Weeks In Wistar Rats Research Articles

The association between the size of adipocyte-derived extracellular vesicles and fasting serum triglyceride-glucose index as proxy measures of adipose tissue insulin resistance in a rat model of early-stage obesity.

Obesity is a complex disease that predisposes individuals to cardiometabolic alterations. It leads to adipose tissue (AT) dysfunction, which triggers insulin resistance (IR). This suggests that people with obesity develop local IR first and systemic IR later. AT secretes extracellular vesicles, which may be physiopathologically associated with the development of IR. Our aim was to evaluate the effect of a high-fat diet on different parameters of adiposity in a rat model of early-stage obesity and to determine if these parameters are associated with markers of systemic IR. In addition, we sought to explore the relationship between fasting blood measures of IR (Triglycerides/High Density Lipoprotein-cholesterol [TAG/HDL-c] and Triglycerides-Glucose Index [TyG Index]) with the size of adipocyte-derived extracellular vesicles (adEV). We used a model of diet-induced obesity for ten weeks in Wistar rats exposed to a high-fat diet. Final weight gain was analyzed by Dual X-ray absorptiometry. Visceral obesity was measured as epididymal AT weight. IR was evaluated with fasting TyG Index & TAG/HDL-c, and adEV were isolated from mature adipocytes on ceiling culture. In the high-fat diet group, glucose and triglyceride blood concentrations were higher in comparison to the control group (Log2FC, 0.5 and 1.5 times higher, respectively). The values for TyG Index and adEV size were different between the control animals and the high-fat diet group. Multiple linear regression analyses showed that adEV size can be significantly associated with the TyG Index value, when controlling for epididymal AT weight. Our results show that lipid and glucose metabolism, as well as the size and zeta potential of adEV are already altered in early-stage obesity and that adEV size can be significantly associated with liver and systemic IR, estimated by TyG Index.

Renoprotection and Its Mechanism of Fasudil in Nitric Oxide Synthase-Deficient Hypertensive Rats

Abstract Background To investigate whether fasudil can improve renal microcirculation and protect the kidney in NG-nitro-l-arginine methyl ester (l-NAME)-induced hypertensive rats by inhibiting Rho/Rho associated coiled-coil containing protein kinase (ROCK) signal pathway. Methods The nitric oxide-deficient hypertension was induced by l-NAME (60 mg/l·d) which was provided in drinking water for 8 weeks in Wistar rats. Then they were randomly divided into l-NAME and l-NAME + fasudil groups. Blood, urine, and left kidney samples were collected after fasudil intervention for 6 weeks. Renal artery blood flow, renal function markers in serum and urine, morphological changes of renal interlobular artery, and expression levels of related proteins were detected. Results Compared with normal control rats, the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) increased while creatinine clearance (CCr) decreased in l-NAME rats. Fasudil treatment significantly decreased SCr and BUN, and increased CCr compared with l-NAME group. Compared with normal controls, the intima of renal interlobular artery increased, the lumen narrowed, the expression of ROCK-1, phosphorylated myosin phosphatase 1/myosin phosphatase 1 (p-MYPT1/MYPT1) increased while endothelial nitric oxide synthase (eNOS) protein levels decreased in l-NAME group (all P < 0.05). Fasudil treatment reduced intimal hyperplasia and lumen stenosis of renal interlobular artery, downregulated ROCK-1 and p-MYPT protein levels and upregulated eNOS expression in l-NAME rats (all P < 0.05). Conclusions Fasudil treatment improves renal function and structure of renal interlobar artery in nitric oxide-deficient hypertensive rats induced by l-NAME.

The anticonvulsant effect of chronic treatment with topiramate after pilocarpine-induced status epilepticus is accompanied by a suppression of comorbid behavioral impairments and robust neuroprotection in limbic regions in rats

Epilepsy is a widespread neurological disorder frequently associated with a lot of comorbidities. The present study aimed to evaluate the effects of the antiseizure medication topiramate (TPM) on spontaneous motor seizures, the pathogenesis of comorbid mood and cognitive impairments, hippocampal neuronal loss, and oxidative stress and inflammation in a rat model of temporal lobe epilepsy (TLE). Vehicle/TPM treatment (80 mg/kg, p.o.) was administered 3 h after the pilocarpine (pilo)-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. The chronic TPM treatment caused side effects in naïve rats, including memory disturbance, anxiety, and depressive-like responses. However, the anticonvulsant effect of this drug, administered during epileptogenesis, was accompanied by beneficial activity against comorbid behavioral impairments. The drug treatment suppressed the SE-induced neuronal damage in limbic structures, including the dorsal (CA1 and CA2 subfield), the ventral (CA1, CA2 and CA3) hippocampus, the basolateral amygdala, and the piriform cortex, while was ineffective against the surge in the oxidative stress and inflammation. Our results suggest that neuroprotection is an essential mechanism of TPM against spontaneous generalized seizures and concomitant emotional and cognitive impairments.

Macrophage Activation in the Dorsal Root Ganglion in Rats Developing Autotomy after Peripheral Nerve Injury.

Autotomy, self-mutilation of a denervated limb, is common in animals after peripheral nerve injury (PNI) and is a reliable proxy for neuropathic pain in humans. Understanding the occurrence and treatment of autotomy remains challenging. The objective of this study was to investigate the occurrence of autotomy in nude and Wistar rats and evaluate the differences in macrophage activation and fiber sensitization contributing to the understanding of autotomy behavior. Autotomy in nude and Wistar rats was observed and evaluated 6 and 12 weeks after sciatic nerve repair surgery. The numbers of macrophages and the types of neurons in the dorsal root ganglion (DRG) between the two groups were compared by immunofluorescence studies. Immunostaining of T cells in the DRG was also assessed. Nude rats engaged in autotomy with less frequency than Wistar rats. Autotomy symptoms were also relatively less severe in nude rats. Immunofluorescence studies revealed increased macrophage accumulation and activation in the DRG of Wistar rats. The percentage of NF200+ neurons was higher at 6 and 12 weeks in Wistar rats compared to nude rats, but the percentage of CGRP+ neurons did not differ between two groups. Additionally, macrophages were concentrated around NF200-labeled A fibers. At 6 and 12 weeks following PNI, CD4+ T cells were not found in the DRG of the two groups. The accumulation and activation of macrophages in the DRG may account for the increased frequency and severity of autotomy in Wistar rats. Our results also suggest that A fiber neurons in the DRG play an important role in autotomy.

Hyperleptinaemia and its Association with Postprandial Hypertriglyceridemia and Glucose Intolerance.

Introduction:Leptin resistance is believed to cause insulin resistance though the exact mechanism is not fully understood. The present study aims to investigate the temporal profile of postprandial triglyceride (PPTG) and leptin levels, and their association with each other as well as with markers of metabolic syndrome.Materials and Methods:Serum leptin and PPTG levels were measured longitudinally till 26 weeks in Wistar rats fed on controlled diet (group 1) and high sucrose diet (HSD) (group 2). Two additional groups fed on HSD were taken and treated with pioglitazone (group 3) and atorvastatin (group 4). Body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and glucose intolerance were also measured during this period. Comparison of the groups were done and Pearson's correlation coefficient was used to ascertain the association.Results:Leptin levels were significantly higher in all three groups receiving HSD compared to controlled diet group from week 2 to week 26 (P < 0.01). The postprandial triglyceride area under the curve (PPTG AUCs) were significantly higher in group 2 than controls during this period (P < 0.001). Body weight, HOMA-IR and glucose AUC were found to be significantly higher in group 2 rats than controls only from week 6, 8, and 12 respectively. In HSD-fed rats, but not in control, mean serum leptin levels from 2-26 weeks as well as peak (10th week) and 26th week were strongly associated with corresponding as well as preceding PPTG levels. Leptin levels significantly predicted HOMA-IR and prediabetes in group 2.Conclusion:This study found significant hyperleptinemia associated with postprandial hypertriglyceridemia that predicted insulin resistance and prediabetes in high sucrose diet–fed rats.

Effects of Lacosamide Treatment on Epileptogenesis, Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy.

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.

Analysis of mir-9 Expression Pattern in Rat Retina during Postnatal Development.

It is well established that miR-9 contributes to retinal neurogenesis. However, little is known about its presence and effects in the postnatal period. To expand our knowledge, miRNA-small RNA sequencing and in situ hybridization supported by RT-qPCR measurement were carried out. Mir-9 expression showed two peaks in the first three postnatal weeks in Wistar rats. The first peak was detected at postnatal Day 3 (P3) and the second at P10, then the expression gradually decreased until P21. Furthermore, we performed in silico prediction and established that miR-9 targets OneCut2 or synaptotagmin-17. Another two microRNAs (mir-135, mir-218) were found from databases which also target these proteins. They showed a similar tendency to mir-9; their lowest expression was at P7 and afterwards, they showed increase. We revealed that miR-9 is localized mainly in the inner retina. Labeling was observed in ganglion and amacrine cells. Additionally, horizontal cells were also marked. By dual miRNA-in situ hybridization/immunocytochemistry and qPCR, we revealed alterations in their temporal and spatial expression. Our results shed light on the significance of mir-9 regulation during the first three postnatal weeks in rat retina and suggest that miRNA could act on their targets in a stage-specific manner.

Prebiotic Xylo-Oligosaccharides Ameliorate High-Fat-Diet-Induced Hepatic Steatosis in Rats.

Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having only a minor impact on the GM composition. When supplemented with HFD, XOS ameliorated hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. Nuclear magnetic resonance (1H-NMR) analysis of cecal metabolites showed that, compared to the HFD, the LFD group had a healthier cecal short-chain fatty acid profile and on the HFD, XOS reduced cecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Cecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, XOS supplementation can ameliorate NAFLD by improving hepatic oxidative metabolism and affecting GM.

Oral treatment with royal jelly improves memory and presents neuroprotective effects on icv-STZ rat model of sporadic Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function. Intracerebroventricular injection of streptozotocin (icv-STZ) has been used as an experimental model of Sporadic AD (SAD) in rodents and represents a promising tool for etiopathogenic analysis and evaluation of new therapeutic proposals for AD. The icv-STZ model shows many aspects of SAD abnormalities, resulting in decreased brain glucose and energy metabolism, cognitive impairment, oxidative stress, neuronal loss, and amyloid angiopathy. Royal jelly (RJ), a substance produced by worker honeybees of the Apis mellifera species, has been popularly used for more than 30 years in areas related to health eating and natural medicine. Researches indicate that RJ has a several pharmacological activities, including neuroprotective and improvement of cognitive function. The objective of this study was to investigate the effects of oral treatment with royal jelly during 2 weeks in Wistar rats submitted to icv-STZ on a working memory and neuroprotection, as evaluated by neurogenesis, neurodegeneration and oxidative stress. In this study, icv-STZ injection induced deleterious effects in the hippocampus, associated with cognitive impairments, and developed marked neurodegeneration, besides the reduction of neurogenesis and increased oxidative stress. On the other hand, RJ long-term oral administration induced beneficial effects in animals injured by icv-STZ injection, increasing retention time for working spatial memory, reducing neurodegeneration and oxidative stress level and increasing the proliferation of new neurons in the hippocampus. Thus, RJ promotes beneficial effects on cognitive functions and exhibits a neuroprotective action in the STZ experimental model of SAD.

Hypercaloric Diet and Vitamin E Intake

PLGA (poly-lactic-co-glycolic acid) nanoparticles represent an important synthetic biocomponent that has the potential to be a promising carrier of drugs, proteins, nucleic acids, due to its biodegradability and minimal side effects. The aim of our study was to observe the antioxidant effect of vitamin E loaded in PLGA nanoparticles administered over a period of 3 weeks in Wistar rats treated with a hypercaloric diet. Glutathione (GSH) and malondiadehyde (MDA) biomarkers determined from liver lysate were analyzed to evaluate the oxidative stress (OS) induced by the hypercaloric diet. The results of our study revealed a statistically significant increase for GSH and vitamin E in group 2 of Wistar rats receiving hypercaloric diet and a daily dose of vitamin E versus group 1 (p[0.005). The antioxidant effect of vitamin E was also observed by the statistically significant decrease of MDA in group 2 of Wistar rats compared with group 1. The daily dose of vitamin E has improved the liver redox status of group 2 Wistar rats.

Effects of Fuzheng Huayu recipe on entecavir pharmacokinetics in normal and dimethylnitrosamine-induced hepatic fibrosis rats

Context Fuzheng Huayu recipe (FZHY) combined with entecavir (ETV) is used to treat the cirrhosis caused by chronic hepatitis B (CHB) infection. Objective To investigate the effect of FZHY on ETV pharmacokinetics under different conditions. Materials and methods A model of liver fibrosis was created by intraperitoneal injection of dimethylnitrosamine (DMN; 10 μg/kg) for 4 weeks in Wistar rats. Ultra-high-performance liquid chromatography–tandem mass spectrometry was used to determine the blood concentration of ETV. Pharmacokinetic characteristics of ETV (0.9 mg/kg) were investigated after co-administration with FZHY (0.55 g/kg) at certain time intervals in normal and model rats. Results The analytical method for ETV was validated at 0.5–50 μg/L with a correlation coefficient = 0.9996, lower limit of quantitation of 0.5 μg/L and mean accuracy of 104.18 ± 9.46%. Compared with the ETV-N group, the pharmacokinetic parameters of the EF-2 group did not change significantly, but that of the EF-0 group decreased in C max to 27.38 μg/L, in AUC0– t from 323.84 to 236.67 μg/h/L, and a delay in T max from 0.75 to 6.00 h; that of the EF-0 group presented a decrease in C max of 61.92%, delay in t 1/2 of 2.45 h and delay in T max of 2.92 h. The t 1/2e and V d/F of ETV were increased significantly to 8.01 h and 24.38 L/kg in the ETV-M group. Conclusions The effects of FZHY on ETV pharmacokinetics were diminished with an increase of interval time. The best time to administer both drugs is >2 h apart.

Toxicity study of ethanol extract from Oroxylumindicum (L.) Vent in rats

OBJECTIVETo evaluate the safety of Oroxylumindicum(L.) Vent extract administered for 26 weeks in Wistar rats. METHODSOroxylumindicum (L.) Vent extract was administrated to male and female rats by gavage once daily at doses of 54, 225, and450 mg • kg−1 • d−1. The rats were sacrificed after administration for13 weeks and 26 weeks. Part of the rats in each group were allowed to recover for 4 weeks after 26-week administration. Systematic examinations including haematology, urology, blood biochemistry and histomorphology were performed at the end of 13, 26 weeks of administration and 4 weeks of recovery. RESULTSNo treatment related adverse effect shappened on rats'general status, body weight, food consumption, urinary index and histomorphology examination. Although during the administration, in some rats of extract's groups, the value of Red blood cell count (RBC), white blood cell counts (WBC), hemoglobin (HGB), haematocrit (HCT) and K iron were decreased, and biochemistry index, such as glucose (GLU), triglyceride (TG), alanine transaminase (ALT) and blood urea nitrogen(BUN) were increased, the above parameters were within the normal ranges and all returned to baseline after the drug stopping for 4 weeks. CONCLUSIONThe administration of Oroxylumindicum(L.) Vent extractat levers up to 450 mg/kg (equals to 75 times of clinical dose) is well tolerated-for both genders without significant toxicity within the administration duration in this study.

Chronic agomelatine treatment prevents comorbid depression in the post-status epilepticus model of acquired epilepsy through suppression of inflammatory signaling

Inflammatory signal molecules are suggested to be involved in the mechanism underlying comorbid depression in epilepsy. In the present study, we tested the hypothesis that the novel antidepressant agomelatine, a potent melatonin MT1 and MT2 receptor agonist and serotonin 5HT2C receptor antagonist, can prevent depressive symptoms developed during the chronic epileptic phase by suppressing an inflammatory response. Chronic treatment with agomelatine (40 mg/kg, i.p.) was initiated an hour after the kainate acid (KA)-induced status epilepticus (SE) and maintained for a period of 10 weeks in Wistar rats. Registration of spontaneous motor seizures was performed through a video (24 h/day) and EEG monitoring. Antidepressant activity of agomelatine was explored in the splash test, sucrose preference test (SPT) and forced swimming test (FST) while anxiolytic effect was observed through the novelty suppression-feeding test (NSFT) during chronic phase in epileptic rats. The frequency of motor seizures detected by video and EEG recording did not differ between vehicle and Ago group. Rats with registered spontaneous motor seizures showed symptoms typical for depressive behavior that included decreased grooming, anhedonia during the dark period and hopeless-like behavior. Epileptic rats exhibited also anxiety with novelty-induced hypophagia. This behavioral deficit correlated with increased signal markers of inflammation (plasma levels of interleukin (IL)-1β and activated glia in brain), while plasma corticosterone levels were not changed. Agomelatine treatment during epileptogenesis exerted a clear antidepressant effect by suppressing all behavioral hallmarks, reducing plasma IL-1β levels and preventing microgliosis and astrogliosis in specific limbic regions. The present results suggest that agomelatine treatment starting after SE can provide an effective therapy of comorbid depression in chronic epileptic condition through suppression of inflammatory signaling.

Diacylglycerol (DAG) rich rice bran and sunflower oils modulate lipid profile and cardiovascular risk factors in Wistar rats

Diacylglycerol (DAG) oil is suggested to have anti-obesity effect in view of its distinct metabolic fate and fat oxidation. In the present investigation, dietary feeding of DAG rich sunflower and rice bran oils for 12 weeks in Wistar rats significantly decreased triacylglycerol (TAG), total cholesterol and LDL-cholesterol in serum, liver and adipose. Fat accumulation was decreased in DAG fed groups. Fecal cholesterol levels increased in DAG fed rats. DAG rich oil decreased selected cardiovascular disease (CVD) risk factors such as serum C-reactive protein (C-RP), tumor necrosis factor-alpha (TNF-α), platelet aggregation and expression of thoracic aortic proteins such as inducible nitric oxide synthase (i-NOS), cyclooxygenase-2 (COX-2), and vascular cell adhesion molecule-1 (VCAM-1) compared to TAG oil fed group. Serum clinical enzyme activity and histopathological observations of liver conforms safety of DAG oil. Thus, DAG rich oil has beneficial metabolic effects by decreasing fat accumulation, lipid profile and CVD risk factors.

In Vitro and In Vivo Biocompatibility Evaluation of Polyallylamine and Macromolecular Heparin Conjugates Modified Alginate Microbeads

Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.

Regulation effect of Aspirin Eugenol Ester on blood lipids in Wistar rats with hyperlipidemia.

BackgroundAspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with less side effects. The experiment will be conducted to investigate the efficacy of AEE on curing hyperlipidemia in Wistar rats. The rats were fed with high fat diet (HFD) for 8 weeks to induce hyperlipidemia.ResultsCompared with the model group, the results showed that AEE at 54 mg/kg dosage could significantly decrease the hyperlipidemia indexes including triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TCH) (p < 0.01), increase high density lipoprotein (HDL) (p < 0.05) for five weeks drug administration. Meanwhile, simvastatin had same effect on hyperlipidemia indexes such as TG, LDL, TC, but no significant increase in HDL.ConclusionAEE was effective against hyperlipidemia and had better anti-hyperlipidemic effect than its component, acetylsalicylic acid (Aspirin, ASA), eugenol and integration of ASA and eugenol. Under the experimental circumstance, the optimal dose of AEE to cure hyperlipidemia is 54 mg/kg for five weeks in Wistar rats.

Fructose feeding changes taurine homeostasis in wistar rats.

High-fructose intake has been shown to induce dyslipidemia and other hallmarks of the metabolic syndrome and taurine seems able to ameliorate these effects. However, the effects of high fructose intake on taurine homeostasis are currently unknown. Here we examined the effects of a high-fructose diet with or without oral taurine supplementation (2 % in drinking water) for 6 weeks in Wistar rats.

Fast food diet with CCl4 micro-dose induced hepatic-fibrosis--a novel animal model.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is defined as a spectrum of conditions ranging from hepatocellular steatosis to steatohepatitis and fibrosis, progressing to cirrhosis, which occur in the absence of excessive alcohol use. Several animal models capture aspects of NAFLD but are limited either in their representation of the disease stages or use for development of therapeutics due to the extended periods of time required to develop full histological features.MethodsHere, we report the development of a novel rat model for NAFLD that addresses some of these limitations. We used a fast food diet (FFD) and a CCl4 micro dose (0.5 ml/kg B.wt) for 8 weeks in Wistar rats. Serological analyses, gene expression profiling and liver histology studies were conducted to investigate the development of steatosis, steatohepatitis and fibrosis in the FFD-CCl4 model when compared to the individual effects of a FFD or a micro dose of CCl4 in rats.ResultsThe serum biochemical profile of the FFD-CCl4 model showed an increase in liver injury and fibrosis. This was also accompanied by a significant increase in liver triglycerides (TG), inflammation and oxidative stress. Importantly, we observed extensive fibrosis confirmed by: i) increased gene expression of fibrosis markers and, ii) moderate to severe collagen deposition seen as perisinusoidal and bridging fibrosis using H&E, Trichome and Sirius Red staining.ConclusionsIn summary, we find that the FFD-CCl4 rat model developed NAFLD histological features including, steatosis, inflammation and fibrosis in 8 weeks showing promise as a model that can be used to develop NAFLD therapeutics and liver anti-fibrotics.

Gingival vascular functions are altered in type 2 diabetes mellitus model and/or periodontitis model

The association of vascular reactivity between diabetes and periodontal disease has not been clarified. Gingival blood flow was measured by laser Doppler flowmetry for 31 weeks in Wistar rats, Wistar rats orally challenged with Porphyromonas gingivalis (Wistar rats + Porphyromonas gingivalis), Goto-Kakizaki rats, and Goto-Kakizaki rats orally challenged with Porphyromonas gingivalis (Goto-Kakizaki rats + Porphyromonas gingivalis). Effects of alveolar bone resorption on periodontal tissue was enhanced in Wistar rats + Porphyromonas gingivalis, and Goto-Kakizaki rats, with this effect being significantly enhanced by Goto-Kakizaki rats + Porphyromonas gingivalis. Using the L-band electron spin resonance technique, we succeeded in measuring oxidative stress as decay rate constant (K1 and K2) of 3-carbamoyl-2,2,5,5-tetramethylpyrrolidin-1-yloxy in the oral and maxillofacial region of the animal models. The decay rate constant (K1) of 3-carbamoyl-2,2,5,5-tetramethylpyrrolidin-1-yloxy was significantly greater in the oral and maxillofacial region of Goto-Kakizaki rats + Porphyromonas gingivalis compared to Wistar rats, Wistar rats + Porphyromonas gingivalis and Goto-Kakizaki rats groups. Gingival reactive hyperemia was attenuated by periodontal disease, and this effect was also remarkable in the diabetes mellitus model. Taken together, we found that vascular endothelial function was decreased in diabetes mellitus and/or periodontal disease animal models due to increasing oxidative stress in the gingival circulation.

Short-term treatment with a beta-blocker with vasodilative capacities improves intrarenal endothelial function in experimental renal failure

Aims In patients with renal disease the cardiovascular risk is greatly increased, and endothelial dysfunction is assumed to play a pivotal role in this process. Therefore we compared treatment effects of a beta-blocker with additional vasodilatory capacities (nebivolol) and a beta-blocker lacking these actions (metoprolol) on intrarenal and coronary vascular function in a rat model of renal failure with hypertension. Main methods Renal failure was induced by 5/6-nephrectomy (Nx) and analyzed after 4 weeks in Wistar rats. Untreated Nx, Nx/nebivolol 6 mg/d (Nx-Nebi); Nx/metoprolol 60 mg/d (Nx-Meto) and sham-operated (Sham) animals were studied. Isolated small renal and coronary arteries were investigated for endothelium-dependent relaxation to acetylcholine (ACh) and for the contribution of the endothelial mediators NO and endothelium-derived hyperpolarizing factor (EDHF). Key findings Systolic blood pressure (SBP) was significantly increased in Nx, Nx-Nebi, and Nx-Meto (168 ± 5, 153 ± 3, and 162 ± 6 mmHg) compared to Sham (138 ± 3 mmHg, p < 0.05, respectively). The increase in albuminuria of Nx (120-fold vs. Sham, p < 0.0001) was almost (− 85%) normalized by nebivolol compared to Sham ( p < 0.05), whereas metoprolol induced no significant effect. Renal arteries showed significantly increased Ach-relaxation in Nx and Nx-Nebi (Emax 86 ± 4% and 76 ± 7%, p < 0.05) due to an increase in EDHF-mediated dilation (Emax_EDHF 78 ± 7% and 73 ± 6%) compared to Sham (Emax 54 ± 4% and Emax_EDHF 44 ± 6%) and Nx-Meto (Emax 42 ± 12% and Emax_EDHF 18 ± 5%). ACh-relaxation in coronary arteries was similar between groups but the contribution of NO (relative to EDHF) was strongly increased by nebivolol. Significance The present findings offer an explanation of the nephroprotective effect of intrarenal endothelial function in renal failure.