Oral Gavage Method Research Articles

Evaluation of Immediate Release Tri-Layer Tablets for Analgesic and Antiulcer Properties in Experimental Animals.

Using animals as a test subject, we aimed to determine whether tri-layer tablets filled with ibuprofen and ranitidine had any effect on pain or ulcers. The effectiveness against ulcers caused by acetic acid and cold stress was tested. Six rats made up each of the four groups that were randomly assigned. As a control, I was given a solvent and placed in the group. The second group served as the control, while groups III and IV were used to evaluate 100 mg and 200 mg tri-layer tablets, respectively. The oral gavage method was used to administer all medications. It was shown that the number of writhing was 5.12 in the T2 group compared to the control group, indicating a decrease in the medication-treated groups. The heated technique demonstrated the substantial analgesic activity of the medication under examination. After 120 minutes, the drug-treated groups had a latency time that was 9.8 seconds longer than the control group. Treatment with the experimental medicine lowered the ulcer index in an ulcer model generated by acetic acid. T2 had a value that was 0.43 lower than the control group. T2 group showed a significant reduction in ulcer index to 0.33 in ulcers generated by cold restraint stress. This study provides support for the use of multilayered tablets in the treatment of pain and ulcer disorders, since it demonstrated the analgesic and antiulcer benefits of the test medicine in animal models. More studies to determine the exact mechanism are necessary.

Endosulfan induces reproductive & genotoxic effect in male and female Swiss albino mice

BackgroundToxicity by pesticide has become a global health issue and leaves a harmful impact on human health via various ways. The people exposed to pesticides in the rural population get affected by the harmful effects of it as they enter the human body system through skin, inhalation, oral administration, food chain and many more ways. The present work is designed to study the toxic effect of endosulfan in male (n=30) and female (n=30) Swiss albino mice. Endosulfan was administered by oral gavage (oral administration) method, at the dose of 3.5 mg/Kg body weight daily for period of 3 weeks, 5 weeks and 7 weeks. After the completion of the treatment, the mice were sacrificed and their ovary and testis tissues were dissected out to check the degeneration. The blood was collected for karyotyping, biochemical and hormonal analysis of pesticide induced genotoxicity. After 7 weeks of administration with Endosulfan, various abnormalities were observed in male and female mice.ResultsTreatment with endosulfan at the dose of 3.5 mg/Kg body weight caused a higher degree of degeneration in the reproductive organ of Swiss albino mice . Treatment by this pesticide generated degeneration in long duration of dosage for 3,5 and 7 weeks. Ovaries of endosulfan administered groups showed degenerated germinal epithelium, Graffian follicles and corpus luteum. In testis of endosulfan treated mice, microscopic examination showed that there is significant damage and reduction in the tissue of seminiferous tubules and primordial germ cells. High degree of degeneration caused the disarrangement and deformation of spermatogonia with the decrease in the number of Sertoli cells. Biochemical and hormonal properties was also affected by endosulfan treatment. There was significant 5 folds decrease in the testosterone value of endosulfan in 7 weeks treated mice in comparison to control (p < 0.0001) and similarly there was significant elevation in the estrogen levels found in 7th week endosulfan treated mice. It also influenced the level of free radicals as there was significant decrease (p < 0.0001) in the value in catalase levels in 7 weeks endosulfan treated male and female mice, while significant (p < 0.0001) increase in the values of lipid peroxidation levels as 8 folds and 10 folds in 7 weeks endosulfan treated male and female Swiss albino mice respectively. This study hence speculates that the endosulfan exposed population are at the risk of reproductive health hazards.ConclusionsThe present study thus concludes that, endosulfan after 7 weeks of exposure caused significant reproductive damage to both male and female Swiss albino mice groups. Moreover, the karyotyping study also correlated the genotoxic damage in the mice.

Assessing the Impact of Onion Juice on the Levels of Leutinizing Hormone and Follicle Stimulating Hormone in Female Mice Exposed to Transfluthrin Smoke

Assessing the Impact of Onion Juice on the Levels of Leutinizing Hormone and Follicle Stimulating Hormone in Female Mice Exposed to Transfluthrin Smoke

Carvacrol showed a curative effect on reproductive toxicity caused by Bisphenol AF via antioxidant, anti-inflammatory and anti-apoptotic properties

Bisphenol AF (BPAF) is an endocrine disruptor, and human exposure to these chemicals is growing in industrialized nations. BPAF has been demonstrated in studies to have toxic effects on reproductive health. This study examined the effects of oral exposure to BPAF on the reproductive system and the protective effects of carvacrol in rats. From 32 Wistar albino rats, four separate groups were set up for this purpose. Carvacrol 75 mg/kg and BPAF 200 mg/kg were administered by oral gavage method. Rat sperm parameters and serum testosterone levels were measured after 28 days of administration. The study looked at the MDA in the testis tissues, as well as CAT, GPx, and GSH as antioxidants parameters, NF-κB and TNF-α as inflammatory markers, caspase-3 and Bcl-2 as apoptosis parameters, and PCNA as cell proliferation markers. In addition, testis tissues underwent histological evaluation. As a result, in rats exposed to only BPAF, sperm counts declined, testosterone levels reduced, oxidative stress, inflammation, and apoptosis increased, and cell proliferation decreased. Furthermore, severe disruptions in tissue architecture and decreased spermatogenesis were reported. In contrast, sperm parameters improved, testosterone levels increased, oxidative stress and inflammation decreased, and apoptosis was prevented in the carvacrol-treated group compared to the BPAF-only group. It was also found that spermatogenesis was maintained, and structural abnormalities in testicular tissue were mostly avoided with an increase in PCNA expression. According to the findings, despite BPAF-induced testicular and reproductive toxicity, carvacrol had therapeutic potential due to its anti-inflammatory, antioxidant, cell proliferation-increasing, and anti-apoptotic activities.

The Effect of Vitamin E Supplement on Creatine Kinase MB, C-Reactive Protein, Creatinine and Urea Levels of Albino Rats Fed with High Fat Diet

Aim: This study was designed to assess the effect of vitamin E supplement on Creatine Kinase (CK-MB) C - reactive protein, (C-RP), urea and creatinine of albino rats fed with high fat diet.&#x0D; Methodology: A total of twenty (20) albino rats of both sexes were used in this study. They were grouped into four (4) groups comprising of five (5) rats each. Group 1 was fed with normal diet; group 2 with normal diet and treated with vitamin E supplement (70 mg/kg); group 3 was fed with high fat diet only, while group 4 was fed with high fat diet and treated with vitamin E supplement (70 mg/kg). The treatments were administered daily using oral gavage method for a period 21 days. After the experimental period, the animals were sacrificed and blood samples collected for the analysis of CK-MB, CRP, urea and creatinine respectively using ELISA and colorimetric method with a spectrophotometer. Data generated were analyzed statistically using SPSS version 20 and P = 0.05 was considered statistically significant.&#x0D; Results: The results revealed a significance difference in C-RP (mg/l) levels (P &lt; 0.001) amongst the groups with a decreased C-RP levels in group 2 (1.43 ± 0.39) compared to group 1 (1.94 ± 0.53), then in group 4 (2.27 ± 0.53) which is also decreased compared to group 3 (3.31 ± 0.63). For CK-MB there was also a significant difference among the different groups. In group 2, it was 1.94 ± 0.65 ng/ml which was decreased compared to group 1 (2.22 ± 0.55), and group 4 (2.74 ± 0.68) compared to group 3 (3.31 ± 0.62). For the urea and creatinine results, there was no significant difference (p &gt; 0.05) among the groups when the mean levels were compared.&#x0D; Conclusion: This shows that administration of vitamin E to rats fed normal or high fat diet could significantly reduce the plasma levels of CRP and CK-MB hence having some ameliorative effects on high fat induced inflammatory and cardiovascular risks or conditions.

Behavioral, Neurochemical and Developmental Effects of Chronic Oral Methylphenidate: A Review.

The majority of animal studies on methylphenidate (MP) use intraperitoneal (IP) injections, subcutaneous (SC) injections, or the oral gavage route of administration. While all these methods allow for delivery of MP, it is the oral route that is clinically relevant. IP injections commonly deliver an immediate and maximum dose of MP due to their quick absorption. This quick-localized effect can give timely results but will only display a small window of the psychostimulant's effects on the animal model. On the opposite side of the spectrum, a SC injection does not accurately represent the pathophysiology of an oral exposure because the metabolic rate of the drug would be much slower. The oral-gavage method, while providing an oral route, possesses some adverse effects such as potential animal injury and can be stressful to the animal compared to voluntary drinking. It is thus important to allow the animal to have free consumption of MP, and drinking it to more accurately mirror human treatment. The use of a two-bottle drinking method allows for this. Rodents typically have a faster metabolism than humans, which means this needs to be considered when administering MP orally while reaching target pharmacokinetic levels in plasma. With this oral two-bottle approach, the pathophysiological effects of MP on development, behavior, neurochemistry and brain function can be studied. The present review summarizes these effects of oral MP which have important implications in medicine.

Pollen and bee bread expressed highest anti-inflammatory activities among bee products in chronic inflammation: an experimental study with cotton pellet granuloma in rats.

Little is known about the effectiveness of bee products on chronic inflammation. In this experimental study, it was aimed to investigate and compare the anti-inflammatory activities of honey, propolis, royal jelly, pollen and bee bread, for the first time in the literature. In the study, 48 Sprague Dawley female albino rats weighing 200 ± 20g were used and bee products were administered by oral gavage method. Healthy, control, honey, propolis, pollen, royal jelly and bee bread groups were randomized. Chronic inflammation was created by cotton pellet method. For the treatments, 1g/kg of honey, 300mg/kg/day of pollen, 100mg/kg/day of propolis, 500mg/kg/day of bee bread and 100mg/kg/day of royal jelly were given for seven days. One week later, cotton pellets were removed, and the pro-inflammatory and anti-inflammatory cytokine levels of the blood samples were measured and compared statistically. It was found that honey, propolis, pollen, bee bread and royal jelly had statistically significant anti-inflammatory activities and significantly reduced pro-inflammatory cytokine levels (p < 0.001). Among the anti-inflammatory cytokines, pollen, bee bread and propolis were found to increase the levels of IL-4, IL-10 and IL-1RA the most. Among the pro-inflammatory cytokines, pollen, bee bread and propolis were the ones that decreased IL-6 and TNF-α levels the most; Pollen, bee bread and honey were found to decrease IL-1β the most (p < 0.001). It was found that all bee products have significant anti-inflammatory activities. The highest anti-inflammatory activity was found with pollen administration, followed by bee bread and propolis.

Toxicity Test of Sentul Fruit (Sandoricum koetjape) Peel Extract on Mice

Background : Sentul fruit peel extract has an antibacterial activity since it contains saponin, flavonoid, phenol, and tannin. Hence, it can be utilized in oral infection treatment. The safety level of herbal medicines needs to be studied by using a toxicity test. The study aims to discover the toxicity of Sentul fruit peel extract. Subjects and Method : The study was conducted in the laboratory of the Faculty of Food Technology of Warmadewa University and the laboratory of the Faculty of Medicine and Health Sciences of Warmadewa University. The independent variables of the study were the various doses of Sentul peel extract administered orally. The dependent variable was an acute toxicity test. The toxicity test in mice used an experimental study design in the laboratory that was observed qualitatively and quantitatively. The animals used were 25 male white mice (Mus musculus) and were divided into 5 groups. Data were collected based on the results of examinations from the laboratory and subsequently analyzed qualitatively and descriptively. Results : Based on the results of the LD50 Toxicity Test on Mice, Sentul peel extract samples did not cause toxic symptoms in the form of decreased heart activity, convulsions, decreased movement activity, and slow breathing. The administration of Sentul peel extract was categorized as non-toxic because mice do not experience abnormal symptoms and there was no death after the administration of the extract using the oral gavage method at all doses for 14 days, thus Sentul peel extract was safe to use as a medicinal ingredient. Conclusion : Sentul peel extract is categorized as non-toxic because mice do not experience abnormal symptoms and no death occurs. Keywords : Sentul peel, extraction, oral infection, mice, toxicity Correspondence : I Nyoman Wirata, Health Polytechnic of the Ministry of Health Denpasar. Jl. Sanitasi No.1, Sidakarya, South Denpasar, Denpasar City, Bali 80224. Email: wiratainyoman@gmail.com. Mobile: 08123649998. Indonesian Journal of Medicine (2023), 08(01): 114-120 https://doi.org/10.26911/theijmed.2023.08.01.11

The effect of capsaicin on TBARS and TAS in rats with hypothyroidism

In this study, capsaicin was administered to rats with experimental hypothyroidism. İt was aimed to determine the changes in plasma levels of thiobarbituric acid reactive substances (TBARS), which are indicators of oxidative stress, and total antioxidant capacity (TAS), which is one of the components of antioxidant defence mechanisms. A total of 32 healthy male Wistar Albino rats weighing 300-350 g, approximately 12 weeks old, were used as animal material in the study. Rats were divided into four equal groups control (K), Capsaicin (C), Hypothyroid (H) and capsaicin + Hypothyroid (CH). During the 30-day trial period, (10mg / kg / day) capsaicin was administered to the rats in group C by oral gavage per animal. In group H, 6-n-propyl-2-thiouracil (PTU) was added daily to their drinking water at 0.05% weight/volume (W/V). In the CH group, 10 mg/kg/day of capsaicin was administered by oral gavage method and 0.05% weight / volume (W / V) of PTU was added to drinking water. At the end of the application, we obtained plasma and serum samples from the subjects in the groups under general anaesthesia (thiopental anaesthesia, 40 mg/kg) and by taking sufficient amount of blood from the heart by cardiac puncture. We determined thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), free T3 (fT3), total thyroxine (TT4) and free T4 (fT4) levels from serum samples, and TBARS and TAS levels from plasma samples. In conclusion, in the light of the data obtained in this study, we determined that lipid peroxidation and oxidative stress occur in hypothyroidism. However, we concluded that the application of capsaicin is partially sufficient to maintain the oxidant/antioxidant balance.

Effect of vitamin B3 supplementation on glutathione redox cycle

In this study, the effect of vitamin B3 supplement given to rats was investigated on glutathione redox cycle by looking at glutathione peroxidase and glutathione s transferase activities. 20 Wistar albino male rats were used. Vitamin B3 supplement was given to one of the two groups that were formed. The other group was determined as the control group. 360 mg/kg/day vitamin B3 supplement was given by oral gavage method for 10 days. At the end of 10 days, intracardiac blood samples were taken. Glutathione peroxidase activity level was determined as 1033.44±198.05 U/L in the vitamin B3 supplement group and 526.00±99.54 U/L in the control group. The glutathione peroxidase activity level of the vitamin B3 supplemented group was found to be statistically significantly higher than the glutathione peroxidase activity level of the control group (p

Sıçan beyninin deneysel periodontitis modelinde DDD ve KAFE uygulamasının toplam antioksidan ve toplam oksidan düzeyleri üzerine etkileri

Aim: Observing the effects of caffeic acid phenethyl ester (CAPE) and/or low dose doxycycline (LDD) on total antioxidant and oxidant status of brain in experimental periodontitis is the purpose of the study.Methods: 48 male Wistar albino rats were designed as the following: control group (C, n=8), periodontitis + CAPE group (PC, n=10), periodontitis + LDD (PD, n=10), periodontitis + LDD + CAPE group (PCD, n=10), and periodontitis group (P, n=10). The time period for the experiment was 14 days. 10µmol/kg/day of CAPE was administered using an intraperitoneal injection (IP). 10 mg/kg/day of LDD was administered using an oral gavage method. Histopathological changes were evaluated.Results: Beneficial results were seen in all of the groups after LDD and/or CAPE administration on decreasing the alveolar bone loss level and oxidative stress. All of the experimental groups showed signs of periodontitis with alveolar bone loss. The P group leads with the most alveolar bone loss compared to the other periodontitis groups and the lowest group was the PC group in the periodontitis groups. The evolution of alveolar bone loss from high to low was that group P, group PD, group PCD, group PC, and group C (P &amp;lt; 0.05). However, there is no statistical difference between brain total antioxidant status and brain total oxidant status average values according to brain groups (p &amp;gt; 0.05).Conclusion: The combination of LDD and CAPE are not significantly different when applied alone or together on oxidative status. But both of the agents have beneficial effects on reducing the oxidative stress and tissue damages.

ABELMOSCHUS ESCULENTUS ADVERSE EFFECT ON THE SPLENIC CYTO-ARCHITECTURAL AND MORPHOLOGICAL INTEGRITY OF MALE WISTAR RATS

Background: Abelmoschus esculentus herbaceous hairy annual plant of the mallow family is widely consumed globally. High consumption of this plant may compromise the immune system, if it affects the functions of the spleen, whereas, the spleen is the main filter for blood-borne pathogens and antigens, as well as a key organ for iron metabolism and erythrocyte homeostasis. Objective: Our study was aimed at determining the possible toxicological effects of Abelmoscus esculentuson on the spleen of adult Wistar rats. Methods: Twenty-one (21) adult Wistar rats weighing about 150-170g were used for this study and were divided into three (3) groups of 7 animals each (n=7). Groups (I-III) received; normal rat feed and water, a low dose of Abelmoschus esculentus 1.0mg/kg BW and a high dose of Abelmoschus esculentus 3.0mg/kg BW respectively. All extracts were given daily by the oral gavage method for fourteen (14) days. Twenty-four hours after the last administration, the animals were sacrificed by cervical dislocation. The spleen was harvested, weighed, and fixed in 10% buffer formalin, sectioned, and processed for microscopic studies. Results: Following the administration of Abelmoschus esculentus, there was a significant increase in the test group. Also, histological observation showed Abelmoschus esculentus could result in various grades of degenerative changes, while prolonged intake at high concentrations may cause adverse effects on the cells of the spleen which may alter the functionality of the spleen. Conclusion: Hence, herbal remedies may help improve organ health, but can cause serious side effects if taken inappropriately.

Nephroprotective effect of apilarnil in lipopolysaccharide-induced sepsis through TLR4/NF-κB signaling pathway

AimsIn this study, we aimed to investigate the protective effect of apilarnil on kidney damage in the sepsis model induced by LPS. Main methods64 Sprague Dawley adult male rats were randomly divided into eight groups; control group, groups in which 0.2, 0.4 and 0.8 g/kg/bw apilarnil (API) was applied by oral gavage method for 10 days, LPS group in which 30 mg/kg/bw lipopolysaccharide (LPS) administered as intraperitoneally, groups in which LPS + 0.2, LPS+ 0.4 and LPS +0,8 API was applied. Six hour after the last administration the rats were anesthetized for euthanasia and kidney tissues were removed for RT-PCR analysis, immunohistochemical analysis and histopathologic analysis. Key findingAccording to the results of RT-PCR expression levels of IL-6, IL-1β, NF-κB, TNF-α and TLR4 were significantly reduced in the LPS + 0,8 API group. Immunoreactivity of TLR4, pNF-κB and TNF-α levels in the LPS + 0.8 apilarnil group were significantly lower than in the LPS and LPS + 0.2 apilarnil groups. Histologically, compared to the LPS group the glomerular damage score tended to decrease in the LPS + 0,4 API and LPS+ 0,8 API groups, while the tubulointerstitial injury score decreased especially in the LPS + 0,8 API group. SignificanceIn the present study, 0,8 g/kg dose of apilarnil promoted potential renoprotective effects which were achieved, at least in part, by the modulation of important markers of the local immune response in the model of LPS-induced sepsis.

Studies on the Effect of Aqueous Seed Extracts of Parkia Biglobosa on The Histology and Glycogen Profile of The Epididymis of Wistar Rats

This study was aimed at determining the effect of aqueous seed extract of Parkia biglobosa on the histology of the epidydimis of male wistar rats was studied. Twenty-one adult wistar rats weighing about 90-120g were use for this research work and were divided into three groups of 7 animals each. The control group was giving normal rat feed and water, the low dose group was administered (300mg/kgBw) of Parkia biglobosa extract and the high dose group was administered (500mg/kg) of the test substance. All extract were given daily by oral gavage method for thirty-one days. Twenty-four hours after the last administration, the animals in all the groups were sacrificed using cervical dislocation. The epidydimis were harvested, preserved, and fix in 10% buffer formalin and processed for hematoxylin and eosin (H&amp;E) staining and periodic acid-Schiff (PAS) staining methods for glycogen distribution. The result of the study shows a (P&lt;0.05) significant increase in the final body weight of the treated animals when compared with their initial body weight. The histological observation showed normal cytoarchitecture of the epididymis in the Control group. There was observable pathological appearance in the epididymis of the low dose group. However, there were prominent distortions in the high dose animals that received 500mg/kgBw of the extract. Histochemical observation shows a moderate PAS staining in the control group. While the treated groups reveals mildly stained cytoarchitechture of the epididymis.

Investigation on the Effect of &amp;lt;i&amp;gt;Parkia biglobosa&amp;lt;/i&amp;gt; Seed Extract on the Prostate of Male Wistar Rats

The research was directed at assessing the prostatic effect of the extract of <i>Parkia biglobosa</i> on the male Wistar rats. Twenty one (21) experimental rats weighing about 90-120 g and divided into three groups consisting of seven animals were used. The control group was fed with normal rat feed and water, while the experimental groups the low and high groups received (300 mg/kgBw) and (500 mg/kgBw) of the extract daily by oral gavage method for thirty one (31) days. All animals were sacrificed a day after the end of the extract administration by cervical dislocation. The prostate was removed, weighed and fix in 10% buffer formalin. Result showed that following administration of extract of <i>Parkia biglobosa</i>, a significant increase was observed in the test group. Histological observation show that administration of <i>Parkia biglobosa</i> at high dose and long duration could result to cystic changes in the epithelium. Study reveals that these focal areas of cystic changes are prognosis of benign prostatic hyperplasia. Other histological observation shows that administration of aqueous extract of <i>Parkia biglobosa</i> at high dose reveal congestion of blood vessels and functional hyperplasia characterized by increased in-folding of the glandular epithelium resulting in the decrease in glandular diameter. Histochemical observation reveals a weak PAS-positive epithelial nuclei and a weak to negative PAS- positive cytoplasm, studies reveal that this could cause atrophic tubules and reactive hyperplasia.

Food safety evaluation of papaya fruits resistant to papaya ring spot virus

Genetically modified (GM) papaya plant resistant to infection by Papaya Ring Spot Virus (PRSV) was successfully generated by cloning the coat protein (CP) gene of the PRSV. However, the food safety of GM foods remains controversial. This study assesses the food safety of two GM papayas, 16-0-1 and 18-2-4, and compares them with that of non-GM papaya, Tainung-2 (TN-2), using genetic and animal toxicity assays. Pulps of fresh papaya fruits were lyophilized and grounded before use. Three genotoxicity assays were performed: the Ames test of Salmonella typhimurium tester strains (TA98, TA100, TA102, TA1535 and TA1537); the chromosomal aberration of Chinese hamster ovary (CHO-K1) cells (in vitro); and micronucleus assays for mice (in vivo). Experimental results demonstrated that both non-GM and GM papaya fruits had no genotoxicity. Acute oral toxicity and 28-day repeated feeding toxicity tests for these papayas were performed via the oral gavage method for rats. All GM papaya fruit had no acute toxicity at a maximal dose of 5 g/kg body weight. Furthermore, the results of the 28-day study at 1 g/kg body weight in rats revealed no adverse-related effect in the body weight, feed consumption, hematology, blood biochemical parameters, organ weights and pathology in both GMs and non-GM papaya groups. In conclusion, PRSV-resistant papaya fruit lines 16-0-1 and 18-2-4 are comparable to their parent non-GM (TN-2) counterparts and are equivalent in food safety.

T178. MICROPIPETTE-GUIDED DRUG ADMINISTRATION (MDA) METHOD AS A NOVEL PHARMACOLOGICAL TREATMENT METHOD IN MICE: PRECLINICAL VALIDATION USING RISPERIDONE IN THE MATERNAL IMMUNE ACTIVATION MODEL OF NEURODEVELOPMENTAL DISORDERS

BackgroundPharmacological treatments in laboratory rodents remain a cornerstone of preclinical psychopharmacological research and drug development. There are numerous ways how acute or chronic pharmacological treatments can be implemented, with each method having certain advantages and drawbacks. To overcome the main disadvantages of conventional administration routes, we implemented and validated a novel treatment method in mice, which we refer to as the Micropipette-guided drug administration (MDA) method.MethodsThe MDA administration method is based on using sweetened condensed milk solution as vehicle for pharmacological substances, which motivates the animals to consume vehicle and/or drug solutions voluntarily in the presence of the experimenter. First, we measured the corticosterone and pharmacokinetic changes after the administration of a vehicle or drug (Risperidone) solution via traditional oral gavage or by MDA. We then conducted a chronic treatment paradigm in the maternal immune activation model (MIA). Offspring treatment with risperidone started on post-natal day 70 and lasted for a total of 6 weeks, with behavioral testing occurring during the last two weeks of the treatment window.ResultsIn a proof-of-concept study, we show that the pharmacokinetic profiles of the atypical antipsychotic drug, risperidone, are similar when administered via the MDA procedure or via the conventional oral gavage method. Unlike the latter, however, MDA did not induce the stress hormone, corticosterone. Furthermore, we assessed the suitability and validity of the MDA method in a mouse model of maternal immune activation, which is frequently used as a model of immune-mediated neurodevelopmental disorders. Using this model, we found that chronic treatment (> 4 weeks, once per day) with risperidone via MDA led to a dose-dependent mitigation of MIA-induced social interaction deficits and amphetamine hypersensitivity.DiscussionTaken together, the MDA procedure described represents a novel pharmacological administration method for per os treatments in mice, which is easy to implement, cost effective, non-invasive, and less stressful for the animals than conventional oral gavage methods. Moreover, it allows for a more consistent and continual control of the dosages administered to the animals compared to methods involving the dissolution of a substance in the drinking water or contained within the food of the animals.

Protective effect of oleuropein on ketamine-induced cardiotoxicity in rats.

The antioxidant and cardioprotective effects of oleuropein have been reported in several studies; however, its effect on ketamine cardiotoxicity has not been known yet. The aim of this study was to investigate the effects of oleuropein in ketamine-induced cardiotoxicity model in rats. A total of 28 male Wistar Albino rats were included in the study and they were randomly divided into four groups, each having seven rats. Group 1 (control): rats were given 1mL of DMSO by oral gavage method for 7days. Group 2 (ketamine): on the seventh day of the study, 60mg/kg ketamine was administered intraperitoneally. Then, 60mg/kg ketamine was administered intraperitoneally every 10min for 3h. Group 3 (oleuropein): rats were given 200mg/kg/day oleuropein by oral gavage method for 7days. Group 4 (oleuropein + ketamine): rats were given 1 × 200mg/kg oleuropein by oral gavage method for 7days. Furthermore, 60mg/kg ketamine was administered intraperitoneally on the seventh day of the experiment. Then, 60mg/kg ketamine was administered intraperitoneally every 10min for 3h. Serum cardiac marker (TnI, CK-MB and CK) levels were measured. Histopathological analysis was performed on a portion of the cardiac tissue. Cardiac tissue oxidative stress and antioxidant markers (MDA, GSH, GSH.Px and CAT), TNF-α, IL-6, NF-κB, COX-2 and Nrf-2 gene expressions, and protein conversion levels of related genes were determined. Data obtained showed that ketamine administration increased MDA (p < 0.001), TNF-α (p < 0.01), IL-6 (p < 0.01), COX-2 (p < 0.001) and NF-κB (p < 0.001) levels, as well as serum TnI (p < 0.001), CK-MB (p < 0.001) and CK (p < 0.01) levels whereas decreased GSH (p < 0.05) and Nrf-2 (p < 0.05) levels, as well as GSH-Px (p < 0.001) and CAT (p < 0.05) enzyme activities. Oleuropein administration was observed to decrease MDA, TNF-α, IL-6, COX-2, NF-κB, TnI, CK-MB and CK levels close to the control group and to increase GSH levels and GSH-Px and CAT enzyme activities close to the control group. This study showed that oleuropein administration reversed the increased oxidative stress and inflammation as a result of the use of ketamine and had protective effects on the heart.

Preclinical validation of the micropipette-guided drug administration (MDA) method in the maternal immune activation model of neurodevelopmental disorders

Pharmacological treatments in laboratory rodents remain a cornerstone of preclinical psychopharmacological research and drug development. There are numerous ways in which acute or chronic pharmacological treatments can be implemented, with each method having certain advantages and drawbacks. Here, we describe and validate a novel treatment method in mice, which we refer to as the micropipette-guided drug administration (MDA) procedure. This administration method is based on a sweetened condensed milk solution as a vehicle for pharmacological substances, which motivates the animals to consume vehicle and/or drug solutions voluntarily in the presence of the experimenter. In a proof-of-concept study, we show that the pharmacokinetic profiles of the atypical antipsychotic drug, risperidone, were similar whether administered via the MDA procedure or via the conventional oral gavage method. Unlike the latter, however, MDA did not induce the stress hormone, corticosterone. Furthermore, we assessed the suitability and validity of the MDA method in a mouse model of maternal immune activation, which is frequently used as a model of immune-mediated neurodevelopmental disorders. Using this model, we found that chronic treatment (>4 weeks, once per day) with risperidone via MDA led to a dose-dependent mitigation of MIA-induced social interaction deficits and amphetamine hypersensitivity. Taken together, the MDA procedure described herein represents a novel pharmacological administration method for per os treatments in mice that is easy to implement, cost effective, non-invasive, and less stressful for the animals than conventional oral gavage methods.

Protective effect of Melatonin and Ganoderma lucidum against the negative effects of extremely low frequency electric and magnetic fields in the periodontal tissues

Aim:The purpose of this study was to determine whether extremely low frequency electric and magnetic field (ELF-EMF) had any detrimental effects on periodontal tissue and to investigate, histologically and immunohistochemically whether melatonin (MLT) and Ganoderma lucidum (GL) had a protective role against these detrimental effects.&#x0D; Methodology:A total of 56 adults, male Wistar Albino rats were used in this study. Rats were divided into 7 equal groups and exposed to ELF-EMF, which was produced by a high voltage source, 8 hours / day for 26 days. GL (20 mg / kg / day) and MLT (10 mg / kg / day) were administered by the oral gavage and intraperitoneal method.&#x0D; Results: Fibrous degeneration in the periodontal membrane, inflammatory cell infiltration, connective tissue fiber organization, dilation, and hemorrhage in the blood vessels changes were determined in the periodontal tissue of the rats in groups I and IV. A statistically significant difference was determined in the groups treated with MLT and GL (p&lt;0.05).&#x0D; Conclusions: It has been determined that ELF-EMF exposure causes histological changes in the periodontal tissue of rats and that MLT and GL may protect against these effects.&#x0D; &#x0D; How to cite this article: Gül M, Yavaş MC, Dündar S. Protective effect of Melatonin and Ganoderma lucidum against the negative effects of extremely low frequency electric and magnetic fields in the periodontal tissues. Int Dent Res 2019;9(3):119-26.&#x0D; &#x0D; Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.