Hypouricemic Actions of Exopolysaccharide Produced by Cordyceps militaris in Potassium Oxonate-Induced Hyperuricemic Mice

The hypouricemic actions of exopolysaccharide produced by Cordyceps militaris (EPCM) in potassium oxonate-induced hyperuricemia in mice were examined. Hyperuricemic mice were administered intragastrically with EPCM (200, 400 and 800 mg/kg body weight) or allopurinol (5 mg/kg body weight) once daily. Serum uric acid, blood urea nitrogen and liver xanthine oxidase (XOD) activities of each treatment were measured after administration for 7 days. EPCM showed dose-dependent uric acid-lowering actions. EPCM at a dose of 400 mg/kg body weight and allopurinol showed the same effect in serum uric acid, blood urea nitrogen and liver XOD activities in hyperuricemic mice. An increase in liver XOD activities was observed in hyperuricemic mice due to administration of EPCM at a dose of 200 mg/kg body weight. EPCM at a dose of 800 mg/kg body weight did not show significant effects on serum uric acid and XOD activities. We conclude that EPCM has a hypouricemic effect caused by decreases in urate production and the inhibition of XOD activities in hyperuricemic mice, and this natural product exhibited more potential efficacy than allopurinol in renal protection.     

Carvacrol partially reverses symptoms of diabetes in STZ-induced diabetic rats

Little is known about the protective effects of carvacrol on the symptoms of streptozotocin induced diabetes in rats. Hence, this present study was designed to evaluate the protective effect of the strong antioxidant, carvacrol, on the symptoms of streptozotocin induced diabetes in rats. Carvacrol at the doses of 25 and 50 mg/kg body weight were orally administered to diabetic rats for a period of 7 days after the onset of diabetes. Food-water intake and body weight changes were daily recorded. Biochemical parameters such as serum glucose, insulin, total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were measured. Although treatment of diabetic rats with oral administration of carvacrol resulted in a slight reduction in serum glucose level and significant reduction in serum total cholesterol, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase in comparison with diabetic control rats, there were no significant differences in serum insulin levels, food-water intake values and body weight changes. Despite the inadequacy of carvacrol on diabetes treatments, it was determined to have at least a partially protective role on liver enzymes.     

Decorporation of Iron Metal Using Dialdehyde Cellulose-Deferoxamine Microcarrier

Deferoxamine iron chelator has a limited therapeutic index due to rapid clearance from blood and possesses dose-limiting toxicity. Therefore, an intravenous deferoxamine delivery system based on dialdehyde cellulose (DAC) polymer was developed and its efficacy and toxicity were tested in iron-overloaded animals. The amino groups of deferoxamine were conjugated to free aldehyde moieties of dialdehyde cellulose via Schiff base reaction to form dialdehyde cellulose-deferoxamine (DAC-DFO) conjugate and characterized by Fourier transform infrared spectrophotometer, scanning electron microscope, and X-ray diffraction. The toxicity of prepared formulation was analyzed by XTT cell viability assay and LD50 study in mice. The change in serum iron levels, after intravenous administration of formulation, was observed in iron-overloaded rats. The DAC-DFO conjugate was tagged with Tc-99m to study the blood kinetics and observe change in blood circulation time. DAC-DFO conjugate was dispersible in water at concentration ～75 mg/ml. In vitro cytotoxicity assay and LD₅₀ study in mice indicated significantly enhanced safety of covalently bound deferoxamine (at >1000 mg/kg body weight compared to free drug at ～270 mg/kg dose). A preliminary scintigraphy imaging and blood clearance study, with technetium-99m, indicated prolonged circulation of conjugated DFO in rabbit blood. A single dose of formulation injected into iron overloaded animals was found to maintain the normal serum iron levels until 10 days. The polymeric conjugate was effective in maintaining normal serum iron levels until 10 days at a dose of 100 mg/kg body weight.     

In Vivo Assessment of Immunogenicity and Toxicity of the Bacteriocin TSU4 in BALB/c Mice

Bacteriocin TSU4 is a novel antimicrobial peptide isolated from Catla catla gut isolate Lactobacillus animalis TSU4. It has been reported for its potential antimicrobial activity against fish pathogens and food spoilage bacteria. In vivo safety evaluation is necessary to determine its immunogenicity, toxicity, and importance in real-life applications. The present study was designed to evaluate the immunogenicity, acute and sub-chronic toxicity of bacteriocin TSU4 in BALB/c mice to ensure its safety in industrial application. Male BALB/c mice were administered intraperitoneally for immunogenicity assessment, by oral gavage with 50, 100, and 200 mg/kg/body weight for acute test and 0.5 mg/kg/day dose of bacteriocin TSU4 for sub-chronic toxicity test. Neither mortality nor any infections were observed during experimental period. There was no major increase in antibody titer during the immunogenicity test, and no mortality was observed during acute or sub-chronic toxicity tests. The LD₅₀ value of bacteriocin TSU4 was found to be higher than 200 ± 0.45 mg/kg. No significant change in the serum biochemical markers, histopathological analysis and visual observation in spleen sizes was observed. These findings revealed that bacteriocin TSU4 is a non-immunogenic, safe, non-toxic, and could be a potential candidate for industrial applications in food preservation and aquaculture industries.     

Effects of vitamin C on the hypobaric hypoxia-induced immune changes in male rats

Hypobaric hypoxia (HH) induces oxidative stress (OS) and is associated with the generation of reactive oxygen species (ROS). Vitamin C is an efficient antioxidant, and it is used in a high-altitude environment to reduce the OS. The present study explores the role of vitamin C on some HH-induced changes of immune parameters in rats which were exposed to HHc condition at 18,000 ft in a simulated chamber for 8 h/day for 6 days with and without vitamin C administration at three different doses (200, 400, and 600 mg/kg body wt). The phagocytic activity of circulating blood WBC was increased, and the cytotoxic activity of splenic mononuclear cell (MNC) and the delayed type of hypersensitivity (DTH) responses to bovine serum albumin (BSA) were decreased in rats exposed to HHc condition, but these immune changes were blocked after administration of vitamin C at 400 mg/kg body wt. The leukocyte adhesive inhibition index (LAI) was not altered either in HHc condition or after administration of vitamin C in HHc condition. The serum corticosterone (CORT) concentration was increased in rats exposed to HHc condition which was blocked after administration of vitamin C (400 mg/kg body wt). The immune parameters and serum CORT concentration, however, did not show any recovery after administration of vitamin C at the dose of 200 and 600 mg/kg body wt. The present study indicates that administration of vitamin C at a dose of 400 mg/kg body wt may prevent the HH-induced immunological changes but not at the lower dose (200 mg/kg body wt) or higher dose (600 mg/kg body wt) in rats.     

Ascorbic acid is superior to silymarin in the recovery of ethanol-induced inflammatory reactions in hepatocytes of guinea pigs

Both oxidative stress and inflammatory reactions play a major role in alcoholic liver fibrosis. We evaluated the efficacy of ascorbic acid (AA) and silymarin in the regression of alcohol-induced inflammation in hepatocytes of guinea pigs (Cavia porcellus). Animals were administered with ethanol at a daily dose of 4 g/kg body weight (b.wt) for 90 days. On the ninety-first day, ethanol administration was stopped and animals were divided into alcohol abstention group and silymarin- (25 mg/100 g b.wt) and AA- (25 mg/100 g b.wt) supplemented groups and maintained for 30 days. There was a significant increase in the activities of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase in the serum of the ethanol group. The intracellular reactive oxygen species (ROS) and expressions of cytochrome P4502E1 and nuclear factor κB1, tumor necrosis factor-α, and transforming growth factor-β₁ in hepatocytes were significantly increased in ethanol group. The fibrotic markers α-smooth muscle actin and α ₁(I) collagen and activity of cytotoxicity marker caspase-3 were significantly increased and AA content was significantly reduced in hepatocytes of alcohol-treated guinea pigs. But the AA and silymarin supplementation significantly reduced these changes in comparison with alcohol abstention group. AA could induce greater reduction of inflammatory and fibrotic markers in hepatocytes than silymarin. This indicates that AA is superior to silymarin in inhibiting intracellular ROS generation and thereby reducing the ethanol-induced inflammation in hepatocytes.     

Combined Effects of Phytoestrogen Genistein and Silicon on Ovariectomy-Induced Bone Loss in Rat

This study was performed to evaluate the effect of concomitant supplementation of genistein and silicon on bone mineral density and bone metabolism-related markers in ovariectomized rat. Three-month-old Sprague Dawley female rats were subjected to bilateral ovariectomy (OVX) or sham surgery, and then the OVX rats were randomly divided into four groups: OVX-GEN, OVX-Si, OVX-GEN-Si, and OVX. Genistein and silicon supplementation was started immediately after OVX and continued for 10 weeks. In the OVX-GEN group, 5 mg genistein per gram body weight was injected subcutaneously. The OVX-Si group was given soluble silicon daily in demineralized water (Si 20 mg/kg body weight/day). The OVX-GEN-Si group was given subcutaneous injections of 5 mg genistein per gram body weight, at the same time, given soluble silicon daily (Si 20 mg/kg body weight/day). The results showed that the genistein supplementation in the OVX rats significantly prevented the loss of uterus weight; however, the silicon supplementation showed no effect on the uterus weight loss. The lumbar spine and femur bone mineral density was significantly decreased after OVX surgery; however, this decrease was inhibited by the genistein and/or silicon, and the BMD of the lumbar spine and femur was the highest in the OVX-GEN-Si-treated group. Histomorphometric analyses showed that the supplementation of genistein and/or silicon restored bone volume and trabecular thickness of femoral trabecular bone in the OVX group. Besides, the treatment with genistein and silicon for 10 weeks increased the serum levels of calcium and phosphorus in the OVX rats; serum calcium and serum phosphorus in the OVX-GEN-Si group were higher than those in the OVX-GEN and OVX-Si group (P < 0.05). At the same time, the treatment with genistein and/or silicon decreased serum alkaline phosphatase (ALP) and osteocalcin, which were increased by ovariectomy; serum ALP and osteocalcin in the OVX-GEN-Si group were lower than those in the OVX-GEN and OVX-Si groups (P < 0.05). The results above indicate that genistein and silicon have synergistic effects on bone formation in ovariectomized rats.     

Acute and sub-acute toxicity of ethanolic extract of Canthium mannii Hiern stem bark on Mus musculus

Acute and sub-acute toxicity of ethanolic extract (ETE) of C. mannii was assessed on white mice (Mus musculus). After 48 h of extract administration, no death was registered. It was deduced that the LD50 was indisputably higher than 16 g/kg body weight. The sub-acute toxicity test was based on the daily administration of three doses of ETE (300, 600 and 1200 mg/kg body weight) for four weeks; 1% DMSO served as negative control. As for the first experiment, no sign of toxicity was registered. Conversely, the sub acute doses stimulated and increased the weight-rate of mice after 7 days of treatment. Except for the spleen weight, the doses administrated did not modify the weight index. It was observed that, subacute doses induced and increased (a) the food (particularly) and water consumption according to time and (b) the number of red and white blood cells. It was thought that, ETE can stimulate the haematopoietic function. Finally, no time variation of the activity of alanine aminotransferase and aspartate aminotransferase enzyme was observed in the serum of euthanized mice. The results showed the innocuity of ETE of C. mannii and thus validated his utilization in cameroonian traditional pharmacopoea.     

Evaluation of hematological and hepatorenal functions of methanolic extract of Moringa oleifera Lam. root treated mice

Methanolic extract of M. oleifera root was found to contain some alkaloids (total alkaloid 0.2%). Effects of multiple weekly (35, 46, 70 mg/kg) and daily therapeutic (3.5, 4.6, 7.0 mg/kg) i.p. doses of the crude extract (CE) on liver and kidney functions and hematological parameters in mice were studied. No alteration in hematological and biochemical parameters at low and moderate dose level of daily and low dose level of weekly treatment of the extract was observed. However, the extract at moderate dose level in weekly treatment changed serum aminotransferase and plasma cholesterol levels significantly. High dose in addition to the above parameters changed total bilirubin, non protein nitrogen, blood urea and plasma protein. High dose of daily treatment and moderate and high dose of weekly treatment of CE increased WBC count and decreased clotting time significantly. The results indicate that the weekly moderate and high dose (> 46 mg/kg body wt.) and daily/therapeutic high dose (7 mg/kg) of CE affects liver and kidney functions and hematological parameters whereas the weekly dose (3.5 mg/kg) and low and moderate daily/therapeutic dose (3.5 and 4.6 mg/kg) did not produce adverse effects on liver and kidney functions.     

Assessment of the mutagenic activity of aversectin C]

Aversectin C was evaluated for mutagenic activity in the Ames test with Salmonella typhimurium TA 97, TA 98 and TA 100, in the dominant lethal assay on uninbred albino rats in a dose of 2.25 mg/kg body weight (1/40 of the LD50) and in the metaphase test on F1CBAxC57BI/6 mice in a dose of 8.2 mg/kg body weight (1/5 of the LD50). The agent showed no mutagenic activity in any of the tests. The anaphase test on F1CBAxC57BI/6 mice revealed no antimitotic activity of aversectin C.     

The protective effect of misoprostol against doxorubicin induced liver injury

ABSTRACT

We investigated the potential hepatoprotective effects of misoprostol (MP) on doxorubicin (DOX) induced liver injury in rats using histology and biochemistry. We used 21 male Sprague-Dawley rats divided randomly into three groups: group 1, control; group 2, DOX; group 3, DOX + MP. The control group was injected intraperitoneally (i.p.) with 0.5 ml 0.9% w/v NaCl and given 1 ml 0.9% NaCl orally for 6 days. DOX was administered i.p. as a single dose of 20 mg/kg. MP, 0.2 mg/kg, was given orally for 6 days. Treatment with MP increased high density lipoprotein cholesterol levels and decreased serum alanine aminotransferase, aspartate aminotransferase, low density lipoprotein cholesterol, triglycerides and total cholesterol levels significantly in serum. Increased malondialdehyde level and decreased catalase, glutathione and superoxide dismutase levels caused by DOX were suppressed significantly in liver tissue by MP. DOX + MP reduced loss of body weight. Oxidative stress was decreased, antioxidant activity was increased and histopathological changes were reduced in the DOX + MP group compared to the DOX group. Liver injury caused by DOX was attenuated by MP treatment owing to the antioxidative and anti-apoptotic effects of MP, which might be useful for reducing the severity of DOX induced liver injury.     

Hypoglycemic and hepatoprotective activity of Rosmarinus officinalis extract in diabetic rats

The present study examined the effect of water extract (200 mg/kg body weight) of Rosmarinus officinalis L. in streptozotocin (STZ)-induced diabetic rats for 21 days. The hepatoprotective effects were investigated in the liver tissues sections. There was a significant increase in serum liver biochemical parameters (aspartate aminotransferase, alanine transaminase, and alkaline phosphatase), accompanied by a significant decrease in the level of total protein and albumin in the STZ-induced rats when compared with that of the normal group. The high-dose treatment group (200 mg/kg body wt) significantly restored the elevated liver function enzymes near to normal. This study revealed that rosemary extracts exerted a hepatoprotective effect. The results indicate that the extract exhibits the protective effect on tissues and prove its potentials as an antidiabetic agent.     

Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative,Endoplasmic Reticulum Stress Cascade,and Neuroinflammation

Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.     

The Effect of Boron on Some Biochemical Parameters in Experimental Diabetic Rats

In this study, we evaluated the effect of boron (B) as boric acid (BA) on body weight (b.w.); blood glucose; plasma insulin; lipase and paraoxonase (PON1) activities; and serum triglyceride, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, lipid peroxidation (MDA), and total antioxidant capacity (TAC) in streptozotocin (STZ)-induced experimental diabetes in rats. Sixty Wistar albino rats (200–250 g) were divided into six groups of ten. The groups received the following treatment: group 1, control group; group 2, 50 mg/kg (b.w.) i.p. STZ-induced diabetes; group 3, 5 mg/kg (b.w.) B; group 4, 10 mg/kg (b.w.) B; group 5, diabetes + 5 mg/kg (b.w.) B; and group 6, diabetes + 10 mg/kg (b.w.) B. The experiment lasted 4 weeks. Increased serum MDA levels with diabetes were significantly reduced and although it is not statistically significant, serum TAC levels approached to values of control group; also, insignificant increases were observed in HDL cholesterol levels in experimental diabetic rats with treatment 5 and 10 mg/kg B. Furthermore, body weight, plasma insulin, and lipase activities increased insignificantly, blood glucose and serum LDL cholesterol decreased significantly, and total cholesterol levels decreased insignificantly in the diabetes + 10 mg/kg B group. There was no difference between the groups in terms of plasma PON1 activities and serum triglyceride levels. In conclusion, B may have beneficial effects on some biochemical parameters changes in experimental diabetes, and in order to determine the full effect of this element on the metabolism, further studies are required which use various dosages and compounds of B.     

Evaluation of Long-Term Toxicity of Oral Zinc Oxide Nanoparticles and Zinc Sulfate in Mice

The toxicological effects of zinc oxide nanoparticles (nano-ZnOs) are related to their dissolution and interference with zinc ion homeostasis. High-soluble zinc sources may produce more severe and acute toxicity; however, the evaluation of potential toxicity of long-term exposure to nano-ZnOs and high-soluble sources of zinc remains obscure. This study aimed at evaluating effects of nano-ZnOs and zinc sulfate on development, serum and hematological parameters, and mineral concentrations in selected tissues and intestinal microbiota in mice via gastrointestinal administration for 7 weeks. Results indicated that 250 mg/kg nano-ZnOs reduced the body weight from weeks 8 to 11, increased serum glutamic-pyruvic transaminase activity, and increased the zinc concentrations of the serum, liver, and kidney while did not affect the relative organ weight, intestinal microbiota, and other mineral concentrations (Fe, Cu, and Mn) in the kidney, liver, and thigh muscle. Oral administration with 250 mg/kg zinc sulfate seemed to show more severe and acute toxicity since mice in zinc sulfate group exhibited reduced body weight from weeks 5 to 11, decreased relative pancreas weight, and increased serum glutamic-oxalacetic transaminase activity and intestinal enteric group.     

Antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom, Pleurotus ostreatus, and its major constituent, chrysin, in Triton WR-1339-induced hypercholesterolemic rats

Hypercholesterolemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. In the present study, an attempt was made to evaluate the putative antihypercholesterolemic and antioxidative effects of an ethanolic extract of the oyster mushroom (Pleurotus ostreatus) and chrysin, one of its major components, in hypercholesterolemic rats. Hypercholesterolemia was induced in rats by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg body weight (b.wt.)), which resulted in persistently elevated blood/serum levels of glucose, lipid profile parameters (total cholesterol, triglycerides, low-density lipoprotein-, and very low-density lipoprotein-cholesterol), and of hepatic marker enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase). In addition, lowered mean activities of hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) and lowered mean levels of nonenzymatic antioxidants (reduced glutathione, vitamin C, and vitamin E) were observed. Oral administration of the mushroom extract (500 mg/kg b.wt.) and chrysin (200 mg/kg b.wt.) to hypercholesterolemic rats for 7 days resulted in a significant decrease in mean blood/serum levels of glucose, lipid profile parameters, and hepatic marker enzymes and a concomitant increase in enzymatic and nonenzymatic antioxidant parameters. The hypercholesterolemia-ameliorating effect was more pronounced in chrysin-treated rats than in extract-treated rats, being almost as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt.). These results suggest that chrysin, a major component of the oyster mushroom extract, may protect against the hypercholesterolemia and elevated serum hepatic marker enzyme levels induced in rats injected with Triton WR-1339.     

Influence of Different Amounts and Sources of Selenium Supplementation on Performance, Some Blood Parameters, and Nutrient Digestibility in Lambs

Two trials were conducted in a 2?×?2?+?1 factorial arrangement based on a completely randomized design to evaluate the effects of different sources of selenium (Se) on performance, blood metabolites, and nutrient digestibility in male lambs on a barley-based diet. The first trial lasted for 70 days and consisted of 30 lambs (35.6?±?2.6 kg mean body weight, about 4–5 months of age) which were randomly allotted to five treatments including: (1) basal diet (containing 0.06 mg Se/kg DM; control) without supplementary Se, (2) basal diet?+?0.20 mg/kg Se as sodium selenite (SeS 0.20), (3) basal diet?+?0.40 mg/kg Se as sodium selenite (SeS 0.40), (4) basal diet?+?0.20 mg/kg Se as selenium yeast (SeY 0.20), and (5) basal diet?+?0.40 mg/kg Se as selenium yeast (SeY 0.40). For the second trial, four lambs from each group of experiment 1 were randomly allocated to individual metabolic cages for 14 days to measure the effects of dietary Se on nutrient digestibility. The results revealed that there were no significant differences for average daily gain, average daily feed intake, feed/gain ratio, hematological parameters (packed cell volume, red blood cell, white blood cell, and hemoglobin values), serum total protein, albumin, globulin, aspartate amino transferase, alkaline phosphatase, and creatine phosphokinase due to supplementation of different amounts and sources of Se in lambs. Dietary Se supplementation significantly improved (P?<?0.001) glutathione peroxidase activity in blood. Furthermore, at the end of the trial, serum tri-iodothyronine (T3) amount also increased (P?<?0.05), while serum thyroxine (T4) amount decreased (P?<?0.05). Digestibility of dry matter, organic matter, crude protein, neutral detergent fiber, and acid detergent fiber increased (P?<?0.05) by Se yeast supplementation. It may be concluded that supplementation of Se in lambs had no significant effect on performance and blood hematology, but increased blood glutathione peroxidase activity and serum T3 amount and decreased serum T4 amount as compared to non-supplemented control lambs. Furthermore, Se yeast improved nutrient digestibility in lambs.     

Influence of resveratrol on liver fibrosis induced by dimethylnitrosamine in male rats

Liver fibrosis is a significant health problem which represents the liver’s scarring process and response to injury through deposition of collagen and extracellular matrix, and ultimately leads to cirrhosis. Resveratrol is a naturally occurring phytoalexin found predominantly in grapes. This study aimed to investigate the antifibrotic role of resveratrol on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Rats were divided into four groups and treated for three weeks; control, resveratrol administered orally (20 mg/kg daily), DMN intraperitoneally injected (10 mg/kg 3 days/week), and the last group was pre-treated daily with resveratrol then injected with DMN, 3 days/week. DMN administration induced severe liver pathological alterations. However, oral administration of resveratrol before DMN significantly prevented the induced loss in body weight, as well as the increase in liver weight which arise from DMN administration. Resveratrol has also inhibited the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin levels. Furthermore, resveratrol significantly increased hepatic reduced glutathione (GSH) levels and reduced the levels of malondialdehyde (MDA) due to its antioxidants effect as well as increased serum protein levels. In addition, DMN induced elevation in hydroxyproline content. On the other hand, hydroxyproline level was significantly reduced in the resveratrol pretreated rats. Resveratrol has also remarkably maintained the normal liver lobular architecture. Moreover, resveratrol had displayed potent potentials to prevent collagen deposition, lymphocytic infiltration, necrosis, steatosis, vascular damage, blood hypertention, cholangiocyte proliferation. It can be concluded that resveratrol has a marked protective role on DMN-induced liver fibrosis in rats, and can be considered as antiproliferative, antihypertensive, as well as antifibrotic agent and may be used to block the development of liver fibrosis.     

Therapeutic Potential of Some Plant Extracts Used in Turkish Traditional Medicine on Streptozocin-Induced Type 1 Diabetes Mellitus in Rats

Diabetes mellitus (DM) is known to impair many physiological functions. Some reports claim that medicinal plants can reduce these alterations caused by DM. The aim of this study was to investigate the therapeutic potential of aqueous-methanol extracts of Urtica dioica, Thymus vulgaris (TV), Myrtus communis (MC), Scolymus hispanicus (SH) and Cinnamomun zeylanicum (CZ) on streptozotocin (STZ)-induced type 1 DM in rats. Diabetes was induced via a single i.p. injection of STZ (65 mg/kg body weight). After 1 week to allow for development of diabetes, each plant extract was administered to diabetic rats separately at a dose of 100 mg/kg body weight daily for 28 days. The results showed that only SH extract significantly (P < 0.05) amended fasting blood glucose level. The lipid profile was ameliorated especially by supplementations of TV, MC and CZ extracts. Almost all plant extract treatments markedly (P < 0.05) increased reduced glutathione content and decreased lipid peroxidation levels of erythrocyte, plasma, retina and lens tissues. They also significantly (P < 0.05) amended erythrocyte catalase activity, levels of marker serum enzymes (except amylase), urea and blood urea nitrogen when compared to diabetic rats treated with nothing. Furthermore, none of the plant extracts counteracted body weight loss of diabetic rats. Our data revealed that the aforementioned plant extracts have remarkable potential to counteract DM-caused alterations, probably through their antioxidant and free radical-defusing effects.     

Preclinical Analgesic and Safety Evaluation of the GalR2-preferring Analog,NAX 810-2

The potential clinical utility of galanin peptidic analogs has been hindered by poor metabolic stability, lack of brain penetration, and hyperglycemia. In addition to possessing potent anticonvulsant efficacy, galanin analogs are analgesic in various assays. The purpose of these studies was to evaluate the lead galanin receptor type 2 (GalR2)-preferring analog, NAX 810-2, in various pain assays, as well as determine any potential for insulin inhibition, growth hormone stimulation, and cognitive impairment. NAX 810-2 was evaluated in mouse (carrageenan, formalin, tail flick, plantar incision) and rat pain models (partial sciatic nerve ligation). NAX 810-2 dose-dependently increased paw withdrawal latency following plantar administration of carrageenan (ED₅₀ 4.7 mg/kg). At a dose of 8 mg/kg, NAX 810-2 significantly attenuated nociceptive behaviors following plantar administration of formalin, and this was observed for both phase I (acute) and phase II (inflammatory) components of the formalin behavioral response. NAX-810-2 was active at higher doses in the mouse tail flick model (ED₅₀ 20.2 mg/kg) and similarly, reduced mechanical allodynia following plantar incision in mice at a dose of 24 mg/kg. NAX 810-2 also reduced mechanical allodynia in the partial sciatic nerve ligation model at a dose of 4 mg/kg. In addition, NAX 810-2 did not impair insulin secretion at doses of 2.5 and 8 mg/kg (acutely) or at a dose of 8 mg/kg given daily for 5 days. Similarly, 8 mg/kg (twice daily, 5 days) of NAX 810-2 did not increase growth hormone levels. These results demonstrate that NAX 810-2 possesses a favorable pre-clinical profile as a novel and first-in-class analgesic.