Laboratory Animal Research最新文献

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models.

Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis.

Conclusions: NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane generally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming 'beige' adipocytes.

Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking functional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased glycolysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of co-cultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals.

Conclusions: UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Experimental mice are often single-housed either for an individual analysis (feeding behavior, imaging, calorimetry) or as a stress paradigm (social isolation) in translational biomedical research. Reports of the influence of single housing in rodents are conflicting and may depend on age and duration of isolation. Sex is often not included as a factor. In this study we investigated the effects of 4-week single housing in male and female mice on behavior, body weight, and serum corticosterone levels.

Results: Behavioral tests showed no effect on anhedonia and stress coping, anxiety and motor exploration. Social avoidance occurred in both males and females. Regarding physiological effects, single housing did not induce changes in serum corticosterone levels, but reduced body weight gain.

Conclusions: While some mouse studies of chronic social isolation reported depression-related disturbances, our data suggest that single housing might be not necessarily be too stressful. This is important for animal welfare regulations and experiments in life science research.

Background: Maternal obesity prepregnancy, as well as gestational overweight produced by high-sucrose diet, could be evolved to the cardiometabolic diseases in offspring during adulthood. Until then, the cardiometabolic diseases were ignored that have been presented or inherited in the offspring for overnutrition were ignored, depend on gender. We proposed that maternal prepregnancy obesity in CD1 mice, as well as gestational overweight produced by a high sucrose diet, develop to cardiometabolic disease in offspring and even if gender. For detection of the cardiometabolic diseases in a Murine model with a high sucrose diet (HSD), the time series formed by the RR intervals taken from lead I of the ECG has used the corresponding Poincare plot. The heart rate variability was characterized by the standard deviation of width and length SD1, SD2 respectively of the Poincare plot and the SD1/SD2 correlation index in addition was calculated between to gender and body weight.

Results: A maternal diet was based high sucrose diet and produced overweight on progeny in both sexes, but the cardiac arrhythmias depended on gender. Other results were due to the chronic effect of high sucrose diet in offspring with this intrauterine ambiance that contributes to changes in HRV, arrhythmias, and sinus pauses, also these phenomena were observed just in the male mice offspring with high sucrose diet during adulthood.

Conclusions: We propose, that the arrhythmias originated from fetal programming due to the maternal diet in mice model and produced alterations in the offspring female more than in the male, probably due to hormones.

Background: Rheumatoid arthritis (RA) is a debilitating inflammatory disorder characterized by an overactive immune system targeting joints, leading to inflammation and intense pain. While current RA therapies effectively alleviate symptoms, they are often associated with significant side effects. This study aimed to assess the anti-inflammatory and anti-arthritic properties of an Ethanolic Extract of Myxopyrum serratulum A.W. Hill (EEMS) using animal models.

Results: The acute toxicity study with EEMS (2000 mg/kg, p.o.) on rats showed no toxicity or mortality up to the highest dose. Inflammation was induced using carrageenan, and rats were treated with varying doses of EEMS (100, 200, and 400 mg/kg, p.o.) and diclofenac to assess anti-inflammatory effects. Anti-arthritic efficacy was evaluated using Complete Freund's adjuvant (CFA)-induced inflammation, comparing EEMS to methotrexate. The results revealed dose-dependent anti-inflammatory effects of EEMS and a reversal of arthritic-induced weight loss in treated groups. Paw volume reduction was significant in both EEMS and methotrexate groups. Biochemical analyses showed elevated markers in the arthritic control group, which were normalized by EEMS and methotrexate. Notably, EEMS (400 mg/kg) significantly reduced cathepsin-D levels compared to the positive control. EEMS administration also lowered hepatic lipid peroxidation and increased endogenous antioxidants (SOD, GSH, and GPX). The 200 and 400 mg/kg doses reduced the iNOS/GADPH ratio, while the 400 mg/kg dose restored cellular and joint structure and significantly decreased IL1 levels.

Conclusions: In conclusion, EEMS demonstrated substantial protective effects, mitigating health risks associated with chronic inflammation such as arthritis. These findings underscore the ethnomedical potential of Myxopyrum serratulum as a promising anti-inflammatory and anti-arthritis agent. The study suggests that EEMS could be a viable alternative or complementary therapy for RA, offering therapeutic benefits with potentially fewer side effects than current treatments.

Ischemic heart disease is the most prevalent cause of death worldwide affecting both the gender of all age groups. The high mortality rate is due to damage of myocardial tissue that emanates at the time of myocardial ischemia and re-oxygenation, thus averting reperfusion injury is recognized as a potential way to reduce acute cardiac injury and subsequent mortality. Flavonoids are polyphenol derivatives of plant origin and empirical shreds of evidence substantiate their numerous activities such as antioxidant, anti-inflammatory, anti-apoptotic, and anti-thrombotic activity, leading to their role in cardio protection. Recent investigations have unveiled the capacity of flavonoids to impede pivotal regulatory enzymes, signaling molecules, and transcription factors that orchestrate the mediators participating in the inflammatory cascade. The present comprehensive review, dwells on the preclinical studies on the effectiveness of flavonoids from the year 2007 to 2023, for the prevention and therapeutics for myocardial ischemia-reperfusion injury.

Background: Chronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed.

Results: High fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman's capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function.

Conclusions: β-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury.