P2X7 receptor antagonist A-438079 alleviates oxidative stress of lung in LPS-induced septic rats.

Sepsis is a deadly systemic inflammatory response of the body against infection resulting in immune response, cell differentiation and organ damage. Endotoxemia is one of the causes of sepsis-related acute respiratory distress and respiratory burst is an important generator of oxidants. Inflammation may be aggravated by overexpression of ATP-gated purinergic receptors (i.e., P2X7R) following cell damage. We aimed to evaluate the effects of P2X7R antagonist A-438079 on lung oxidative status and the receptor expression in endotoxemia of sepsis. Rats were subjected to sepsis by E. coli lipopolysaccharide (LPS) and treated with 15 mg/kg A-438079. The increase in circulatory IL-1ß and IL-8 concentrations in LPS group confirmed the systemic inflammatory response to endotoxemia compared with Control groups (p < 0.001). Besides, there was an increase in P2X7R expression in lung tissue after LPS administration. Compared with Control groups, there were significant increases in the values of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) (p < 0.001), and myeloperoxidase (MPO) (p < 0.05) in lung tissue of LPS group. P2X7R expression in lung and IL-1ß level in blood did not increase in LPS + A-438079 group. A-438079 decreased the lung levels of MDA, GSH, CAT and SOD (p < 0.001), and MPO (p < 0.01) in septic rats. As a result, administration of pathogen-associated LPS led to increased P2X7R expression into lung tissue and elevated lipid peroxidation product MDA with regard to oxidative damage. The P2X7R antagonist A-438079 alleviated the oxidative stress of lung with a balance of tissue oxidant/antioxidant factors in experimental sepsis in rats.

Protective effect of naringin against oxaliplatin-induced peripheral neuropathy in rats: A behavioral and molecular study.

Oxaliplatin (OXL) is a chemotherapeutic drug used for metastatic and other types of cancer, but it causes peripheral neuropathy as a dose-limiting side effect. Herein, we used the rat model of OXL-induced peripheral neuropathy to demonstrate the protective effects of naringin (NRG) in this neuropathy. In this study, rats were injected with OXL (4 mg/kg, body weight, i.p.) in 5% glucose solution 30 min after oral administration of NRG (50 and 100 mg/kg, body weight) on the 1st, 2nd, 5th, and 6th days. OXL caused sensory and motor neuropathy (as revealed by the hot plate, tail flick, rota-rod, and cold hyperalgesia tests) in the sciatic nerve of rats. Coadministration of oral NRG alleviated OXL-induced sensory and motor neuropathy. Levels of superoxide dismutase, catalase, glutathione peroxidase, nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, nuclear factor-κ B, tumor necrosis factor-α, interleukin-1ß, Bax, Bcl-2, caspase-3, paraoxonase, mitogen-activated protein kinase 14, neuronal nitric oxide synthase (nNOS), acetylcholinesterase, and arginase 2 in the sciatic nerve tissues were assessed by real-time polymerase chain reaction. Moreover, the protein levels of caspase-3, Bax, Bcl-2, intercellular adhesion molecules-1, glial fibrillary acidic protein, and nNOS were examined by Western blot analysis. NRG treatment significantly improved all the above-mentioned parameters and reduced OXL-induced oxidative stress, inflammation, and apoptosis in the sciatic nerve tissue. In conclusion, this study demonstrated that NRG significantly attenuated OXL-induced peripheral neuropathy and might be considered as a new protective agent to prevent the OXL-induced peripheral neuropathy.

Effects of Slaughter Age of Holstein Friesian Bulls on Meat Quality: Chemical Composition, Textural Characteristics, Sensory Attributes and Fatty Acid Profile.

This study aimed to investigate the effects of slaughter age (young vs. old), muscle type (Longissimus dorsi (LD), Gluteus medius (GM)) and fat deposits (kidney knob and channel fat, subcutaneous fat, intramuscular fat) on chemical, organoleptic, textural characteristics and fatty acid composition of Holstein Friesian bull meat. For this purpose, the carcasses of 26 Holstein Friesian bulls that had been fattened on the same private farm were assigned to two experimental groups based on their age at slaughter: a young group (YG) (average age: 17.0 ± 1.0 months old) and an old group (OG) (average age: 22.0 ± 1.0 months old). The percentage of crude protein, panel tenderness score, polyunsaturated fatty acid (PUFA) and saturated fatty acid (SFA) content, the PUFA/SFA ratio and the hypocholesterolemic fatty acid (DFA)/hypercholesterolemic fatty acid (OFA) ratio of the bull carcasses decreased significantly with increasing slaughter age. By contrast, the OFA content of the carcasses significantly increased (p < 0.05) with increasing slaughter age. Advanced slaughter age resulted in lower panel tenderness scores. Additionally, the meat of the bulls in the OG was considered to be less healthy because of the less desirable fatty acid composition and nutritional indices, such as the PUFA/SFA and hypocholesterolemic/hypercholesterolemic ratios, compared to the meat from the bulls in the YG. Furthermore, the intramuscular fat and internal fat contained high percentages of PUFA and SFA and high PUFA/SFA and hypocholesterolemic/hypercholesterolemic ratios. Interestingly, the percentage of OFA content in the internal and intramuscular fat tissues decreased with increasing slaughter age. In conclusion, this study provided evidence that slaughter age and muscle and fat type are essential sources of variations in the textural characteristics, sensory panel attributes and fatty acid profile of meat from Holstein Friesian bulls.

Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases.

BACKGROUND: Achilles tendinopathy, seen in athletes and manual labor workers, is an inflammatory condition characterized by chronic tendon pain. Owing to the toxicity that develops in various organs attributed to the use of anti-inflammatory drugs, there is a need for new therapeutic agents. PURPOSE: In the present study, the effects of quercetin (Que), the one that attracted the most attention of researchers studying this group of flavonoids, were investigated against collagenase-induced tendinopathy. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 35 Sprague-Dawley rats were used in the study. Tendinopathy was created by injecting a single dose of collagenase (10 µL; 10 mg/mL) into the tendons of rats. Thirty minutes after the injection, Que was administered at doses of 25 or 50 mg/kg. Que administration was carried out for 7 days. Animals underwent a motility test at the end of the study. In addition, markers of oxidative stress, inflammation, apoptosis, and autophagy, as well as the expression levels of matrix metalloproteinases (MMPs 2, 3, 9, and 13), ICAM-1, and STAT3, were measured in tendon tissues with biochemical, molecular, and Western blot techniques. RESULTS: The results showed that oxidative stress, inflammation, apoptosis, and autophagy were triggered by the injection of collagenase. In addition, MMPs, ICAM-1, and STAT3 were activated to participate in the development of tendinopathy. Que was found to reduce ICAM-1 levels in tendon tissue. Moreover, Que showed antioxidant, anti-inflammatory, antiapoptotic, and antiautophagic effects on tendons against tendinopathy. More important, Que suppressed the expression of MMPs in the tendon tissues. CONCLUSION: Que has protective properties against collagenase-induced tendon damage in rats. CLINICAL RELEVANCE: We believe that with further study, Que may be shown to be an alternative treatment option for athletes or others who experience tendon injuries.

Investigation of the anti-inflammatory effects of caffeic acid phenethyl ester in a model of λ-Carrageenan-induced paw edema in rats.

In the present study, it is aimed to evaluate the effects of caffeic acid phenethyl ester (CAPE) against acute paw inflammation induced by carragenan (Carr) at macro and micro levels. Therefore, in this study, 1 hour after administering intraperitoneal of indomethacin (Ind) or CAPE (10 and 30 mg/kg body weight) to Sprague Dawley rats, Carr was injected intraplantarly into their right paws. The paw volumes of the rats were measured with a plethysmometer until the 4th hour. Also, X-ray and thermal camera images were taken to determine edema and temperature changes. At the end of the study, after the paw tissues and serums were taken, oxidative stress and inflammation status were determined using biochemical, molecular, and western blot techniques. In addition, lipid and protein profiles in paw tissue were determined using HPTLC and electrophoresis methods. The results depicted that a high dose of CAPE against Carr-induced inflammation may be almost as effective as Ind used as reference.

The protective effects of hesperidin against paclitaxel-induced peripheral neuropathy in rats.

Paclitaxel (PTX), which is widely used in the treatment of solid tumors, leads to dose limitation because it causes peripheral neuropathy. This study was conducted to evaluate the potential effects of hesperidin (HES), which has various biological and pharmacological properties, against PTX-induced sciatic nerve damage. For this purpose, Sprague Dawley rats were given PTX 2 mg/kg/b.w for 5 days, then 100 or 200 mg/kg/b.w HES for 10 days, and behavioral tests were conducted at the end of the experiment. The data obtained show that PTX-induced MDA, NF-κB, IL-1ß, TNF-α, COX-2, nNOS, JAK2, STAT3, and GFAP levels decreased with HES administration. Moreover, it was observed that SOD, CAT, and GPx activities inhibited by PTX increased with HES administration. It was determined that PTX caused apoptosis in the sciatic nerve by increasing Caspase-3 and Bax levels and suppressing Bcl-2 levels. HES, on the other hand, showed an anti-apoptotic effect, increasing Bcl-2 levels and decreasing Caspase-3 and Bax levels. Also, it was observed that PTX could cause endoplasmic reticulum stress (ERS) by increasing PERK, IRE1, ATF-6, GRP78 and CHOP mRNA transcript levels, while HES could alleviate ERS by suppressing them. The results indicate that neuropathic pain associated with PTX-induced peripheral neuropathy can be alleviated by HES administration and that it is a promising compound for cancer patients. In addition, it is thought that the results of the present study contain information that will shed light for researchers regarding further studies to be conducted with HES.

Serum levels of nesfatin-1 and irisin in obese children.

Along with the developing technology in the modern age, physical activity had decreased considerably in children and adolescents alike with a concomittant and rapid increase in the prevalence of childhood obsesity. The purpose of the present study is to measure the levels of serum nesfatin-1 and irisin in obese children. The present study was carried out with a total of 62 children, including 32 obese children diagnosed between June 2017 and October 2017 and 30 healthy children. Serum nesfatin-1, irisin, SOD, MDA, fasting blood glucose, total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, aspartate amino transferase (AST), alanine amino transferase (ALT)), blood urea nitrogen (BUN), C-reactive protein (CRP), calcium (Ca), sodium (Na), potassium (P), chromium (Cr), ferritin, and vitamin B12 data were collected for each patient. In our study, mean nesfatin-1 and SOD values of the obesity group were lower than those of the control group (p <0.05, p <0.001), whereas irisin and MDA values were higher than those of the control group (p <0.001). Childhood obesity is still a significant global problem, despite increased social awareness and numerous preventive healthcare interventions. We believe that all the prospective studies to be carried out to evaluate the relationship between obesity-irisin-nesfatin-1 triad, will make positive contributions to treatment of obesity.

The diagnostic value of two commercially available human cTnI assays in goat kids with myocarditis.

BACKGROUND: Cardiac troponin I (cTnI) is a peripheral blood marker for myocardial damage. Because of the unavailability of goat-specific cTnI assays human cTnI assays may be validated for detection of myocarditis in goat kids. OBJECTIVES: The purpose of the study was to evaluate 2 commercially available human cTnI assays in goat kids with myocardial damage, and to determine the cTnI expression in cardiac muscle. MATERIALS AND METHODS: Plasma cTnI concentrations were measured in healthy goat kids (n = 7) and goat kids with myocardial damage (n = 8) using the Beckman Coulter Access Accu TnI and the Biomérieux Vidas Ultra. The results were correlated with gross necropsy and histopathologic findings, and cTnI immunhistochemistry in cardiac tissue. RESULTS: Macro- and microscopic findings confirmed myocardial damage in the myocarditis group. Mean plasma cTnI concentration was significantly higher in the myocarditis group than in the healthy control group (104.82 vs 0.02 ng/mL). The overall mean plasma cTnI concentration measured by Biomérieux Vidas Ultra (61.75 ng/mL, 95% CI: 19.55-103.95) was comparable to the mean measured by Beckman Coulter Access Accu TnI (50.08 ng/mL, 95% CI: 24.11-76.06), and cTnI concentrations measured by these assays were highly correlated (r = .977) with a -6.2% bias. Both assays were precise and accurate. CONCLUSION: The human-specific Beckman Coulter Access Accu TnI and the Biomérieux Vidas Ultra can be used for diagnostic confirmation of myocardial damage in caprine medicine.

Reliability of the Lactate Scout point-of-care instrument for the determination of blood L-lactate concentration in sheep.

BACKGROUND: Data on accuracy and precision of the Lactate Scout point-of-care (POC) analyzer in ovine medicine are lacking. OBJECTIVE: The purpose of the study was to assess the reliability of the Lactate Scout in sheep. MATERIALS AND METHODS: Fifty-seven sheep at varying ages with various diseases were included. Blood lactate concentration in samples collected from the jugular vein was measured immediately on the Lactate Scout. Plasma L-lactate concentration was measured by the Cobas autoanalyzer as the reference method. Data were subjected to Student's t-test, Passing-Bablok regression, and Bland-Altman plot analyses for comparison and assessment of accuracy, precision, and reliability. RESULTS: Plasma l-lactate concentration was consistently lower than blood L-lactate concentration (3.06 ± 0.24 vs 3.3 ± 0.3 mmol/L, P < .0001). There was a positive correlation between plasma and blood L-lactate concentrations (r = .98, P < .0001). The Lactate Scout had 99% accuracy and 98% precision with the reference method. Blood (Y) and plasma (X) L-lactate concentrations were fitted to Y = 0.28 + 1.00 · X, with a residual standard deviation of 0.31 and a negligible deviation from the identity line (P = .93). The bias was fitted to Y = 0.10 + 0.05 · X, with Sy.x of 0.44 (P < .07). CONCLUSIONS: The Lactate Scout has high accuracy and precision, with a negligible bias. It is a reliable POC analyzer to assess L-lactate concentration in ovine medicine.

Excretion rate and composition of skin surface lipids on the foreheads of adult males with type IV hyperlipoproteinemia.

OBJECTIVES: Most of the lipids of the skin surface come from sebaceous glands secretions, called sebum. Some of the sebum lipids are synthesized by sebaceous cells while some are reportedly derived from the plasma. Role of blood lipoproteins in sebum secretion rate and composition is unclear. To this end, excretion rate and composition of skin surface lipids of normo- and type IV hyperlipoproteinemic subjects were compared. DESIGN AND METHODS: Quantitative analysis of skin surface lipids was performed by three successive sampling on left, middle, and right zones of the forehead with a sebumeter. Skin surface lipid samples for the compositional analysis were collected from the forehead, extracted into n-hexane, and analyzed by high performance thin layer chromatography (HPTLC). HPTLC plates were scanned with a densitometer for the quantification of the lipids. RESULTS: Skin surface lipids from type IV hyperlipoproteinemic subjects contained higher proportion of wax ester + cholesterol ester compared with that from normolipoproteinemic subjects. However, skin surface lipid excretion rates of normo- and hyperlipoproteinemic subjects were found to be similar. CONCLUSIONS: Plasma lipid/lipoprotein concentration may be a determinant factor in sebum lipid composition.

Physiological profile of juvenile rats: effects of cage size and cage density.

Although there is a general consensus that housing conditions affect the well-being of laboratory animals, the ideal cage size and density for housing laboratory rodents has not been established. The authors investigated the effects of cage size and cage density on growth, organ development, metabolic profile, and hemogram in juvenile Sprague-Dawley rats. Larger cages and increased cage density were associated with depressions in body weight and in the weights of several organs. In general, increasing group size and density correlated more strongly with detrimental effects on the growth of females than males, although hemogram values indicated that males are more prone to emotional stress and immune suppression than females in response to increasing group size and crowding.

Hydrophobic nature of rat lymph chylomicrons.

BACKGROUND: A typical molecular structure of a lipoprotein is composed of hydrophobic lipids at the core and hydrophilic apolipoprotein side chains and lipid head groups at the surface. Some of the hydrophobic characteristics of rat lymph chylomicrons were investigated. METHODS: Thoracic duct was cannulated and lymph was collected overnight. Chylomicrons (>100 nm) were isolated by ultracentrifugation at 4 x 10(6)xg min. Since particle aggregation is a characteristic of hydrophobic nature of lipoproteins, as an index of aggregation, the turbidity generated by vortexing and storage of chylomicrons was measured spectrophotometrically at 680 nm. We also assessed the ability of chylomicrons to interact with five different hydrophobic interaction chromatography (HIC) media. RESULTS: Neither shaking nor prolonged storage at 4 degrees C produced an increase in the optical density of chylomicron solution indicating no aggregation took place. Typical elution profiles of chylomicrons through octyl, phenyl (high substance) and butyl sepharose columns showed two peaks. Peak I material emerged with 4 mol/l NaCl in a position corresponding to the void volume and peak II material eluted with water. Phenyl sepharose (high performance) media exhibited the maximum binding strength towards chylomicrons among the five different media. In the case of phenyl sepharose (low substance) column, an additional material was eluted with 3 mol/l NaCl between peaks I and II. These results indicate the heterogeneity of chylomicron surface hydrophobicity. CONCLUSION: Since particle aggregation is a characteristics of hydrophobicity of lipoproteins and believed to be an underlying cause of atherosclerosis, fractionation of lipoproteins by hydrophobic interaction chromatography may introduce a new approach into the assessment of lipoprotein atherogeneicity.