Data demonstrated that A. mongolica oil may be utilized in conditions of hyperlipidemia due to its antioxidant effects.

28-Homocastasterone down regulates blood glucose, cholesterol, triglycerides, SREBP1c and activates LxR expression in normal & diabetic male rat

Plant steroids are being recognized as influential secondary bio factors, assimilating in animal tissues through diet and affecting their cellular metabolic function to varying degree. They modulate catalytic and signaling functions in mammalian cells, affecting cellular homeostasis. The effect of phyto brassinosteroid ketoisoform 28-homocastasterone (28-HC), was assessed for its influence on blood glucose, plasma lipid and selective signal marker levels in normal and diabetic male wistar rat models. A 15 day oral feed regimen employing the experimental rat, noted that circulating blood glucose, cholesterol and triglyceride level in diabetic rat were markedly reduced by this compound. This study confirmed that the keto form had anti-hyperglycemic and anti-lipidemic potency associated with it and was available to man and animals in their diet. Western blots of marker protein, PCR amplicons of marker mRNA expressions and In Silico studies suggested that 28-HCeffect is being mediated through LxR molecular operatives in the rat cell.

Screening of Antidiabetic Activity of Extract and Fraction of Biophytum sensitivum in Rats Using STZ-Nicotinamide Induced Diabetes Model

The study was aimed at investigate the effect of methanolic extract of Phaseolus semierectus(L.) (Leguminosae) on general mating behaviour, libido, and adverse effects on sexually normal male albino rats. Methanolic extract was administered orally at the dose of 100, 200, and 400 mg / kg, to different groups of male rats (n = 8) once a day for 14 days. All the doses resulted in significant increase in mount frequency, intromission frequency and anogenital sniffing when compared to normal. The methanolic extract of Phaseolus semierectus (L.) seeds at higher concentration (400 mg/kg body weight) showed significant aphrodisiac activity on male Wister albino rats as evidenced by an increase in number of mounts and mating performance. Thus, in experimental rats, the results of the present study suggest that the methanolic extracts of Phaseolus semierectus (L.) exert significant aphrodisiac activity.

Central effects of insulin detemir on feeding, body weight, and metabolism in rats.

Insulin detemir (DET) is a basal insulin analog that, in contrast to other long-acting forms of insulin, has significant weight-gain-sparing effects in diabetic patients. We hypothesized that this effect of DET may be due to its enhanced catabolic action in the central nervous system. We investigated the long-term effects of single third ventricular (3V) microinjections of equimolar doses of DET and regular insulin in normal male rats on feeding, body weight, energy expenditure (EE), and respiratory quotient (RQ). Also, in acute testing, we assessed the ability of lower doses of DET to alter feeding, EE, and RQ when microinjected directly into the paraventricular nucleus (PVN). The anabolic peptide ghrelin served as a positive control in acute testing. 3V administration of both DET (0.5-2.0 mU) and regular insulin (2.0-8.0 mU) significantly reduced feeding and body weight over 48 and 120 h, respectively, with DET yielding greater inhibitory effects. DET also stimulated greater elevations of EE and reductions of RQ over 72 and 48 h postinjection, respectively. In acute (4 h) testing, microinjections of DET (0.5 mU) into the PVN reduced feeding, increased EE, and reduced RQ, while ghrelin (100 pmol) had the opposite effects. When administered sequentially into the PVN, DET (0.25 and 0.5 mU) reversed ghrelin-induced feeding, EE, and RQ effects. These data support the notion that the weight-sparing effect of DET is at least in part based on its central catabolic action and that enhanced EE and reduced RQ may participate in this effect.

EXTRACORPOREAL BLOOD Aβ REMOVAL SYSTEM (EBARS) REDUCED SOLUBLE Aβ IN THE BRAIN BY TRIGGERING INFLUX INTO THE BLOOD: RAT STUDIES

Rapid removal of Aβ from the blood by an extra-corporeal system may act as a peripheral sink from the brain. We have reported that 1) several medical materials including hemodialyzers are able to remove Aβ effectively, 2) the concentrations of blood Aβs decreased and Aβ influx into blood were triggered during hemodialysis in humans, 3) Aβ deposition in the brain of hemodialysis patients was significantly lower than controls. Here, the effect of removing blood Aβ on blood and cerebrospinal fluid (CSF) concentrations of Aβ was investigated in rats. This study was approved by the Institutional Animal Care and Use Committee in Education and Research Center of Fujita Health University. The blood of normal SD male rats (9–11weeks, n=8) was treated for 60 minutes extracorporeally with mini-columns of hexadecyl-alkylated cellulose beads (HDC) as Aβ removers. Blood was collected at pre/post of the HDC-columns and CSF from Cisterna magna. The Aβ1–40 and Aβ1–42concentrations were measured by sandwich ELISAs (WAKO, Japan). The removal efficiencies of the blood Aβs by HDC-columns were 98% at 30min and 83% at 60min for Aβ1–40, 96% at 30min and 94% at 60min for Aβ1–42 during blood purification. Despite such high removal efficiencies, the blood Aβ concentrations at the end of blood Aβs removal (60min) in the whole body circulation significantly “increased” up to 153% for Aβ1–40 and 187% for Aβ1–42 (both, p=0.0003) compared with those just before the treatment. Further, Aβ concentrations in CSF decreased to 77% for Aβ1–40 (p=0.022) and 90% for Aβ1–42 (p=0.27). The decrease tendency of CSF Aβs continued another 60min; 64% for Aβ1–40 (p=0.071) and 77% for Aβ1–42 (p=0.25) compared with those before the treatment. Removal blood Aβ may trigger the influx from the brain into the blood. This might explain few Aβ depositions in the brains of hemodialysis patients. Therefore, Extracorporeal Blood Aβ Removal Systems may be potential therapeutic systems for Alzheimer's Disease. Acknowledgment: The authors thank Mrs. Kota Watanabe, Hiroki Aoki, and Ms. Yuri Sakakibara for their technical assistance. This work was partly supported by KAKENHI (2350531, 26282126) and Smoking Research Foundation.

Development of long-acting ciliary neurotrophic factor by site-specific conjugation with different-sized polyethylene glycols and transferrin

To overcome the deficiency of rapid elimination from blood, the truncated human recombinant ciliary neurotrophic factor was formulated by site-specific attachment of different-sized PEG-maleimide or by cross-linking with human transferrin through a hetero-bi-functional PEG linker (NHS-PEG5k-MAL). The PEGylated CNTF was purified by a two-step chromatography procedure and the transferrin coupling CNTF conjugate was separated through an elegant protocol. The conjugation site on CNTF was identified by peptide mapping analysis and validated that the linkage of the conjugates was specifically happened to Cys17 residue. Although both PEGylated and transferrin coupling CNTF demonstrated decreased cell based residual activity, markedly enhanced pharmacokinetic behaviors in normal male Sprague-Dawley rats were observed, especially for the PEG40k-CNTF with approximately 58-times improvement compared with the unmodified counterpart. The evaluation of the in vivo potency of body weight-losing was performed with normal male C57BL6 mice and the results revealed that both PEGylation and transferrin coupling could achieve improved therapeutic benefits relative to that of CNTF. Besides, PEG20k/40k-CNTF demonstrated more effective than transferrin coupling CNTF (Tf-PEG5k-CNTF) despite that the later showed preferable pharmacokinetic profile and cell based residual activity compared with PEG20k-CNTF. Weekly subcutaneous administration of PEG40k-CNTF with 0.5mg/kg and 1.0mg/kg dose resulted in approximately 35% and 50% decrease in food intake during one interval period of injection, indicating that PEG40k-CNTF is the most potential anti-obese agent for therapeutics.

COMPARATIVE ORCHIDOTOXICITY STUDY BETWEEN CHLOROQUINE PHOSPHATE AND HYDROXYCHLOROQUINE SULFATE ON ADULT ALBINO RATS

Introduction: Chloroquine phosphate (CQP) and hydroxychloroquine sulfate (HCS) are antimalarial drugs commonly used for treatment of malaria and numerous rheumatic diseases. Their widespread prescriptions may accompany with prolonged duration of therapy and higher daily dosages, leading to several toxic effects, including disturbance of reproductive system. Aim of the study: The present study was designed to compare the effect of six-week exposure to CQP and HCS on reproductive function of adult male albino rats. Materials and Methods: The study was conducted on 30 normal adult male albino rats divided equally into 3 groups (10 rats each), the Control-group (C-group) was given 1 ml of distilled water orally, whereas the CQPgroup (62 mg/kg/b. wt. ) and HCS-group (124 mg/kg/b. wt. ) were given single daily oral doses equivalent to 1/10th of LD50 of each drug for 6 consecutive weeks then all animals sacrificed. The serum levels of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH), quality of epididymal sperm (count, motility, viability, and morphology), degeneration severity of seminiferous tubules (SNT) and Leydig cells count per each animal, semi-quantitative scoring of SNT and Leydig cells histopathological changes, spermatogenesis maturity levels, and structural and ultrastructural morphologies of tissues were estimated. Results: The CQP-group showed severe orchidotoxic effects as manifested by statistically significant reductions in final weight gains of body, testes, and epididymis, all sperm quality, and all hormone levels, marked increases in the number of animals associated with SNT degeneration and reduced Leydig cells count, statistically significant increases in abnormalities of SNT and Leydig cells architectures, statistically significant decrease of spermatogenesis maturity levels, and extensive structural and ultrastructural changes in testicular parenchyma and interstitial tissues as compared to C-group and HCS-group. While, HCS-group displayed minor orchidotoxic effects as evidenced by insignificant changes in most of the evaluated parameters, significant reductions of LH and FSH levels, slight increases in the number of animals accompanied with SNT degeneration and reduced Leydig cells count, and minor changes of structural and ultrastructural testicular tissue architectures as compared to C-group. Conclusion, these results suggest that CQP has more orchidotoxic effects than HCS, and in terms of therapeutic usage, physicians should better prescribe HCS as it appears safer than CQP. Also, assessment of male reproductive functions should be done periodically for patients receiving both drugs for prolonged time, especially CQP, as they may induce endocrine disruptions.

PROTECTIVE EFFECT OF LEMONGRASS (CYMBOPOGON CITRATUS) AND VITAMIN E ON SODIUM VALPROATE INDUCED TESTICULAR TOXICITY IN RATS

Abstract The present study was carried to investigate the effect of extract and powder of Cymbopogon citrates and vitamin E on the sexual hormonal profiles against testicular toxicity of sodium valproate of normal male rats. The forty two mature male albino rats were divided into seven groups every group of 6 rats. The group control received fed on basal diet, whereas the other five groups received sodium valproate (positive group) the other four groups received Vit. E orally at a dose of (200 mg/kg b.wt./day), Lemongrass powder (100 mg/kg/diet/day), Lemongrass extract (10 ml/kg/b.wt/rat/day), vitamin E with lemongrass powder and vitamin E with lemongrass extract, for a period of 6 weeks, caused a significant increase in serum HDL-c, testosterone, serum follicle stimulating hormone level (FSH) ,luteinizing hormone (LH), total antioxidants , superoxide dismutase and glutathion levels compared to positive control group. Effect on in serum total cholesterol, triglycerides, LDL-c, sexual organs weight (testis, prostate, and seminal vesicles), malondialdehyde were also determined, and was found to be significantly lower in all the administered groups when compared with sodium valproate group. Findings in this study showed that lemongrass powder and extract combination with vitamin E has a potent protective effect against sodium valproate-induced testicular injury in rats. It also did not exert oxidative damage to the sexual organs and the various hormonal profiles as well as its relative safety and possible use to protect from sodium valproate side effects. Keywords: Cymbopogon citrates - Sodium valproate - Phenolic compounds - Seminal vesicles - Testicular toxicity.

Evaluation of Aphrodisiac Activity of Phaseolus semierectus (L.)Seeds

The study was aimed at investigate the effect of methanolic extract of Phaseolus semierectus(L.) (Leguminosae) on general mating behaviour, libido, and adverse effects on sexually normal male albino rats. Methanolic extract was administered orally at the dose of 100, 200, and 400 mg / kg, to different groups of male rats (n = 8) once a day for 14 days. All the doses resulted in significant increase in mount frequency, intromission frequency and anogenital sniffing when compared to normal. The methanolic extract of Phaseolus semierectus (L.) seeds at higher concentration (400 mg/kg body weight) showed significant aphrodisiac activity on male Wister albino rats as evidenced by an increase in number of mounts and mating performance. Thus, in experimental rats, the results of the present study suggest that the methanolic extracts of Phaseolus semierectus (L.) exert significant aphrodisiac activity.