Oxidative Stress and Neutrophil Function in Cats with Chronic Renal Failure

Background: Oxidative stress is an important component in the progression of chronic renal failure (CRF) and neutrophil function may be impaired by oxidative stress. Hypothesis: Cats with CRF have increased oxidative stress and decreased neutrophil function compared with control cats. Animals: Twenty cats with previously diagnosed renal failure were compared with 10 age‐matched control cats. Methods: A biochemical profile, CBC, urinalysis, antioxidant capacity, superoxide dismutase (SOD) enzyme activity, reduced to oxidized glutathione ratio (GSH : GSSG), and neutrophil phagocytosis and oxidative burst were measured. Statistical comparisons (2‐tailed t‐test) were reported as mean ± standard deviation. Results: The CRF cats had significantly higher serum blood urea nitrogen, creatinine, and phosphorus concentrations than control cats, and significantly lower PCV and urine specific gravity than control cats. The GSH : GSSG ratio was significantly higher in the CRF group (177.6 ± 197, 61.7 ± 33; P < .02) whereas the antioxidant capacity was significantly less in the CRF group (0.56 ± 0.21, 0.81 ± 0.13 Trolox units; P < .005). SOD activity was the same in control and CRF cats. Neutrophil oxidative burst after Escherichia coli phagocytosis, measured as an increase in mean fluorescence intensity, was significantly higher in CRF cats than controls (732 ± 253, 524 ± 54; P < .05). Conclusions: The higher GSH : GSSG ratio and lower antioxidant capacity in CRF cats is consistent with activation of antioxidant defense mechanisms. It remains to be determined if supplementation with antioxidants such as SOD beyond the level of control cats would be of benefit in cats with CRF.     

Antioxidant status and biomarkers of oxidative stress in cats with diabetes mellitus

Increasing evidence implicates oxidative damage in the progression and pathologic complications of human diabetics. This study assessed antioxidant status and oxidative stress in cats with diabetes mellitus (DM). Antioxidant status was measured in diabetic (n = 10) and control (n = 10) cats by HPLC of vitamin E isomers, reduced (GSH) and oxidized glutathione (GSSG), and calculation of the GSH:GSSG ratio. Biomarkers of protein, lipid and DNA peroxidation (fructosamine, isoprostanes and Comet assay, respectively), and neutrophil function evaluated oxidative stress. Correlation between glycemic control and antioxidant status/ oxidative stress was also investigated. A diabetic index was generated using clinical signs, body condition score, insulin dose, fructosamine, fasted blood glucose and urinary glucose and ketones. Alpha tocopherol was increased (DM = 0.11 μg/mL, controls = 0.06 μg/mL; p = 0.0012) and gamma tocopherol was decreased (DM = 0.03 μg/mL, controls = 0.05 μg/mL; p = 0.0065) in diabetic vs. control cats. There was no difference in the GSH:GSH ratio between groups. Predictably, fructosamine was greater in diabetic vs. control cats (DM = 447 μmol/L, controls = 204 μmol/L; p < 0.0001). Antioxidant status/oxidative stress was not associated with glycaemic control in diabetic cats. Despite strong association of DM with oxidative stress in humans, this simple relationship is not found in diabetic cats. They have both increased and decreased parameters of systemic oxidative stress compared with control cats. This may be due to higher levels of antioxidants in feline therapeutic diets, the relatively short duration of disease in cats compared with humans, or other factors.     

Oxidative stress during acute FIV infection in cats

Oxidative stress is thought to contribute to the pathogenesis of HIV infection in humans. For example, CD4(+) T cells are particularly affected in HIV patients and oxidative stress may also contribute to impairment of neutrophil function in HIV/AIDS patients. Since cats infected with FIV develop many of the same immunological abnormalites as HIV-infected humans, we investigated effects of acute FIV infection on oxidative stress in cats. Cats were infected with a pathogenic strain of FIV and viral load, changes in neutrophil number, total blood glutathione, malondiadehye, antioxidant enzyme concentrations, and reduced glutathione (GSH) concentration in leukocytes were measured sequentially during the first 16 weeks of infection. We found that superoxide dismutase and glutathione peroxidase concentrations in whole blood increased significantly during acute FIV infection. In addition, neutrophil numbers increased significantly during this time period, though their intracellular GSH concentrations did not change. In contrast, the numbers of CD4(+) T cells decreased significantly and their intracellular GSH concentration increased significantly, while intracellular GSH concentrations were unchanged in CD8(+) T cells. However, by 16 weeks of infection, many of the abnormalities in oxidative balance had stabilized or returned to pre-inoculation values. These results suggest that acute infection with FIV causes oxidative stress in cats and that CD4(+) T cells appear to be preferentially affected. Further studies are required to determine whether early treatment with anti-oxidants may help ameliorate the decline in CD4(+) T cell number and function associated with acute FIV infection in cats.     

Remission of Diabetes Mellitus in Cats with Diabetic Ketoacidosis

Background: Diabetic ketoacidosis (DKA) has long been considered a key clinical feature of type‐1 diabetes mellitus (DM) in humans although. An increasing number of cases of ketoacidosis have been reported in people with type‐2 DM. Hypothesis/Objectives: Cats initially diagnosed with DKA can achieve remission from diabetes. Cats with DKA and diabetic remission are more likely to have been administered glucocorticoids before diagnosis. Animals: Twelve cats with DKA and 7 cats with uncomplicated DM. Methods: Retrospective case review. Medical records of cats presenting with DKA or DM were evaluated. Diabetic remission was defined as being clinically unremarkable for at least 1 month after insulin withdrawal. The cats were assigned to 1 of 3 groups: (1) cats with DKA and diabetic remission; (2) cats with DKA without diabetic remission; and (3) cats with DM and diabetic remission. Results: Seven cats with DKA had remission from diabetes. These cats had significantly higher concentrations of leukocytes and segmented neutrophils, and significantly lower concentrations of eosinophils in blood and had pancreatic disease more often than did cats with uncomplicated DM and diabetic remission. With regard to pretreatment, 3/7 cats in group 1, 1/5 cats in group 2, and 1/7 cats in group 3 had been treated with glucocorticoids. Conclusions and Clinical Importance: Remission of DM in cats presenting with DKA is possible. Cats with DKA and remission have more components of a stress leucogram, pancreatic disease, and seemed to be treated more often with glucocorticoids than cats with uncomplicated DM and diabetic remission.     

Antioxidant prevention of Heinz body formation and oxidative injury in cats

OBJECTIVE: To determine the effectiveness of 3 antioxidants in preventing Heinz body anemia in cats. DESIGN: Prospective study. ANIMALS: 44 specific-pathogen-free healthy cats. PROCEDURE: Cats were housed individually, divided randomly into 4 groups, and given the following orally every 12 hours: empty gelcaps (control cats), N-acetylcysteine (NAC, 100 mg/kg of body weight), vitamin E (d,l-alpha-tocopherol; 400 IU), or ascorbate (250 mg). After 2 weeks, Heinz bodies were induced by dietary onion powder (OP; 1% or 3% of dry matter) or propylene glycol (PG, 8% wt/vol in drinking water) for an additional 3 weeks. Intake of treated water or food was recorded daily. Body weight, PCV, Heinz body and reticulocyte percentages, reduced glutathione concentration, and total antioxidant status were measured twice weekly in all cats. RESULTS: Heinz body percentage and degree of anemia did not differ significantly among cats receiving antioxidants and control cats except in cats that ingested water containing PG, in which antioxidant supplementation was associated with a decrease in water intake. Of cats that were fed a diet that contained OP, cats that received NAC had significantly higher reduced glutathione concentrations, compared with other cats in the experiment. Total antioxidant status did not consistently correlate with antioxidant supplementation or type of oxidant administered (ie, OP or PG). CONCLUSIONS AND CLINICAL RELEVANCE: Although the effect of antioxidant supplementation on Heinz body anemia in cats was minimal, antioxidants may have subclinical biochemical effects such as GSH sparing that may be important against milder forms of oxidative stress.     

高蛋白膳食对小鼠胰腺功能的氧化损伤

为探讨高蛋白膳食对小鼠胰腺功能的影响,试验选用30只C57BL/6J雄性小鼠,按体重随机分成对照组、高蛋白组和抗氧化剂组3组。试验2周后处死小鼠,取胰腺组织进行检测。结果表明,与对照组相比,高蛋白组MDA显著升高（P＜0.05）,SOD、GSH-Px活性和T-AOC显著下降（P＜0.05）,脏器中胰腺重影响较大,表现为显著增加,蛋白质、DNA和RNA浓度显著提高,消化酶活性显著降低,生长抑素和胰岛素水平显著提高（P＜0.05）。添加抗氧化剂—半胱胺后,自由基水平被降低,抗氧化能力被提高,胰腺功能也有所改善。因此,高蛋白膳食可通过破坏胰腺氧化和抗氧化平衡状态,增加自由基对胰腺内外分泌功能的氧化应激损伤。     

Effect of a bioflavonoid dietary supplement on acetaminophen-induced oxidative injury to feline erythrocytes

OBJECTIVE: To determine the effect of a commercial bioflavonoid antioxidant on acetaminophen-induced oxidative injury to feline erythrocytes. DESIGN: Randomized controlled study. ANIMALS: 45 healthy age-matched cats. PROCEDURE: Cats were assigned to 3 experimental groups. Groups 1 and 3 received a bioflavonoid antioxidant (10 mg/d) orally for 2 weeks. Groups 2 and 3 received an oxidative challenge with acetaminophen (90 mg/kg [41 mg/lb] of body weight, PO) on day 7. Packed cell volume, percentage of erythrocytes with Heinz bodies, blood methemoglobin concentration, and blood reduced and oxidized glutathione concentrations were determined at various times during the 2-week study period. RESULTS: Adverse effects were not associated with bioflavonoid antioxidant administration alone. Acetaminophen administration resulted in a significant increase in methemoglobin concentration in groups 2 and 3; differences were not detected between these groups. Heinz body concentrations in groups 2 and 3 increased after acetaminophen administration; however, the increase in cats that received the antioxidant was significantly less than in group-2 cats. Total blood glutathione concentrations did not change significantly in groups 2 and 3 after acetaminophen administration; however, ratio of reduced to oxidized glutathione concentration increased significantly after administration in group-2 cats, compared with group-3 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of bioflavonoid antioxidants to cats at risk for oxidative stress may have a beneficial effect on their ability to resist oxidative injury to erythrocytes.     

Effects of an oral superoxide dismutase enzyme supplementation on indices of oxidative stress, proviral load, and CD4:CD8 ratios in asymptomatic FIV-infected cats

This study was designed to test the effect of antioxidant supplementation on feline immunodeficiency virus (FIV)-infected felines. Six acutely FIV-infected cats (> or =16 weeks post-inoculation) were given a propriety oral superoxide dismutase (SOD) supplement (Oxstrin; Nutramax Laboratories) for 30 days. Following supplementation, the erythrocyte SOD enzyme concentration was significantly greater in the supplemented FIV-infected group than the uninfected control group or the unsupplemented FIV-infected group. The CD4+ to CD8+ ratio increased significantly (0.66-0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats. Proviral load and reduced glutathione (GSH) levels in leukocyte cell types did not change significantly following supplementation. Antioxidant supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats. This result warrants further investigation with trials of antioxidant therapy in FIV-infected cats that are showing clinical manifestations of their disease, as well as in other feline patients where oxidative stress likely contributes to disease pathogenesis, such as diabetes mellitus and chronic renal failure.     

Effects of diet on glucose control in cats with diabetes mellitus treated with twice daily insulin glargine

The purpose of this study was to evaluate the effects of dietary modification in addition to twice daily insulin glargine. Cats were treated with insulin glargine twice daily and randomized to receive either a low carbohydrate, high protein (LCHP) diet (n=6) or a control diet (n=6) for 10 weeks. Re-evaluations of clinical signs, blood glucose curves, and serum fructosamine concentrations were performed at weeks 1, 2, 4, 6, and 10. Two of 12 cats achieved complete remission by the end of the study but remission rate was not different between diet groups. Using twice daily insulin glargine and frequent monitoring, all cats in both diet groups achieved successful glycemic control. Frequent monitoring is key to achieving glycemic control in diabetic cats; potential benefits of dietary modification require further evaluation.     

Effects of dietary cysteine on blood sulfur amino acid, glutathione, and malondialdehyde concentrations in cats

OBJECTIVE: To determine effects of dietary cysteine on blood sulfur amino acids (SAA), reduced glutathione (GSH), oxidized glutathione (GSSG), and malondialdehyde (MDA) concentrations in cats. ANIMALS: 12 healthy adult cats. PROCEDURE: Cats were fed diets with a nominal (0.50 g/100 g dry matter [DM]), moderate (1.00 g/100 g DM), or high (1.50 g/100 g DM) cysteine content in a 3 X 3 Latin square design with blocks of 8 weeks' duration. Venous blood samples were collected after each diet had been fed for 4 and 8 weeks, and a CBC and serum biochemical analyses were performed; poikilocyte, reticulocyte, and Heinz body counts were determined; and MDA, GSH, GSSG, and SAA concentrations were measured. RESULTS: Blood cysteine and MDA concentrations were not significantly affected by dietary cysteine content. Blood methionine, homocysteine, and GSSG concentrations were significantly increased when cats consumed the high cysteine content diet but not when they consumed the moderate cysteine content diet, compared with concentrations obtained when cats consumed the nominal cysteine content diet. Blood GSH concentrations were significantly increased when cats consumed the moderate or high cysteine content diet. CONCLUSIONS: Increased dietary cysteine content promotes higher blood methionine, homocysteine, GSH, and GSSG concentrations in healthy cats. CLINICAL RELEVANCE: Supplemental dietary cysteine may be indicated to promote glutathione synthesis and ameliorate adverse effects of oxidative damage induced by disease or drugs.     

Effect of vitamin A and/or E on plasma enzymatic antioxidant systems and total antioxidant capacity of broiler chickens challenged with carbon tetrachloride

This study was conducted to investigate the effect of vitamin A and E supplementation on the antioxidant defences of broiler chickens against carbon tetrachloride (CCl(4))-induced oxidative stress at 4 weeks of age. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities as well as total antioxidant (TAO) level were analysed before and after CCl(4) challenge. Day-old Lohman broiler chickens (n = 144) were randomly assigned to six factorially arranged dietary treatments consisting of vitamin A [1.35 (control) or +20 mg/kg] and vitamin E [20 (control), +40 or +60 mg/kg]. The background of vitamins A and E in the basal diet was 4500 IU (1.35 mg) and 30 IU (20 mg) respectively. At 4 weeks of age, eight chickens from each treatment were bled before interperitoneal injection with 1 ml of CCl(4) (mixed with olive oil in a ratio of 1:1) and bled again 24 h post-injection. Vitamin E supplementation decreased (p < 0.05) the activity of both SOD and GPX and showed a tendency (p = 0.07) for TAO reduction. CCl(4) attenuated SOD and GPX activities as well as TAO level. The decrease was profound (p < 0.05) in chickens fed the basal diet as well as those fed basal diet supplemented with 20 mg vitamin A. TAO levels behaved similarly when chickens were challenged with CCl(4). After CCl(4) injection, SOD activities of all experimental groups were equivalent. The presence of vitamin A decreased (p < 0.05) plasma GPX activity in chickens fed the basal diet supplemented with 40 mg/kg of vitamin E. Results of this experiment suggested that vitamin E supplementation elevated antioxidant enzyme activities while vitamin A supplementation attenuated this effect. Vitamin E supplementation improved the total reducing power by maintaining comparable levels of TAO upon CCl(4) challenge. Further experiments need to be carried out to investigate the role of vitamin A in oxidative stress and to evaluate the lipid peroxidation products.     

Effects of carnitine and taurine on fatty acid metabolism and lipid accumulation in the liver of cats during weight gain and weight loss

OBJECTIVE: To determine the effects of carnitine (Ca) or taurine (Ta) supplementation on prevention of lipid accumulation in the liver of cats. ANIMALS: 24 adult cats. PROCEDURE: Cats were fed a weight-gaining diet sufficient in n-6 polyunsaturated fatty acids (PUFAs), low in long-chain n-3 PUFAs (n-3 LPUFA), and containing corn gluten for 20 weeks. Cats gained at least 30% in body weight and were assigned to 4 weight-reduction diets (6 cats/diet) for 7 to 10 weeks (control diet, control plus Ca, control plus Ta, and control plus Ca and Ta). RESULTS: Hepatic lipids accumulated significantly during weight gain and weight loss but were not altered by Ca orTa after weight loss. Carnitine significantly increased n-3 and n-6 LPUFAs in hepatic triglycerides, decreased incorporation of 13C palmitate into very-low-density lipoprotein and hepatic triglycerides, and increased plasma ketone bodies. Carnitine also significantly increased weight loss but without altering the fat to lean body mass ratio. Taurine did not significantly affect any variables. Diets low in n-3 LPUFAs predisposed cats to hepatic lipidosis during weight gain, which was further exacerbated during weight loss. Mitochondrial numbers decreased during weight gain and weight loss but were not affected by treatment. Carnitine improved fatty acid oxidation and glucose utilization during weight loss without correcting hepatic lipidosis. CONCLUSIONS AND CLINICAL RELEVANCE: The primary mechanism leading to hepatic lipidosis in cats appears to be decreased fatty acid oxidation. Carnitine may improve fatty acid oxidation but will not ameliorate hepatic lipidosis in cats fed a diet low in n-3 fatty acids.     

Comparison of a low carbohydrate-low fiber diet and a moderate carbohydrate-high fiber diet in the management of feline diabetes mellitus

This study compared the effects of a moderate carbohydrate-high fiber (MC-HF) food and a low carbohydrate-low fiber (LC-LF) food on glycemic control in cats with diabetes mellitus. Sixty-three diabetic cats (48 male castrated, 15 female spayed) were randomly assigned to be fed either a canned MC-HF (n = 32) food or a canned LC-LF (n = 31) food for 16 weeks. Owners were blinded to the type of diet fed. CBC, urinalysis, serum chemistry panel, fructosamine concentration and thyroxine concentration were determined on initial examination, and a complete blood count, serum chemistry panel, urinalysis and serum fructosamine concentration were repeated every 4 weeks for 16 weeks. Insulin doses were adjusted as needed to resolve clinical signs and lower serum fructosamine concentrations. Serum glucose (P = 0.0001) and fructosamine (P = 0.0001) concentrations significantly decreased from week 0 to week 16 in both dietary groups. By week 16, significantly more of the cats fed the LC-LF food (68%, 22/31), compared to the cats fed the MC-HF food (41%, 13/32), had reverted to a non-insulin-dependent state (P = 0.03). Cats in both groups were successfully taken off of insulin regardless of age, sex, type of insulin administered or duration of clinical disease before entering the study. There was no significant difference in the initial or final mean body weights or in the mean change in body weight from week 0 to week 16 between dietary groups. Diabetic cats in this study were significantly more likely to revert to a non-insulin-dependent state when fed the canned LC-LF food versus the MC-HF food.     

太子参茎叶对断乳仔猪抗氧化和抗应激能力的影响

试验旨在研究太子参茎叶对断乳仔猪抗氧化和抗应激能力的影响。将60头杜-长-大断乳仔猪,随机分为4组,每组3个重复,每个重复5头。空白对照组饲喂基础日粮,试验组分别在基础日粮中添加0.5%、1%和1.5%的太子参茎叶粉,分别于50日龄和70日龄采血,检测血清抗氧化和抗应激指标。结果显示,太子参茎叶添加组试验猪与空白对照组相比,血清中MDA含量显著降低,GSH-Px和SOD活性显著升高,T3、T4和皮质醇含量显著升高。结果表明,太子参茎叶能够显著提高断乳仔猪抗氧化和抗应激能力。     

大豆胰蛋白酶抑制因子对小鼠胰腺氧自由基水平的影响

为研究大豆胰蛋白酶抑制因子对小鼠胰腺氧自由基水平的影响,试验选用36只昆明种雄性小鼠,按体质量随机分为3组。第一组为对照纽,饲喂基础日粮;第二组为试验组,饲喂含有大豆胰蛋白酶抑制因子的基础日粮,第三组为抗氧化剂组,饲喂舍大豆胰蛋白酶抑制因子＋维生素C的日粮。试验期3周,空腹屠宰,眼球采血制备血清,迅速取出胰腺进行氧化和抗氧化指标检测。结果表明,大豆胰蛋白酶抑制因子能显著增加氧自由基水平。与对照组比较,试验组小鼠血清和胰腺的MDA（malondialdehyde,MDA）含量分别显著地增加了98．17％,185．58％,抗超氧阴离子自由基和抑制羟自由基能力被显著降低,TAOC、S013（superoxidedismutase）、CAT和GSH—Px活性被显著减少（P〈0．05）。添加维生素C后,氧化应激被减轻,但氧化指标仍高于对照组。上述结果表明,大豆胰蛋白酶抑制因子能够导致氧化和抗氧化不平衡,从而使其处于氧化应激状态。     

Heinz Body Formation Associated With Ketoacidosis in Diabetic Cats

Oxidative damage plays an important role in the pathophysiology of diabetes and diabetic complications. Feline hemoglobin is uniquely susceptible to oxidative denaturation; therefore, Heinz body formation is a highly sensitive indicator of in vivo oxidative stress in this species. Heinz bodies also contribute to anemia. We investigated hematological and clinical biochemical changes in 30 cats with spontaneous diabetes mellitus (as compared to 15 healthy control cats) and evaluated the relationship of these changes to erythrocyte oxidative damage. Cats were categorized as ketoacidotic or nonketoacidotic based on their clinical presentation and the presence of urine ketones. Ketoacidotic cats had significantly ( P = .0009) more Heinz bodies (28.3% ± 9.1 %) than nonketotic diabetic cats (6.5% ± 1.60%) and healthy control cats (0.6% ± 0.2%). Percent Heinz bodies in diabetic cats directly correlated with plasma β-hydroxy-butyrate concentration ( r = .622; P = .0002), as well as with serum chloride concentration ( r = -0.576; P = 0.0009) and the number of monocytes ( r = .536; P = .0023). Percent Heinz bodies were negatively correlated with erythrocyte glutathione concentrations. Erythrocyte membrane lipid peroxidation was slightly but not significantly increased in diabetic cats. There were no significant associations between percent Heinz bodies and degree of anemia, hyperglycemia, or glycohemoglobin. These data indicate that ketones are associated with oxidative hemoglobin damage in cats, and suggest that ketone metabolism, ie by cytochrome P450 2E1, may be a potential source of in vivo oxygen radical generation in animals with ketosis.     

Effects of a skullcap root supplement on haematology,serum parameters and antioxidant enzymes in rabbits on a high‐cholesterol diet

We studied the effects of Scutellaria baicalensis root on blood parameters and antioxidant enzyme activities in rabbits fed a high‐cholesterol diet. Thirty‐two New Zealand White rabbits were divided into four groups of eight animals each. They were fed a standard diet (C group), a diet with a 1% pure cholesterol supplement (CH group), a diet with a 1% pure cholesterol supplement and a 9% skullcap root supplement (CH + SR group), or a diet with a 9% skullcap root supplement (SR group). After 6 weeks, the rabbits fed the high‐cholesterol diet had significantly decreased RBC and Hb levels and significantly increased MCV, MCH and Fe levels (p ≤ 0.05). The skullcap root supplement had no adverse effects on the haematological parameters. The values for RBC, Hb, HCT, MCV, MCH and MCHC were similar in the skullcap root‐treated and control rabbits. We also observed a remarkable elevation in the serum TC, LDL and TG levels at the end of the 6‐week period. The rabbits fed the cholesterol diet showed decreased activity of the erythrocyte GSH‐Px compared with the rabbits fed the basal diet. The GSH‐Px activity was significantly higher in the rabbits fed the CH + SR diet than in those on the CH diet. The erythrocyte SOD activity was also significantly decreased in the rabbits on the CH diet. However, the CH + SR group rabbits showed significantly enhanced erythrocyte SOD activity. The SOD level in the CH + SR rabbits was 34.91 U/ml, which was a 23% increase (p ≤ 0.05) in relation to the results for the CH group and only 15% diminished in relation to the control group. These results suggest that the dietary supplementation of skullcap root may improve rabbit antioxidant systems and protect against the risks from a high‐cholesterol diet.     

骆驼乳清蛋白对热应激所致大鼠肝氧化损伤的保护作用

本试验旨在研究骆驼乳清蛋白（CWP）对热应激（HS）大鼠肝损伤、氧化应激及肝功能的保护作用。选取6周龄SD大鼠36只,适应性饲养2周后随机分为6组：正常对照组饲喂基础日粮;CWP对照组添加400 mg·kg^-1的CWP;HS组除饲喂基础日粮外,每天进行2 h HS处理,连续8 d;3个CWP干预组分别于每次HS前灌服100、200和400 mg·kg^-1的CWP。试验结束后,取大鼠肝组织,HE染色观察肝组织病理学变化,同时检测肝功能生物标志物、氧化应激标志物水平及抗氧化酶活性。结果表明：CWP降低了HS大鼠血清谷草转氨酶（AST）和谷丙转氨酶（ALT）活性,400 mg·kg^-1的CWP干预效果最好（P<0.01）;400 mg·kg^-1CWP干预组有效降低了HS诱导的大鼠肝组织病理学改变; CWP降低了大鼠肝活性氧（ROS）及丙二醛（MDA）水平,增加了超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）活性及谷胱甘肽（GSH）水平,400 mg·kg^-1的CWP干预效果最好（P<0.01）。结果提示,CWP干预能够以剂量依赖性方式降低大鼠肝氧化应激,增加抗氧化系统防御能力,从而缓解HS所致大鼠肝损伤。     

Symmetric Dimethylarginine in Cats with Hypertrophic Cardiomyopathy and Diabetes Mellitus

Background

Symmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species.

Hypothesis

Hypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM), independently of CKD, are associated with changes in serum SDMA.

Animals

Ninety‐four cats (17 with CKD, 40 with HCM, 17 with DM, and 20 healthy controls).

Methods

Case‐control study. Clinical examination, echocardiography, ECG, blood pressure, CBC, biochemistry, thyroxine, and SDMA measurement were performed. Urinalysis was performed in controls and cats with CKD and DM. Analysis of variance was used to compare overall differences in the log‐transformed SDMA data among groups. A random forest algorithm was applied to explore which clinical and other factors influenced serum SDMA.

Results

Median (range) serum SDMA for the renal group (positive control) was 19 (10–93) μg/dL, whereas for the control group (negative control), it was 10 (5–15) μg/dL. For the cardiac and diabetic groups, serum SDMA was 9 (4–24) μg/dL and 7 (3–11) μg/dL, respectively. The renal group had significantly higher SDMA concentrations and the diabetic group significantly lower SDMA concentrations compared to all other groups.

Conclusions and Clinical Importance

Serum SDMA concentrations in cats with HCM were not significantly different from those of healthy control cats. Cats with DM, however, had significantly lower SDMA concentrations than controls, a finding that needs further investigation and should be kept in mind when evaluating renal function of cats with this endocrinopathy.     

16alpha-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia: initial enhancement leading to long-term suppression

16alpha-Bromo-epiandrosterone (epiBr), a synthetic derivative of the natural hormone dehyroepiandrosterone (DHEA), was evaluated for its effects on feline immunodeficiency virus (FIV) infection in experimental cats. The rationale for this study was based on the ability of DHEA to significantly reduce the mortality to viral infections in mice. DHEA and epiBr also have demonstrable in vitro anti-viral activity for both HIV-1 and FIV. Preliminary pharmacokinetic studies in cats demonstrated that subcutaneously injected epiBr was rapidly absorbed, completely metabolized, and nontoxic. Metabolites were excreted in both urine and feces, with the latter having the most complex pattern of breakdown products. Cats were then divided into four groups; two groups were infected with FIV and two uninfected. Two groups, one infected and one uninfected were treated on 5 consecutive days of weeks 0, 4, 8, 12 and 16 with epiBr. The remaining two groups were mock treated with the drug vehicle alone. Treatment started 1 week prior to infection and extended for 4 weeks after infection. Cats were observed for 20 weeks post-FIV infection. Infected cats had identical decreases in blood neutrophil and lymphocyte counts following, regardless of whether they were treated with epiBr or vehicle alone. The CD4/CD8 T-cell ratio was decreased following FIV exposure, but was significantly more decreased for the epiBr treated animals from week 2 post-infection onward. CD4+ T cells were decreased in FIV-infected cats treated with epiBr compared to their untreated cohort, while CD8+ T cells tended to be higher in treated animals. FIV infected cats that were treated with epiBr had over one-log higher virus loads at week 2 post-infection than non-epiBr treated cohorts. In spite of this enhanced initial viremia, the subsequent levels of virus in the blood were significantly lower in epiBr treated versus untreated animals. EpiBr treated cats had significantly higher FIV-p24 antibody responses than control cats receiving vehicle alone, although primary and secondary antibody responses to a T-cell dependent non-FIV antigen, keyhole limpet hemocyanin (KLH), were unaffected. EpiBr treatment significantly decreased the expected FIV-induced suppression of IL-12 p40 mRNA levels in peripheral blood mononuclear cells (PBMCs) observed at weeks 4, 5, 8, 9 and 16 post-infection, but had no influence on FIV-induced changes in IL-4, IL-6, IL-10, IFN-gamma, MIP-1alpha and RANTES.