Gavage Technique Research Articles

Induction of Experimental Peri-Implantitis with Strains Selected from the Human Oral Microbiome.

Peri-implantitis (PI), the most widespread condition in the oral cavity, affects patients globally; thus, advanced research in both in vitro and in vivo studies is required. This study aimed to develop peri-implantitis in the rat model by oral contamination with bacteria responsible for PI in humans. The study was carried out in three stages: the extraction of the maxillary first molar to reproduce the human edentation, the mounting of the implant, and finally, the contamination of the device by gavage with Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Streptococcus oralis. The hematological examinations showed statistically significant increases for WBCs (white blood cells), Hb (hemoglobin), RBCs (red blood cells), MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration), and PLTs (platelets), but especially for the level of neutrophils and lymphocytes, and the systemic immunoinflammatory index completed the picture related to the inflammatory response triggered as a result of the activity of microorganisms pathogens on oral tissues. By examining the liver and kidney profile, we hypothesized that peri-implantitis is associated with systemic diseases, and the histopathological examination showed peri-implantitis lesions characterized by a marked inflammatory infiltrate with numerous neutrophils and lymphocytes. By corroborating all the results, we successfully developed a rat peri-implantitis model using a mixed bacterial infection through the oral gavage technique.

Effects of glutamine and omega-3 fatty acids on intestinal neomucosa formation on colon serosa in rats.

Intestinal neomucosa formation is a technique defined for the treatment of short bowel syndrome. This study evaluates the effect of glutamine and omega-3 fatty acids on the growth of intestinal neomucosa on the colonic serosal surface has been evaluated. Thirty-two adult male Sprague-Dawley rats were randomly divided into 4 groups: sham, control, glutamine, and omega-3. Laparotomy was performed on all groups. For rats other than the sham group, a 1-cm full-thickness incision was made 4 cm proximal to the ileocecal valve, and colonic serosal surface was sutured as a serosal patch over these openings. By using the oral gavage technique, the glutamine group was ingested with 200 mg/kg/day of glutamine, and the omega-3 group was ingested with 100 mg/kg/day of omega-3 fatty acids. At the end of 14 days, the rats were euthanized, blood specimens were collected, and intestinal segments, including serosal patches, were excised. Transforming growth factor-beta was significantly lower in the glutamine group compared to the control group. Similarly, fibroblast growth factor-2 was significantly lower in the glutamine group compared to the sham group. Intestinal neomucosa formation was observed in 100% of rats in the glutamine group. In the control and omega-3 groups, intestinal neomucosa formation was observed in 57.1% and 60% of rats, respectively. The inflammatory response, granulation tissue formation, and fibroblastic activity were more severe in the rats of the glutamine and omega-3 groups. The intestinal neomucosa formation is an experimental technique, and both glutamine and omega-3 fatty acids have the potential to positively affect inflammatory response, granulation tissue formation, and fibroblastic activity. Specifically, glutamine has a favorable effect on intestinal neomucosa formation.

Copaifera langsdorffii Desf. tree oleoresin-induced antinociception recruits µ1- and κ -opioid receptors in the ventrolateral columns of the periaqueductal gray matter

Popular medicine has been using oleoresin from several species of copaíba tree for the treatment of various diseases and its clinical administration potentially causes antinociception. Electrical stimulation of ventrolateral (vlPAG) and dorsolateral (dlPAG) columns of the periaqueductal gray matter also causes antinociception. The aim this study was to verify the antinociceptive effect of oleoresin extracted from Copaifera langsdorffii tree and to test the hypothesis that oleoresin-induced antinociception is mediated by µ1- and κ-opioid receptors in the vlPAG and dlPAG. Nociceptive thresholds were determined by the tail-flick test in Wistar rats. The copaíba tree oleoresin was administered at different doses (50, 100 and 200 mg/kg) through the gavage technique. After the specification of the most effective dose of copaíba tree oleoresin (200 mg/kg), rats were pretreated with either the µ1-opioid receptor selective antagonist naloxonazine (at 0.05, 0.5 and 5 µg/ 0.2 µl in vlPAG, and 5 µg/ 0.2 µl in dlPAG) or the κ-opioid receptor selective antagonist nor-binaltorphimine (at 1, 3 and 9 nmol/ 0.2 µl in vlPAG, and 9 nmol/ 0.2 µl in dlPAG). The blockade of µ1 and κ opioid receptors of vlPAG decreased the antinociception produced by copaíba tree oleoresin. However, the blockade of these receptors in dlPAG did not alter copaíba tree oleoresin-induced antinociception. These data suggest that vlPAG µ1 and κ opioid receptors are critically recruited in the antinociceptive effect produced by oleoresin extracted from Copaifera langsdorffii.

A Novel Probiotic Combination Ameliorates Crohn's Disease-Like Ileitis by Increasing Short-Chain Fatty Acid Production and Modulating Essential Adaptive Immune Pathways.

Crohn's disease (CD) represents a significant public health challenge. We identified a combination of beneficial probiotic strains (Saccharomyces boulardii, Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium breve) and amylase that may antagonize elevated bacterial pathogens in the inflamed gut. Our aim was to characterize the effect(s) of this novel probiotic supplement in SAMP1/YitFc (SAMP) mice with CD-like ileitis. Three groups of 7-week-old SAMP mice were used in this study. The first experimental group was administered 1 dose of the probiotic supplement (probiotic strains + amylase) diluted in sterile phosphate-buffered saline (PBS) (0.25 mg in 100 µL of PBS) every day for 56 days through the gavage technique, the second group had a probiotic supplement (probiotic strains without amylase), and the third group was a control group in which animals were administered sterile PBS. At the end of the treatment, mice were sacrificed and ilea were collected for histological scoring of ileitis and NanoString analysis. Stool samples were evaluated by 16S ribosomal RNA and gas chromatography-mass spectrometry analyses. Histology scores showed that mice treated with probiotics + amylase had a significant decrease of ileitis severity compared with the other 2 groups. 16S ribosomal RNA and gas chromatography-mass spectrometry analysis showed that abundance of species belonging to genus Lachnoclostridium and Mucispirillum schaedleri were significantly increased compared with the other 2 groups, and this increase was associated with augmented production of short-chain fatty acids. NanoString data showed that 21 genes involved in B memory cell development and T cell infiltration were significantly upregulated in probiotic-treated mice and that 3 genes were significantly downregulated. Our data provide experimental proof for a beneficial effect of the designed probiotic formulation on the severity of CD-like ileitis in the SAMP mouse model, involving both alteration of intestinal genetic pathways and microbial rearrangements. Thus, we propose that this novel probiotic mixture should be further tested as an adjuvant therapy in the treatment of biofilm-associated disorders such as CD, in which it has been proven that polymicrobial imbalance plays a critical role in dysbiosis and gut inflammation.

Melissa Officinalis L. aqueous extract pretreatment decreases methotrexate-induced hepatotoxicity at lower dose and increases 99mTc-phytate liver uptake, as a probe of liver toxicity assessment, in rats.

Hepatotoxicity remains amongst the restricting factors of Methotrexate (MTX)-associated cancer therapy, especially in high doses of chemo-drugs or prolonged treatment. Due to the known protective effects ofMelissa officinalis(M. officinalis), the aqueous extract of this plant was evaluated to ameliorate MTX-associated hepatotoxicity in rats. Adult female Wistar rats were received or notM. officinalisaqueous extract at doses of 100mg/kg (for 14 and 24 consecutive days) and 2g/kg (for 14 consecutive days) by gavage technique. MTX (20mg/kg) was intraperitoneally injected on the 10th- and 20th-day post-M.officinalistreatment. 24h after the last day of treatment, 99mTc-phytate was intravenously injected through the tail of rats. Animals were killed at 20min after radiocolloid injection, and vital tissues including the liver and spleen were isolated, weighed, and their radioactivity was counted. As well, 99mTc-phytate scintigraphy and histopathology of the liver were performed for higher accuracy. A significant increase in liver radioactivity was detected inM. officinalis+MTX receiving groups compared with the MTX rats which were more robust at a dose of 100mg/kg for 14days. Also, a significant reduction in liver radioactivity was evident withM. officinalisextract at a dose of 2g/kg for 14days in comparison with the control group, this reduction was not significant at the lower dose of 100mg/kg. Gamma scintigraphy and histopathological examinations confirmed the hepatoprotective effect ofM. officinalisvs MTX-induced liver injury in rats. In conclusion, we highlighted the liver uptake of 99mTc-phytate as a valuable method for assessment of liver toxicity and addressed that M. officinalis pretreatment (100mg/kg for 14days) ameliorates the MTX-associated hepatotoxicity in rats; however, M. officinalis itself induces liver toxicity at higher doses.

The Protective Effects of S-Methyl Methionine Sulfonium Chloride on Brain Tissue Damage in D-Galactosamine-Induced Hepatotoxicity

Objective: The objective of the current work is to examine the protective effects of S-methyl methionine sulfonium chloride (MMSC) on brain in galactosamine (GalN)-induced hepatotoxicity in rats. Materials and Methods: A total of twenty two female Sprague-Dawley rats were randomly assigned into four groups as follows: Group I (n=5), intact control animals; Group II (n=6), animals that received 50 mg/kg/day of MMSC by gavage technique for 3 consecutive days; Group III (n=5), animals injected with a single dose of 500 mg/kg of GalN intraperitoneally (i.p.); and Group IV (n=6) are animals injected with the same dose of GalN (i.p.) 1 hour after MMSC treatment. At the end of the experiments (after 6 hours of the last GalN treatment), all animals were sacrificed under anaesthesia, and brain tissues were dissected out. Results: A statistically remarkable increase in lipid peroxidation, hydroxyproline, and nitric oxide levels, was detected while a notable decline in the activities of sodium/potassium ATPase was observed in GalN group in comparison with control rats. In contrast, all alterations observed were reversed when MMSC was given to GalN groups. Conclusion: Consequently, it may be considered that MMSC has a protective role on brain in GalN-induced hepatotoxicity in rats.

Oxidative brain and cerebellum injury induced by d-galactosamine: Protective effect of S-methyl methionine sulfonium chloride.

The objective of this study was to examine the protective effects of S-methyl methionine sulfonium chloride (MMSC) against galactosamine (GalN)-induced brain and cerebellum injury in rats. A total of 22 female Sprague-Dawley rats were randomly divided into four groups as follows: Group I (n = 5), intact animals; Group II (n = 6), animals received 50 mg/kg/day of MMSC by gavage technique for 3 consecutive days; Group III (n = 5), animals injected with a single dose of 500 mg/kg of GalN intraperitoneally (ip); and Group IV (n = 6), animals injected with the same dose of GalN 1 h after MMSC treatment. After 6 h of the last GalN treatment (at the end of the experiments), all animals were killed under anesthesia, brain and cerebellum tissues were dissected out. Reduced glutathione, total antioxidant status levels, and antioxidant enzymes (catalase, superoxide dismutase, and glutathione-related enzymes), aryl esterase, and carbonic anhydrase activities remarkably declined whereas advanced oxidized protein products, reactive oxygen species, total oxidant status, oxidative stress index levels, and myeloperoxidase, acetylcholinesterase, lactate dehydrogenase, and xanthine oxidase activities were significantly elevated in the GalN group compared with intact rats. In contrast, the administration of MMSC to GalN groups reversed these alterations. In conclusion, we may suggest that MMSC has protective effects against GalN-induced brain and cerebellar toxicity in rats.

Impact of oral gavage technique of drug-containing microcontainers on the gastrointestinal transit and absorption in rats

Oral gavage is the most common way to administer drug formulations orally to rats. Yet, the technique applied and its influence on gastrointestinal (GI) transit receive little attention. This study aims to investigate the impact of three oral gavage techniques on GI transit and drug absorption utilizing microcontainers (MCs). The MCs were filled with paracetamol and BaSO4 (1:1 w/w ratio), coated with Eudragit S100, and filled into size-9 gelatin capsules. An in vitro study confirmed the intactness of the coating, and the capsules were administered to rats with air, water, or a piston. X-ray imaging determined the locations of the MCs, and the corresponding plasma concentration of paracetamol established a correlation with the location. The fastest GI transit occurred with air-dosing, while water-dosing caused delayed gastric emptying for 3 h with non-quantifiable paracetamol absorption. Piston-dosed MCs were retained in the stomach for up to 1 h, though for 3 h in one rat. Air-dosing caused discomfort and stress in rats, thus limiting its ethical and physiological relevance. Water-dosing confined its use due to delayed gastric emptying. In conclusion, the oral gavage technique affected the GI transit of MCs and, consequently, drug absorption. Piston-dosing appeared to be the superior dosing technique.

Investigating the impact of silymarin on liver oxidative injury.

Introduction:Various drugs affect liver problems caused by general hypoxia, including silymarin. Due to the fungal killer toxins, nowadays, silymarin (milk thistle) is used as an effective drug in the prevention and treatment of liver diseases and liver toxicity. In addition, silymarin protects the liver cells from solvents and chemical substances. The aim of this paper is to investigate the impact of silymarin on liver problems induced by general hypoxia.Material and Methods:This study was a double-blinded clinical trial on patients with hypoxia who referred to the hospital emergency department. Patients were randomly divided into case and control groups. The case group was treated with silymarin at a dose of 280 mg with orally gavage technique and the control group was treated with a placebo every 8 h for 3 days. To investigate the leukocytosis, liver enzymes levels of alanine transaminase (ALT), aspartate aminotransferase (AST), creatine phosphokinase (CPK), prothrombin time (PT), partial thromboplastin (PTT), international normalized ratio (INR), and white blood cell (WBC) were measured before and after the intervention. SPSS 21 software was used to analyze the data.Results:In the silymarin group, liver enzymes were lower than the placebo group on the third day after treatment (P < 0.05). There was no significant difference between the two groups in terms of coagulation factors and WBC count on the third day after treatment (P > 050). On the third day after treatment, the amount of GGT was lower in the silymarin group (P < 0.05).Conclusion:Silymarin decreased liver enzymes (ALT, AST, and CPK) and the level of GGT. Therefore, it is recommended to be used in patients with hypoxic liver injury.

The effects of vitamins and selenium mixture against brain tissue induced by d-galactosamine.

Brain damage is a major complication of fulminant hepatic failure. d-Galactosamine (d-GalN)-induced liver toxicity causes damage to brain. The effects of vitamins and selenium mixture against d-GalN stimulated brain injury were investigated in this study. Sprague-Dawley female rats aged 2.0-2.5 months were used for the study. The rats were divided into four categories. A 0.9% NaCl solution was intraperitoneally given to the experimental rats in the first group. Using gavage technique, the second group of animals were subjected to a formulation consisting of 100 mg·kg-1 ·day-1 vitamin C, 15 mg·kg-1 ·day-1 of β-carotene, 100 mg·kg-1 ·day-1 of α-tocopherol in addition to 0.2 mg·kg-1 ·day-1 of sodium selenate for 3 days. The third group was given a single dose of d-GalN hydrochloride at the concentration of 500 mg·kg-1 through a saline injection. The final group was given similar concentrations of both the antioxidant combination and d-GalN. Tissue samples were collected under ether anesthesia. The rats treated with d-GalN showed brain damage; increased myeloperoxidase, catalase, glutathione peroxidase, glutathione-S-transferase, lactate dehydrogenase, and superoxide dismutase activities; and decreased glutathione levels. Treatment with vitamins and selenium combination resulted in alleviation of these alterations in the rats. These findings suggest that administration of the vitamins and selenium combination suppresses oxidative stress and protects brain cells from injury induced by d-GalN.

Beneficial effects of aqueous extracts of Mikania glomerata Sprengel and Mikania laevigata Schultz Bip ex Baker on the inflammatory response in rats with acute pancreatitis

ObjectivesAccording to previous studies, aqueous extracts of Mikania glomerata (MG) and Mikania laevigata (ML) possess considerable anti‐inflammatory activity. Altogether, these findings suggest that these species has a potential effect in the treatment of inflammatory conditions, particularly those involving the gastrointestinal tract. In view of this, it is believed that these species may present important effects in the treatment of acute pancreatitis. Since there is no specific pharmacological therapy for acute pancreatitis, the elucidation of this parameter is the main objective of this study, in an attempt to prove the therapeutic efficacy of these plants under this condition.Material and MethodsThe extracts were characterized by Ultra High Efficiency Liquid Chromatography coupled to Mass Spectrometry (UHPLC‐MS). The animals were treated per oral route (p.o.), through the gavage technique, in the final volume of 500 μL, for 7 consecutive days and then submitted to induction of acute pancreatitis (AP). Male Wistar rats were submitted to injection of sodium tauracholate (30 mg/kg) into the common bile duct. After 4 hours the animals were sacrificed, when blood, pancreas and left lung were collected for analysis of pancreatic edema, pancreatic and pulmonary neutrophil infiltrate (MPO), elevation of serum amylase, TNF‐α in serum and interleukins.Results and DiscussionInduction of AP by sodium tauracholate significantly increased all the parameters evaluated when compared with the respective sham group. The pretreatment with MG (400 mg/kg) significantly reduced pancreatic oedema, pancreas and lung MPO activity. The same profile of reduction was observed in the pretreatment with coumarin (75 mg/kg). The pretreatment with ML showed a significant reduction for all doses tested in the pancreatic oedema and lung MPO activity. For pancreas MPO activity, the doses of 200 and 400 mg/kg showed significant reduction of this parameter.ConclusionOur results showed that aqueous extracts of M. glomerata and M. laevigata decreases inflammation acute pancreatitis, making it of interest in future approaches to treat this condition. However, additional studies are being made by our group to establish the effectiveness of this mechanism.Support or Funding InformationCamila S. P. Della Pasqua is a fellowship of National Council for Scientific and Technological Development (CNPQ).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Histoprotective potentials of ethanol leaf extract of balakat tree (Ziziphus talanai (blanco) merr.) against tetracycline-induced hepatotoxicity and reprotoxicity in male mice (Mus musculus L.)

Hepatic dysfunction can develop due to ROS and lipid peroxide and may lead to primary liver cancer. Hepatic dysfunction may also develop from tetracycline, an antibiotic with a broad-spectrum of bacteriostatic mechanisms, as it can induce hepatotoxicity and reprotoxicity. In addition, liver tumors secrete hormones that can result to testicular atrophy. Thus, there is a need to address liver and testicular damage. Preliminary phytochemical analysis indicated the presence of bioactive compounds with histoprotective potentials in Balakat tree (Ziziphus talanai), which is used in Antique against urinary tract infection. Twelve male mice were divided into four groups of three mice each. Treatments were administered via intragastric gavage technique for 30 days. T0 is the negative control group treated only with water at a dose level of 0.5 ml/20 g body weight (bw). T+ is the positive control group treated only with tetracycline at a dosage level of 0.5ml/20 g bw. T1 and T2 received 0.3 ml/20 g bw and 0.5 ml/20 g bw Z. talanai ethanol leaf extract, respectively.Histopathological evaluation revealed that T+ mice showed hepatotoxicity based on central vein rupture, fibrosis, vacuolations, cytoplasmic degeneration, lymphocyte infiltration, small amount of glycogen deposits and fibrous septa. Reprotoxicity was also observed as indicated by formation of irregularly shaped tubules, narrowing of tubule diameter, widening of the lumen, germinal epithelium exfoliation, reduction in tubules’ cross-sectional areas, absence of germ cell bundles and blood-testis barrier destruction. T1 and T2 mice showed normal liver and seminiferous tubule architectural design as compared to those of T+ mice. Thus, the Z. talanai leaf extract mitigated the hepatotoxicity and reprotoxicity effects of tetracycline causing an improvement in the hepatological and testicular parameters. The ethanolic leaf extract of Z. talanai (Blanco) Merr. Contains bioactive compounds with histoprotective potentials.

Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies.

ABSTRACTZebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAFV600E inhibitor, Vemurafenib, in adult zebrafish harboring BRAFV600E melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases.

Black tea extract improves anti-oxidant profile in experimental diabetic rats

Objective: The purpose of this study was to investigate the in vivo anti-oxidant effect of black tea extract (BTE) supplemented to normal and alloxan-induced diabetic rats. Methods: Black tea extract (BTE) was fed to control and experimental diabetic rats by gavage technique at a dose of 1 ml/100 g body weight/day. Markers of oxidative stress in blood were determined. Result: Results show a significant (P < 0.01) decrease (73%) in plasma anti-oxidant potential, increase in activity of plasma membrane redox system (122%), protein oxidation and lipid peroxidation in diabetic rats, BTE supplemented diabetic rats had improved anti-oxidant profile and lower protein and lipid peroxidation levels. Diabetic rats displayed lower intracellular glutathione (GSH), BTE supplementation improved GSH levels. Conclusion: Results of this study suggest that the 2.5% aqueous extract of black tea is effective to ameliorate diabetes associated oxidative stress parameters in experimental model of diabetes.

Histopathological and ultra structural effects of nanoparticles on rat testis following 90days (Chronic study) of repeated oral administration.

BackgroundNanoparticles (Ag NPs) have recently received much attention for their possible applications in biotechnology and biomedical. However, little is known about the toxicity in reproductive organs of animal model following exposure to nanoparticles.ObjectiveThis study therefore, tried to examine the effects of nanoparticles with a diameter range of 5-20 nm on the histology of the testis of wistar rats and correlate it with Transmission Electron Microscopy results.Materials and methodsSixteen wistar rats were randomly divided into two groups of 8 rats each. Each group received the following via gavage technique for 90 days: Control Group (Group-1)-tap water; Experimental group (Group 2) - nanoparticles (20ug/kg/day). After ninety days (chronic study), rats were sacrificed and testis tissues was processed for histology and transmission electron microscopic study.ResultsThere was significant difference between the observations of group-1 and group 2. The changes observed in the testis were disarray of the spermatogenic cells and disorientation of the testis. These changes were observed to have been disappearing from normal histological features. Detailed structural damages were observed with TEM analysis, such as depletion of germ cells, germinal cells necrosis, especially in spermatogonia and Leydig cells had an abnormal fibroblast-like appearance, abnormal space between neighboring sertoli cells, mitochondria, lost cristae and vacuolated (none energized) with those animals exposed to nanoparticles.ConclusionIt seems that nanoparticles have acute and significant effects on spermatogenesis and number of spermatogenic cells. More experimental investigations are necessary to elucidate better conclusion regarding the safety of nanoparticles on male reproduction system.

Protective effect of vanadyl sulfate on skin injury in streptozotocin-induced diabetic rats

The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the skin tissues of diabetic and control rats. In this study, 6-6.5 months old male Swiss albino rats were used. The animals were randomly divided into the following four groups: group I, control (nondiabetic intact animals); group II, vanadyl sulfate control; group III, streptozotocin (STZ)-diabetic animals and group IV, STZ-diabetic animals given vanadyl sulfate. The animals were made diabetic by intraperitoneal injection of a single dose of 65mg/kg STZ in 0.01M citrate buffer (pH=4.5). From day 1 to day 60, 100mg/kg vanadyl sulfate was given daily by gavage technique to one of the control and diabetic groups. Body weights and blood glucose levels were estimated on experimental days 0, 1 and 60. On the 60th day, skin tissue samples were taken, glutathione (GSH), lipid peroxidation (LPO), nonenzymatic glycosylation (NEG) and protein levels, catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were determined. Blood glucose, skin LPO and NEG levels increased, but skin GSH levels and CAT, SOD and GST activities decreased in the STZ group. Treatment with vanadyl sulfate reversed these effects. The present study showed that vanadyl sulfate exerted antioxidant properties and may prevent skin damage caused by diabetes.

Protective effect of vanadyl sulfate on skin injury in streptozotocin-induced diabetic rats.

The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the skin tissues of diabetic and control rats. In this study, 6-6.5 months old male Swiss albino rats were used. The animals were randomly divided into the following four groups: group I, control (nondiabetic intact animals); group II, vanadyl sulfate control; group III, streptozotocin (STZ)-diabetic animals and group IV, STZ-diabetic animals given vanadyl sulfate. The animals were made diabetic by intraperitoneal injection of a single dose of 65mg/kg STZ in 0.01M citrate buffer (pH=4.5). From day 1 to day 60, 100mg/kg vanadyl sulfate was given daily by gavage technique to one of the control and diabetic groups. Body weights and blood glucose levels were estimated on experimental days 0, 1 and 60. On the 60th day, skin tissue samples were taken, glutathione (GSH), lipid peroxidation (LPO), nonenzymatic glycosylation (NEG) and protein levels, catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were determined. Blood glucose, skin LPO and NEG levels increased, but skin GSH levels and CAT, SOD and GST activities decreased in the STZ group. Treatment with vanadyl sulfate reversed these effects. The present study showed that vanadyl sulfate exerted antioxidant properties and may prevent skin damage caused by diabetes.

Effect of simultaneous blockade of androgen and estrogen receptors on prostate cancer: In vivo study.

214 Background: In our preliminary in vitro studies, we have demonstrated evidence of enhanced apoptosis and inhibition of cellular proliferation in both hormone sensitive and castrate resistant prostate cancer (PCa) cell lines using a combination of an antiandrogen (Bicalutamide) and a selective estrogen receptor modulator (Raloxifene). The aim of this study was to study the effect of the administration of these two drugs in in vivo models of castrate resistant PCa. Methods: In vivo model consisted on NCr Nude: Mice bearing s.c. human prostate (PC3 cell line) xenografts. Based on the treatment received, mice were divided into 5 groups as follows: Group 1: No drugs (control); Group 2: Bicalutamide 50mg; Group 3: Raloxifene 60 mg; Group 4: Combined administration of Bicalutamide 50 mg and Raloxifene 60 mg; Group 5 Combined administration of Bicalutamide 150 mg and Raloxifene 120 mg. A total of 10 mice where included in each group. All drugs dosages were converted to their equivalent in the mice. Drugs were administered by gavage technique to the mice once per day for a total of 14 days. Results: As expected, Bicalutamide administered alone causes minimal inhibition without reaching statistical significance (Group 2: 0.34 g Vs Group 1: 0.40 g; p=0.073). Although Raloxifene causes some marked growth inhibition, its effect is not statistically significant (Group 3: 0.31 Vs Group 1: 0.40 g; p=0.062). Bicalutamide and Raloxifene, when administered in combination, induced prominent growth inhibition in PC3 tumors when compared to the control group (Group 4: 0.26 g Vs Group 1: 0.40 g; p=0.038). Growth inhibition is significantly more evident when the drugs dosages are increased (Group 5: 0.17 g Vs Group 1: 0.40 g; p=0.024). Conclusions: The simultaneous administration of Bicalutamide and Raloxifene appears to have a synergistic effect on tumor growth inhibition in PC3 xenografts. The pathway(s) responsible for this observation may be independent of the androgen receptor as PC3 cells are AR negative and still affected by the combination over the drugs administered alone. Research is warranted to identify these potential pathways.

Combined effects of treatment with vitamin C, vitamin E and selenium on the skin of diabetic rats

The aim of this study was to investigate the effects of vitamin C, vitamin E and selenium (Se) on the skin tissue of streptozotocin-induced diabetic rats. Swiss albino rats were divided into four groups: control, control + antioxidants, diabetic, diabetic + antioxidants groups. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin. Vitamin C (250 mg/kg), vitamin E (250 mg/kg) and Se (0.2 mg/kg) were given by gavage technique to rats of one diabetic and one control group for 30 days. In the diabetic group, the levels of serum urea and creatinine, skin lipid peroxidation and nonenzymatic glycosylation levels increased, but skin glutathione levels decreased. Treatment with vitamin C, vitamin E and Se reversed these effects. The present study showed that vitamin C, vitamin E and Se exerted antioxidant effects and consequently may prevent skin damage caused by streptozotocin-induced diabetes.

Oral immunization of the African clawed frog (Xenopus laevis) upregulates the mucosal immunoglobulin IgX

The frog Xenopus laevis is a model species for developmental biology but is also of significant interest to comparative immunologists. Amphibians are the oldest group of organisms in which both the B lymphocytes of some species undergo immunoglobulin (Ig) class switch recombination and also have a dedicated mucosal Ig isotype. The purpose of this study was to test the hypothesis that frog IgX would be produced in response to oral immunization. In order to facilitate studies of humoral, and especially mucosal immunity, in this model species, we developed a gavage technique for oral immunization. The result of this oral administration of antigen to frogs was assayed by the induction of the mucosal antibody isotype, IgX, in plasma by enzyme linked immunosorbant assay (ELISA), and a significant IgX upregulation was detected compared to frogs receiving systemic immunization into the coelom. These data are consistent with the view that IgX is the functional analog of mammalian IgA and mandate further studies of the relationship between IgX and IgA. Additionally, the gavage technique should be adaptable for functional studies of gut-associated immunology in other small aquatic vertebrates.