Male Wistar Albino Rats Research Articles

Impact of Opuntia ficus-indica Juice and Empagliflozin on Glycemic Control in Rats

Diabetes mellitus (DM) is a major global health concern characterized by high blood glucose levels. This study investigates the effects of Opuntia ficus-indica (cactus) juice and empagliflozin, both alone and in combination, on glycated hemoglobin (HbA1c) levels in healthy and streptozotocin-induced diabetic rats. Eighty Wistar albino male rats were divided into eight groups, with four groups being diabetic. Treatment options included cactus juice, empagliflozin, or both. HbA1c levels were measured at baseline and 100 days later using ELISA. In diabetic and non-diabetic rats treated with cactus juice or empagliflozin, HbA1c levels were significantly reduced, but diabetic rats had significantly lower HbA1c values than non-diabetic rats. The combined treatment provided no additional benefits over individual therapies. These findings indicate that cactus juice and empagliflozin effectively lower HbA1c levels, making their use a promising complementary approach to diabetes management. However, the combined treatment of Opuntia ficus-indica juice and empagliflozin did not yield additional reductions in HbA1c levels compared to individual treatments, with no significant synergistic effects observed throughout the study period. More research is needed to better understand the clinical applications and mechanisms in humans.

Selenium ameliorates oxidized phospholipid-mediated testicular dysfunction and epididymal sperm abnormalities following Bisphenol A exposure in adult Wistar rats.

Bisphenol A (BPA) is an endocrine-disrupting compound extensively utilized in the production of polycarbonate polymers and epoxy resins that, upon exposure, pose a significant threat to male reproductive health because of its estrogenic properties. Accumulating evidence suggests that BPA exposure disrupts the normal process of spermatogenesis, alters testicular morphology and function, and interferes with testicular steroidogenesis and hormonal signaling. However, the precise mechanism by which BPA affects testicular function remains unclear. In this study, we explored the mechanism underlying BPA-induced testicular abnormalities and evaluated the protective effects of Selenium (Se). Thirty-two adult male albino Wistar rats were divided into four groups, and BPA was administered at 50mg/kg body weight, with or without Se supplementation, for 30 days. Se supplementation (2.5mg/kg body weight) was initiated 1 week before BPA administration. BPA administration resulted in alterations in testicular architecture, characterized by basement membrane disintegration in the seminiferous tubules, reduced spermatogenic cell counts, and increased interstitial tubule noncellular space. Furthermore, BPA exposure increased the levels of oxidized phospholipids, lipid peroxides, and hydroxyl radicals and decreased the activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. In addition, BPA significantly reduced the activities of 3β- and 17β-hydroxysteroid dehydrogenases, interfering with testicular steroidogenesis. In rats, coadministration of Se and BPA reduced the levels of oxidized phospholipids and increased the activities of antioxidant enzymes, leading to improved testicular function and epididymal sperm parameters, suggesting that Se plays a critical role in alleviating endocrine disruptor-induced testicular dysfunctions in rats.

Investigating the hepatoprotective and antidiabetic properties of cryogenically pulverized Turkish propolis water extracts in streptozotocin-induced diabetic rats

Diabetes is a major global health crisis, affecting millions of people worldwide and necessitating the search for effective and safe treatments, leading to various complications, including liver damage. This study investigated the hepatoprotective and antidiabetic properties of cryogenically pulverized Turkish propolis water extracts (WBTP) in streptozotocin-induced diabetic rats.Propolis samples were collected from the West Black Sea Region of Turkey and prepared as -80 °C (PP-80) and -196 °C (PP-196) water extracts. Thirty male Wistar albino rats were divided into five groups: normal control, diabetic control, diabetic + PP-80 (250 mg/kg), diabetic + PP-196 (250 mg/kg), and diabetic + metformin (250 mg/kg). After 35 days of treatment, various parameters were evaluated, including body weight, blood glucose, glycated hemoglobin (HbA1c), serum biochemistry, antioxidant enzyme activities, and histopathology of the pancreas.The results showed that WBTP extracts, especially PP-80, significantly improved body weight and reduced blood glucose and HbA1c levels. Analysis of lipid profiles revealed improvements in HDL, LDL, triglycerides, and total cholesterol levels with WBTP treatment. The antioxidant defense systems were also enhanced in the WBTP-treated groups. Histopathological examination revealed that WBTP extracts mitigated pancreatic tissue damage in the diabetic rats.In conclusion, the WBTP extracts possess hepatoprotective and antidiabetic properties, suggesting a promising avenue for further research. It emphasizes the importance of addressing both diabetes and hepatopathologies concurrently and highlights WBTP extracts as natural and potentially safer alternatives to synthetic antidiabetic drugs. Specifically, PP-80 extracts demonstrate robust effects in managing diabetes and associated liver complications in streptozotocin-induced diabetic rats, indicating their therapeutic potential.

Bupropion Increased More than Five Times the Systemic Exposure to Aripiprazole: An In Vivo Study in Wistar albino Rats

Background/Objectives: In psychiatric disorders, antipsychotics and antidepressant medication are often administered together. Aripiprazole, a third-generation antipsychotic drug, is extensively metabolized by CYP2D6 and CYP3A4 isoenzymes, while bupropion, used in depressive disorders, is known as a moderate or strong CYP2D6 enzyme inhibitor. This in vivo experiment aimed to assess the presence of a pharmacokinetic drug interaction between aripiprazole and bupropion and its magnitude on the systemic exposure of aripiprazole. Methods: 24 healthy Wistar albino male rats were included in two study groups. A single dose of 8 mg/kg aripiprazole was given to rats in the reference group, while the test group received repeated doses of bupropion for 6 days, followed by a single dose of aripiprazole. An LC-MS/MS method was developed for the concomitant quantification of aripiprazole and its active metabolite, dehydroaripiprazole, and non-compartmental analysis was employed to assess their pharmacokinetic parameters. Results: The mean AUC0-∞ of aripiprazole increased 5.65-fold (1117.34 ± 931.41 vs. 6311.66 ± 2978.71 hr·ng/mL), the mean Cmax increased by 96.76% and the apparent systemic clearance decreased over 9-fold after bupropion repeated doses. The exposure to aripiprazole’s active metabolite increased as well, having a 4-fold increase in the mean AUC0–∞ (from 461.13 ± 339.82 to 1878.66 ± 1446.91 hr·ng/mL) and a 2-fold increase in the mean Cmax. Conclusions: The total exposure to the aripiprazole parent compound and active moiety significantly increased after bupropion pretreatment in this preclinical in vivo experiment. Clinical studies should further establish the significance of this interaction in humans.

Comparative study of the protective effects of coenzyme Q10 and cinnamon extract on possible kidney damage and dysfunction of amiodarone in rats.

An increase in free oxygen radicals and proinflammatory cytokines and decrease in intracellular adenosine triphosphate account for the nephrotoxic effect of amiodarone. This study investigated the protective effects of Coenzyme Q10 (CoQ10), cinnamon extract (CE) and the combination of the two (CoCE) on possible amiodarone-induced renal injury in rats. Thirty male albino Wistar rats were cetegorized into healthy (HG), amiodarone (ADG), CoQ10 + amiodarone (CoQA), CE + amiodarone (CEA), and CoCE + amiodarone (CoCEA) groups. First, CoQ10 (10mg/kg) and CE (100mg/kg) were orally given. After 1h, 50mg/kg amiodarone was orally given to all groups except for HG. Amiodarone, CoQ10, and CE administration was continued orally at the indicated doses once daily for 10days.Then, blood samples were collected from all groups to determine creatinine, blood urea nitrogen (BUN), and kidney injury molecule (KIM-1) levels, followed by euthanasia and removal of kidney tissues. Oxidative stress and inflammatory parameters were analysed in the tissue samples. Histopathological examination was also performed on the tissues. Amiodarone increased malondialdehyde levels and decreased total glutathione, superoxide dismutase, and catalase levels (p < 0.001). Amiodarone increased the expression and tissue levels of tissue nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1β and interleukin-6, and led to increases in serum creatinine and BUN and KIM-1 levels (p < 0.001). Amiodarone also caused histopathological damage (p < 0.001).CoQ10, CE and especially CoCE inhibited biochemical changes and tissue damage (p < 0.001). Although CoQ10, CE, and CoCE effectively prevent amiodarone-induced oxidative and inflammatory nephrotoxicity, CoCE appears to be superior.

Intracavernosal mesenchymal stem cell therapy in ischaemic priapism: an experimental study.

The most common form of priapism is ischaemic and its prevalence in men has increased in recent years as a result of intracavernosal drug use. Currently, there is no approved specific treatment for ischaemic priapism other than cavernosal aspiration, which can only provide detumescence. This study aims to evaluate the efficacy of intracavernosal mesenchymal stem cell (MSC) therapy in an ischaemic priapism model. Thirty male Wistar albino rats were divided into three groups: sham (n = 6), priapism (n = 12) and priapism + MSC treatment (n = 12). The experimental groups were also divided into 1 and 12h subgroups of ischaemic priapism. The experimental model was created using a vacuum erection device and constrictive tape technique, and intracavernosal MSC were applied immediately after the tape was removed. After 4weeks, intracavernosal pressures (ICPs) and systemic mean arterial pressure (MAP) were measured. Penectomy was then performed to assess histopathological and molecular changes in the rats' penile tissues. In the ischaemic priapism model, MSC therapy showed significant improvements in peak and mean ICPs and mean ICP/MAP ratio. Histopathological analysis showed significant increases in smooth-muscle/collagen ratio and e-NOS and n-NOS expression. Although there was a decrease in fibrosis, it was not significant. At the molecular level, there were significant decreases in TGF-beta and VEGF mRNA expression, whilst NGF and BDNF mRNA-expression levels showed significant increases with MSC therapy. In terms of ICPs, the therapy showed more significant improvements in short-term priapism. However, when looking at histopathological and molecular parameters, the therapy had positive effects on a wider range of parameters in the long-term priapism. MSC treatment improved cavernosal physiology and had positive effects at the histopathological and molecular level in the ischaemic priapism model.

PTZ KINDLING MODEL: EVALUATION OF EEG FACTOR AND BIOCHEMISTRY PARAMETERS UNDER THE INFLUENCE OF RAMELTEON

Many selective synthetic melatonin receptor agonists have anticonvulsant/anti-epileptogenic properties. These agonists bind to melatonin receptor 1 (MT1) and receptor 2 (MT2), causing their activation. Therefore, we evaluated the anticonvulsant effect of Ramelteon (RMLT) as a melatonin agonist in the PTZ (Pentylenetetrazol)-kindling model. In the study, 36 male Wistar Albino rats were assessed in 6 groups (Sham, PTZ, dimethylsulphoxide (DMSO), Valproic acid (VPA) (150 mg/kg) + PTZ, RMLT (30 mg/kg)+PTZ, VPA+RMLT+PTZ). Cortical electroencephalography (EEG) data were recorded for all groups. Seizures were scored according to the Racine scale. Seizure scores and onset times of the first myoclonic movements were compared in EEG traces. Total antioxidant status (TAS), total oxidant status (TOS), catalase, myeloperoxidase (MPO), and Thiol levels were measured in serum samples. Also, Calcineurin (CaN), Neuropeptide-Y (NPY), Neuron Specific Enolase (NSE), and S100B levels were measured in brain tissue samples. There was a significant difference between the PTZ and PTZ+Valproic acid+RMLT groups for the onset of the first myoclonic movements and the rate of spikes in the EEG traces in Racine's convulsion stages (P 0.05). RMLT has anticonvulsant properties. Additionally, the receptor preference of RMLT can be investigated.

Long-term consumption of aspartame &amp; cancer risk

Artificial sweeteners, specifically aspartame, are present in everyday modern diets due to their low-calorie content and high level of sweetness. They are often used as sugar substitutes to promote weight loss and manage diabetes. Despite their widespread use and approval by regulatory bodies such as the U.S. Food and Drug Administration (FDA), concerns about the safety and potential carcinogenicity of artificial sweeteners persist. This research paper delves into the controversy surrounding aspartame, which was classified as possibly carcinogenic to humans by the International Agency for Research on Cancer (IARC) in 2023. By reviewing literature and analyzing studies published between 2000 and 2024, this paper explores aspartame’s metabolism in the human body, its by-products, and its biological effects. The article also delves into a notable experimental study involving male Wistar albino rats that demonstrated significant biochemical changes, histological liver damage, and gene expression alterations at high doses of aspartame, indicating potential cancer risks. The findings underscore the need for further research to clarify the biochemical and molecular mechanisms linking artificial sweeteners to cancer while emphasizing cautious consumption and reevaluation of safety guidelines.

Effects of Methanolic Extracts of Anisopus mannii Leaves on Blood Glucose and Organ Weights of Wistar Rats with Alloxan Induced-Diabetes

This study looked at the impact of Anisopus mannii methanolic leaf extract on Wistar rats’ organ weights and alloxan-induced diabetes. For this investigation, a total of 20 male Wistar (albino) rats weighing between 80 and 150 g were used. Four groups of rats were randomly assigned. 1: Normal control; 2: Negative control; 3: Positive control (treated alloxan induced-diabetic with 5 mg/kg metformin); 4: alloxan induced-diabetic treated with 200 mg/kg of methanolic A. mannii leaf extract. The findings of the study show there was a significant difference in the blood glucose levels between the diabetic rats treated with metformin and the diabetic rats treated with A. mannii methanolic leaves extract on days 7 and no significant difference in day 14. The fasting blood glucose level in the diabetic rats treated with A. mannii on day 7 reduced from 167.00±19.76 mg/dL to 88.08±11.78 mg/dL on day 14. the liver weights (3.69±0.21 g) of the diabetic rats treated with the extract were significantly lower than those of the diabetic rats treated with metformin (4.86±0.16 g), and it was also within the weight for normal control which were non-diabetic (3.93±0.29 g). The kidney weights of the diabetic rats treated with the extract (1.13±0.18 g) were significantly higher than those of the diabetic rats treated with metformin (0.96±0.03 g). This work unequivocally shows that, in rats given alloxan to produce diabetes, A. mannii extract was able to substantially lower fasting blood glucose levels and shield the kidneys and liver from harm in just two weeks..

Antioxidant and hepatoprotective effects of methanolic seed extract of Telfairia occidentalis on carbon tetrachloride induced hepatic damage in wistar rats

BackgroundTelfairia occidentalis, a drought-resistant vegetable in West Africa, was studied for its hepatoprotective and therapeutic effects on carbon tetrachloride-induced liver injury in wistar rats. Earlier, the study found that the methanolic seed extract of T. occidentalis contained various phytochemicals, including tannins, flavonoids, terpenoids, alkaloids, phenols, cardiac glycosides, and steroids.MethodologyRats were treated with Telfairia occidentalis methanolic seed extract after being exposed to carbon tetrachloride for a duration of 14 days. Thirty (30) male and female Albino Wistar rats were used, and were divided into six (6) groups of five (5) animals apiece. The groups were as follows: Pre-treatment group (TOSE + CCl4 Group): this group received normal diet, water, and seed extract 400 mg/kg in 0.5 mL of olive oil for 13 days, then carbon tetrachloride 2 mL/kg in olive oil on the 14th day; Curative group (CCl4 + TOSE): this group received carbon tetrachloride 2 mL/kg administered on day 1 then seed extract for the remaining 13 days; and Concurrent Group (2CCL4 + TOSE); carbon tetrachloride 2 mL/kg given twice a week for 14 days (2 weeks) and seed extract daily.ResultsThe results of the study showed that, in comparison to the normal control group's AST (89.52 ± 4.91), ALT (33.60 ± 2.32), and ALP (31.03 ± 0.97), the group that received CCl4 alone had significantly higher serum levels of these indices AST (122.43 ± 3.89), ALT (85.80 ± 3.22), and ALP (42.78 ± 1.83) as well as liver tissue necrosis. Telfairia occidentalis seed extract treatment prevented liver damage and restored liver architecture, as evidenced by significantly lower values of ALT, ALP, and AST (84.73 ± 6.28#, ALT (52.40 ± 1.63), ALP (25.52 ± 1.60), and ALT (71.40 ± 1.69, ALP (27.68 ± 1.95#)) following or before CCl4 administration. Furthermore, the data showed that GPx, SOD, and CAT activities were significantly (P < 0.05) lower in the rats given CCl4 than in the control group. The extract alone considerably raised the antioxidant levels in comparison to the control.ConclusionThe study found that the treatment with Telfairia occidentalis seed extract significantly increased the activities of glutathione peroxidase and SOD in rats, and also reduced levels of AST, ALT, and ALP. Authenticating the therapeutic benefits of Telfairia occidentalis seed extract.

Agmatine Improves Oxidative Stress Profiles in Rat Brain Tissues Induced by Sodium Azide

Introduction: The brain is highly susceptible to oxidative damage due to excessive oxygen tension, a high concentration of oxidizable substrates, and low antioxidant capacity. Consequently, oxidative stress is linked to several brain disorders and neurodegeneration. Sodium azide is a cytochrome oxidase inhibitor that promotes neurodegeneration by enhancing the release of excitotoxins and inducing oxidative stress through the peroxidation of membrane lipids. This process results in the release of intra-mitochondrial Ca+2 and H2O2 (ROS Dependent-Ca+2 release). Agmatine, a biogenic amine, is also referred to as a free radical scavenger, protecting the brain from membrane collapse, apoptosis, and mitochondrial swelling. Objective: This study was designed to identify the antioxidative effects of agmatine on sodium azide- induced oxidative stress in brain tissues. Methodology: Twenty-four male albino Wistar rats were allocated into two groups: a control group receiving water and a test group administered sodium azide (5 mg/kg, intraperitoneally) for a duration of 14 days. Subsequently, the animals were further subdivided and treated for an additional two weeks with either water or agmatine (100 mg/kg). Behavioral assessments were performed onehour post-agmatine administration, and brain homogenates were prepared for biochemical analyses. Results: The agmatine-treated group exhibited a significant increase (P&lt;0.01) in both the number of entries and the time spent in the light box and the open arms of the light/dark transition box and elevated plus maze tests, respectively. Additionally, agmatine administration significantly enhanced (P&lt;0.01) the total number of squares crossed in the open field test. Biochemical assessments revealed that agmatine treatment significantly reduced (P&lt;0.01) the levels of reactive oxygen species and malondialdehyde. Moreover, it significantly increased (P&lt;0.01) the levels of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and glutathione compared to the control group. Conclusion: The present study revealed that agmatine has substantial effects on oxidative and antioxidant enzyme levels in sodium azide-induced oxidative stress. Agmatine-treated rats exhibited decreased reactive oxygen species levels and improvements in behavioral impairments resulting from sodium azide administration.

Effects of four-week lasting aerobic treadmill training on hepatic injury biomarkers, oxidative stress parameters, metabolic enzymes activities and histological characteristics in liver tissue of hyperhomocysteinemic rats.

Disruptions in homocysteine (Hcy) metabolism may increase the liver's susceptibility to developing conditions such as alcoholic liver disease, viral hepatitis, hepatocellular carcinoma (HCC), and cirrhosis. The aim of this study was to examine effects of aerobic treadmill training on hepatic injury biomarkers in sera, oxidative stress parameters, the activity of metabolic enzymes, and histological characteristics in the liver tissue of rats with experimentally induced hyperhomocysteinemia. Male Wistar albino rats were divided into four groups (N = 10, per group): C-saline 0.2mL/day sc. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; H-homocysteine 0.45µmol/g b.w. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; CPA-saline 0.2mL/day sc. 2×/day for 14days + aerobic treadmill training for 28days; and HPA-homocysteine 0.45µmol/gb.w. 2×/day for 14days + aerobic treadmill training for 28days. The serum albumin concentration was decreased in both physically active (PA) groups compared to sedentary groups. Concentration of malondialdehyde in liver tissue homogenates was lower in both PA groups compared to the H group. The total lactate dehydrogenase and malate dehydrogenase activities were significantly elevated in the HPA group compared to the C and H groups. Activities of aminotransferases in sera samples, and activities of catalase and superoxide dismutase in liver tissue did not significantly differ between groups. No significant histological changes were found in liver tissue in groups. This study demonstrated that aerobic treadmill training can reduce lipid peroxidation in liver tissue under hyperhomocysteinemic conditions, providing a protective effect. However, hyperhomocysteinemia can alter energy metabolism during aerobic exercise, shifting it toward anaerobic pathways and leading to elevated lactate dehydrogenase activity in the liver. Given that conditions like hyperhomocysteinemia are associated with an increased risk of cardiovascular diseases and liver damage, understanding how exercise influences these dynamics could guide therapeutic approaches.

Restorative Effect of Consuming Red Wine Against Adverse Changes in the Brain of Rodents Exposed to Beer

Objective: There is a surge in the availability of alcoholic products accompanied by a high rate of consumption despite increasing neurological problems. Aim of this study is to determine whether regular intake of brewed beer and red wine affects the microanatomy of the cerebral cortex, hippocampus and brain weight. Materials and Methods: 20 male albino Wistar rats were assigned to four groups of five animals each. Group A, the control was given distilled water; Group B was administered 5 mL/kg body weight of beer; Group C received 5 ml/kg of red wine; and Group D was dosed with 5 ml/kg of beer and followed with 5 ml/kg of red wine. Daily treatments by gavage lasted 15 days, and animal subjects were euthanized via cervical dislocation on day 16. Individual brains were collected and weighed using an electronic scale (SF-400) and afterwards dissected to obtain tissue samples from the cerebral cortex and hippocampus, immediately fixed in 10% formalin for micro-anatomic studies. The paraffin embedding method was used for histological preparation while sections were cut at 5 µm and stained with hematoxylin and eosin. Brain weight was analyzed using the Statistical Product and Service Solutions (SPSS) software via one-way analysis of variance. Results: Histopathological changes including intracerebral haemorrhage and loss of pyramidal neurons observed in group B (beer) samples were not visible in Group D (beer plus red wine), while no microstructural changes occurred in group C (red wine) sections when compared with the control. The output of statistical analysis showed a non-significant reduction in brain weight of group B, whereas a significant increase was noticed in group C while group D showed a non-significant increase. Conclusion: These findings indicate that red wine counteracts beer-induced changes in brain morphology, hypothesising the neuroprotective effect of the wine.

Exploring the protective role of green tea extract against cardiovascular alterations induced by chronic REM sleep deprivation via modulation of inflammation and oxidative stress

BackgroundChronic Rapid eye movement (REM) sleep deprivation has been associated with various cardiovascular alterations, including disruptions in antioxidant defense mechanisms, lipid metabolism, and inflammatory responses. This study investigates the therapeutic potential of green tea extract (GTE) in mitigating these adverse effects.MethodsA total of 24 male Wistar albino rats were used in this study and divided into the control group (n = 8), Chronic-REM Sleep Deprivation (CRSD) Group (n = 8) and Chronic-REM SD + Green Tea 200 (CRSD + GTE200) Group (n = 8). After 21 days, a comprehensive analysis of paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), proinflammatory cytokines, and lipid profiles in aortic tissue, heart tissue, and serum was conducted in a sleep-deprived rat model.ResultsChronic REM sleep deprivation led to a significant reduction in PON1 and ARE levels in aortic (p = 0.046, p = 0.035 respectively) and heart tissues (p = 0.020, p = 0.019 respectively), indicative of compromised antioxidant defenses. MDA levels increased, and NOx levels decreased, suggesting oxidative stress and impaired vascular function. Lipid profile alterations, including increased triglycerides and total cholesterol, were observed in serum. Elevated levels of inflammatory cytokines (IL-6 and TNF-alpha) further indicated an inflammatory response (p = 0.007, p = 0.018 respectively). GTE administration demonstrated a protective role, restoring antioxidant enzyme levels, suppressing lipid peroxidation, and improving NOx levels.ConclusionThese findings suggest the therapeutic potential of GTE in alleviating the cardiovascular impairments of chronic REM sleep deprivation, emphasizing its candidacy for further clinical exploration as a natural intervention in sleep-related disorders and associated cardiovascular risks.

Effects of Apelin-13 on auditory system in STZ-induced diabetic rats

AimDamage to the auditory pathways is one of the complications of diabetes. The aim of this study was to investigate the potential therapeutic effects of apelin-13 in the auditory pathways of rats with experimentally induced diabetes by examining its effect on auditory brainstem responses, cochlear oxidative stress and inflammatory cytokines. MethodsThirty-two male Wistar albino rats were divided into four groups: sham control, diabetes, apelin and diabetes + apelin. A single dose of 45 mg/kg streptozotocin (STZ) was administered to induce diabetes. The apelin group received 50 µg/kg apelin-13 for seven days intraperitoneally (ip). At the end of the apelin and STZ applications auditory brainstem responses (ABR) was recorded. At the end of the experiment, cochlea was removed and biochemical analyzes were performed. ResultsIn ABR recordings, the latencies of wave V in diabetic group were observed to be longer than those of the control, with the apelin treatment exhibiting a partial reversal of this situation, particularly at specific frequencies and intensity levels. Apelin treatment leads to a significant increase in total antioxidant status (TAS) and a reduction in total oxidant status (TOS) and oxidative stress index (OSI) in cochlea compared to diabetic groups. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1 beta) in cochlear tissue were found to be significantly reduced in the apelin-treated group compared to the diabetic group. ConclusionApelin-13 may have a protective effect on the auditory system and may be proposed as a potential new therapeutic strategy for the management diabetic auditory impairment.

Chronic pregabalin treatment reduced anxiety, and acute pregabalin treatment increased depression-like behaviors in rats

BackgroundPregabalin is an antiepileptic drug that binds to the alpha-2/delta unit at presynaptic voltage-dependent calcium channels. We aimed to investigate the effect of acute and chronic pregabalin administration on anxiety and depression-like behaviors.MethodsFifty-six male Wistar albino rats were divided into seven groups: control, vehicle, and five different dose groups (5, 10, 30, 60, and 100 mg/kg). Pregabalin was administered for two weeks. Depression-like behaviors were evaluated by Forced swimming test. Anxiety-like behavior (ALB) was evaluated by Open field test (OFT), Elevated Plus Maze (EPM), and light-dark box. Subjects underwent the forced swimming test (FST) after the first dose, while the open field test (OFT), elevated plus maze (EPM), and light-dark box (LDB) were performed after two weeks of treatment. Further sucrose preference test was conducted to evaluate anhedonia until the end of the experiment.ResultsIn the forced swimming test, depression-like behaviors increased after acute single-dose administration of 10, 30, 60, 100 mg/kg pregabalin. According to OFT results, chronic 100 mg/kg pregabalin showed anxiolytic effects by decreasing grooming, and freezing behaviors. In addition, 100 mg/kg chronic pregabalin administration significantly increased the time spent in the central region, the number of entries to the center, and the unsupported rearing number without causing any change in locomotor activity. According to EPM results, both chronic 60 and 100 mg/kg pregabalin treatments showed anxiolytic effects by increasing open arm time and head dipping behavior. In addition, 60 and 100 mg/kg chronic pregabalin administration significantly decreased stretch attend posture. All pregabalin administrations between 5 and 100 mg/kg displayed anxiolytic effects in the LDB. Sucrose preference was above 65% for the duration of all experiments and subjects did not show anhedonia.ConclusionAcute pregabalin treatment triggered depression-like behaviors. Anhedonia, which may be associated with depression, was not observed during chronic treatment. Moreover, chronic treatment with pregabalin revealed potent anxiolytic effects in different behavior patterns and doses for all tests of unconditional anxiety. In particular, 100 mg/kg chronic pregabalin administration decreased anxiety-like behaviors in all experiment setups. Although the anxiolytic effect was demonstrated in chronic treatment, acute treatment of pregabalin induced depression-like behaviors, and thus in clinical practice should be done with caution, especially in patients with anxiety-depression comorbidity.

The effect of edoxaban on apoptosis in an abdominal aortic aneurysm model in rats

Background: This study aimed to evaluate the effects of edoxaban, which is used in venous thrombosis, systemic embolism, and stroke, on an aortic aneurysm model and to demonstrate the pharmacokinetic and molecular effects of edoxaban through the induction of apoptosis. Methods: In this double-blind experimental study, 21 Wistar albino male rats (mean weight: 290 g; range, 280 to 300 g) were divided into three groups: the sham group (n=7), the abdominal aortic aneurysm (AAA) group (n=7), and the AAA-edoxaban group (n=7). Edoxaban 10 mg/kg was given to the AAA-edoxaban group by oral gavage daily for 30 days. At the end of 30 days, the aneurysmal aorta was surgically removed and histologically examined. The abdominal aorta was surgically exposed and wrapped with a calcium chloride (0.5 mol/L) sponge for 10 min. Results: Immunohistochemically, aortic sections were marked with caspase-3 and caspase-9 antibodies. It was observed that the pathways that trigger apoptosis (caspase-3 and caspase-9; p&lt; 0.004 and p&lt; 0.005, respectively) were significantly reduced in the AAA-edoxaban group compared to the AAA group. In the AAA-edoxaban group, it was observed that the expansion in aortic diameter and the deterioration in the elastic fibril structure in the aortic aneurysm were decreased as a result of edoxaban treatment. Edoxaban treatment was observed to reduce cell death in both the tunica intima and tunica media. Conclusion: This study provided strong evidence of the protective effect of edoxaban on aortic aneurysm-related vascular damage by reducing apoptosis and mitophagy.

The Effects of Phenyramidol and Diclofenac Treatment on Fracture Healing in Rats.

Fracture healing or nonunion refers to a process in which many factors interact. In this study, we aimed to evaluate the radiological, histological, and biomechanical effects of phenyramidol and diclofenac, which are frequently used to treat post-fracture ture pain worldwide, on fracture healing and nonunion in a rat femur fracture model. In this study, 72 male Wistar-Albino rats aged 2-3 months and weighing 250 ± 30 g were divided into 4 main groups. The rats were divided into 12 subgroups according to the early, middle, and late periods. A fracture model was created in rat femurs, and surgical fixation was performed. Postoperative analgesic treatment protocols included phenyramidol, diclofenac, phenyramidol + diclofenac, and the control group. The rats were sacrificed on the fifteenth, thirtieth, and forty-fifth days and were evaluated radiologically, histopathologically, and biomechanically. Scoring was conducted independently by 2 orthopedists not involved in the study. When the results were analyzed statistically, no statistically significant difference was observed between the fifteenth and thirtieth day radiology score values of the control, diclofenac, phenyramidol, and Phenyramidol + diclofenac groups (p > 0.05), but there was a statistically significant difference (p < 0.05) between the forty-fifth day radiology score values of the control, diclofenac, phenyramidol, and phenyramidol + diclofenac groups. Our study shows that the use of diclofenac or phenyramidol alone negatively affects postoperative fracture healing. However, this effect was less pronounced in the combined treatment group. Histologic examination revealed that neither treatment had a significant effect on healing. There were statistical differences in biomechanical and radiologic properties between the phenyramidol and diclofenac groups; in particular, the diclofenac group had lower biomechanical properties.

The Therapeutic Potential of Metformin for Attenuating Postsurgical Adhesion Band Formation

Objectives: Intra-abdominal adhesions are the most frequently occurring postoperative complication following abdominopelvic surgery. Peritoneal adhesion formation can lead to infertility, chronic pelvic pain, and intestinal obstruction. Several studies have shown the potential role of metformin in reducing inflammation. Here, we explored the therapeutic potency of Metformin against postsurgical adhesion band formation. Methods: We adopted Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines for the experimental protocol. Peritoneal adhesions were examined macroscopically .Metformin (100 mg/kg) was administered intraperitoneally in male albino Wistar rats. After 9 days, macroscopic evidence and score of fibrotic bands based on scaling methods were performed and evaluated by the Nair and Leach scoring system. Moreover, the anti-inflammatory and antifibrosis effects were investigated by using hematoxylin and eosin, Masson's trichrome staining, the enzyme-linked immunosorbent assay (ELISA), and reverse transcription polymerase chain reaction (RT-PCR). Results: Metformin inhibited the stabilization of adhesion bands and appeared to elicit antiinflammatory responses by attenuating submucosal edema, suppressing proinflammatory cytokines, decreasing proinflammatory cell infiltration, and inhibiting oxidative stress at the site of peritoneal surgery. We also showed that metformin prevents fibrotic adhesion band formation by reducing excessive collagen deposition and suppression of profibrotic gene expression at the peritoneum adhesion tissues via modulation of Col 1A1/A3. Conclusion: These results supported the potential application of metformin in preventing postsurgical adhesion band formation by inhibiting key pathologic responses of inflammation and fibrosis in patients post-surgery.

AGMATINE ADMINISTRATION ALLEVIATES NERVE DAMAGE AND IMPROVES NERVE FUNCTION IN METHOTREXATE INDUCED PERIPHERAL NEUROPATHY IN RATS

Objective: Chemotherapeutic agents can produce neurodegenerative changes. This study was conducted to assess the therapeutic potential of agmatine, a neuromodulator, on methotrexate induced neurodegeneration in sciatic nerve. Materials and Methods: 40 male Wistar albino rats were assigned into four groups at random as control, methotrexate, agmatine and methotrexate-agmatine. Methotrexate was injected intraperitoneally at a 37.5 mg/kg/week dose for 3 weeks. Afterwards, agmatine was administered intraperitoneally twice a day at a 40 mg/kg dose for 7 days. Sciatic functional index, nociceptive pain perception and behavioral changes were analyzed every week. Nerve conduction velocity was evaluated. Apoptotic activity and mitophagy, histopathological changes in sciatic nerves were examined. Results: Methotrexate administration resulted in a prolonged escape time to the platform and decreased the time spent in the quadrant in the water maze test; elevated nociceptive latencies; decreased the number of frames passed in the open field test; reduced sciatic NCV and SFI score. Besides, methotrexate administration caused a reduction in myelin thickness and axon diameter in sciatic nerve and a more intense glial fibrillary acidic protein immunoreactivity. Methotrexate administration triggered an increase in the Bax/Bcl-2 protein expression ratio without changing the expression level of Parkin, indicating a slight apoptotic activation. agmatine administration improved methotrexate induced changes in behavioral performances, nociceptive pain perception, nerve conduction, SFI scores and histopathological changes. Conclusion: Agmatine has been demonstrated to possess a therapeutic potential in methotrexate induced degeneration and peripheral neuropathy in the rat sciatic nerve.