Effect of dietary antioxidants on free radical damage in dogs and cats.

Alpha-tocopherol (vitamin E) is an antioxidant that is largely involved in immune defense and enhancing the ability of biological systems to respond to oxidative stress. During the process of free radical scavenging, vitamin C supports the regeneration of vitamin E. Although the functions of antioxidants and their importance have been widely studied, the intricate interplay between antioxidants has yet to be fully elucidated, especially in dogs and cats. As such, the objective of the present study was to determine the effect of a combination of dietary antioxidants on DNA damage and antioxidant status in dogs and cats. Forty adult mixed-breed dogs and 40 adult domestic shorthair cats were randomly assigned to one of four treatment groups per species. Dogs and cats remained in these groups for the 84-d duration of the study. The food differed in antioxidant supplementation with the control food meeting all of the Association of American Feed Control Officials requirements for complete and balanced nutrition, including sufficient vitamin E to exceed the published minimum. The treatment diets were targeted to include either 500, 1,000, or 1,500 IU vitamin E/kg as well as 100 ppm of vitamin C and 1.5 ppm of ß-carotene in the food. The effect of vitamin E supplementation level on serum vitamin E concentration, DNA damage, and total antioxidant power was evaluated. Feeding diets enriched with antioxidants resulted in an increased (P < 0.05) circulating vitamin E concentration, increased (P < 0.05) immune cell protection, reduced (P < 0.05) DNA damage in dogs, and an improved (P < 0.05) antioxidant status. Overall, these data demonstrated that feeding a dry kibble with an antioxidant blend inclusive of vitamin E, vitamin C, and ß-carotene enhanced cell protection and improved antioxidant status in dogs and cats.

Animals have an impressive array of defenses to excessive reactive oxygen species in the body. The antioxidant defense system is complex and sophisticated. vitamin E, vitamin C, and ß-carotene are known to scavenge free radicals that are created during times of oxidative stress. To evaluate the effect of the various antioxidants, dogs and cats were fed one of four diets for 84 d. Diets included a control group that had vitamin E concentrations that exceeded regulatory minimums and four treatment groups that were targeted to include 500, 1,000, or 1,500 IU vitamin E/kg as well as 100 ppm of vitamin C and 1.5 ppm of ß-carotene in the food. To assess the effectiveness of the different vitamin E concentrations provided in the foods, circulating vitamin E, DNA damage, and total antioxidant power were assessed. Results from the parameters assessed showed that dogs and cats benefit from supplementing their diet with a blend of antioxidants targeted to include 100 ppm of vitamin C, 1.5 ppm of ß-carotene, and have varying benefits to increased vitamin E/kg in the food.

Data on microRNA expression, predicted gene targets and pathway analysis in response to different concentrations of a cranberry proanthocyanidin-rich extract and its metabolite 3-(4-hydroxyphenyl)-propionic acid in intestinal Caco-2BBe1 cells.

Cranberry-derived proanthocyanidin (PAC) is processed by the gut microbiota to produce 3-(4-hydroxyphenyl)-propionic acid (HPPA), among other metabolites. These data are in support of the article entitled, "Cranberry proanthocyanidin and its microbial metabolite 3,4-dihydroxyphenylacetic acid, but not 3-(4-hydroxyphenyl)-propionic acid, partially reverse pro-inflammatory microRNA responses in human intestinal epithelial cells," published in Molecular Nutrition and Food Research [1]. Here we describe data generated by nCounterⓇ Human v3 miRNA Expression Panel of RNA obtained from Caco-2BBe1 cells exposed to two different concentrations of cranberry extract rich in PAC (50 µg/ml or 100 µg/ml) or 3-(4-hydroxyphenyl)-propionic acid (5 µg/ml or 10 µg/ml) for 24 h, then stimulated with 1 ng/ml of IL-1ß or not (mock) for three hours. The raw data are publicly available at the NCBI GEO database GSE237078. This work also includes descriptive methodological procedures, treatment-responsive microRNA (miRNA) expression profiles in Caco-2BBe1 cells, and in silico mRNA gene target and pathway enrichment analyses of significantly differentially expressed miRNAs (q < 0.001). Cranberry and its components have recognized health benefits, particularly in relation to combatting inflammation and pathogenic bacterial adhesion. These data will be valuable as a reference to study the response of intestinal cells to other polyphenol-rich food sources, analyze gut microbial responses to cranberry and its metabolites in different cell lines and mammalian hosts to elucidate individualized effects, and to delineate the role of the gut microbiota in facilitating the benefits of cranberry. Moreover, these data will aid in expanding our knowledge on the mechanisms underlying the benefits of cranberry and its components.

Cranberry Proanthocyanidin and Its Microbial Metabolite 3,4-Dihydroxyphenylacetic Acid, but Not 3-(4-Hydroxyphenyl)-Propionic Acid, Partially Reverse Pro-Inflammatory microRNA Responses in Human Intestinal Epithelial Cells.

SCOPE: The molecular basis underlying the anti-inflammatory and anticarcinogenic properties of cranberries is incompletely understood. The effects of a cranberry proanthocyanidin-rich extract (PAC) and two of its gut microbial metabolites, 3,4-dihydroxyphenylacetic acid (DHPAA) and 3-(4-hydroxyphenyl)-propionic acid (HPPA), on intestinal epithelial cells microRNA (miRNA) expression and their downstream pathways at homeostasis and in inflammatory conditions, are investigated. METHODS AND RESULTS: The expression of 799 miRNAs is quantitatively assessed in differentiated Caco-2BBe1 cells pre-treated with PAC, DHPAA, or HPPA and stimulated with interleukin (IL)-1ß or not. PAC, DHPAA, and HPPA generate subsets of shared and distinct miRNA responses. At homeostasis, miRNAs affected by the metabolites, but not PAC, targeted genes enriched in kinase, Wnt, and growth factor signaling, cell growth and proliferation, apoptosis, and specific cancer pathways. In an inflammatory environment, PAC and DHPAA, but not HPPA, reverses the expression of 16 and two IL-1ß-induced miRNAs, respectively, regulating inflammatory and cancer pathways. CONCLUSION: miRNA modulation is a novel mechanism for PAC bioactivity in the gut. The gut microbiota may be necessary to unlock these effects at homeostasis and partially in inflammation.

Comparison of health parameters in normal cats fed a limited iodine prescription food vs a conventional diet.

Objectives The objective was to compare the effect on thyroid function in healthy, adult cats fed a limited-iodine food or conventional diet for 24 months. Methods Cats in the limited-iodine group (n = 14) were fed a commercial, dry food containing 0.2 ppm iodine on a dry-matter basis (DMB). Cats in the conventional diet group (n = 12) were fed an identical diet except that the iodine content was 3.2 ppm on a DMB. Both groups were maintained on their respective diets for 24 months. The median age of the cats at baseline was 3.2 years (interquartile range 2.4-4.3). Diagnostic samples were obtained for measurement of serum biochemistry parameters, thyroid hormone concentrations, complete blood count and urinalysis, and thyroid ultrasound examination was performed at baseline, 6, 12, 18 and 24 months. Results Median serum concentrations of free and total thyroxine and thyroid-stimulating hormone were within respective reference intervals for both test groups at all sampling intervals. Median urine iodine concentrations in the limited-iodine group declined significantly ( P = 0.0001) from baseline and were significantly different than conventional diet ( P ⩽0.0007). Ultrasound examination revealed no significant change in median thyroid height in the limited-iodine group at any time point. Conclusions and relevance Normal serum thyroid hormone concentrations and results of urinalysis and routine biochemical testing confirmed that the limited-iodine food was safely fed for 2 years to healthy, adult cats. Ultrasound examination showing that cats on limited-iodine did not develop a change in thyroid gland height was a further indication of the absence of iatrogenic hypothyroidism in the limited iodine diet group. These results support the lack of obvious side effects associated with feeding a limited-iodine diet for 2 years to healthy, adult cats, a situation that may occur in multi-cat households where healthy cats have access to a limited-iodine diet being used to manage cats with feline hyperthyroidism.

Positive Impact of Nutritional Interventions on Serum Symmetric Dimethylarginine and Creatinine Concentrations in Client-Owned Geriatric Cats.

A prospective study was conducted in client-owned geriatric cats to evaluate the short- term effects of a test food on serum symmetric dimethylarginine (SDMA) and creatinine (Cr) concentrations. Test food contained functional lipids (fish oil), antioxidants (vitamins C and E), L-carnitine, botanicals (vegetables), highly bioavailable protein, and amino acid supplements. Cats (n = 80) were fed either test food or owner's-choice foods (non-nutritionally controlled cohort). Cats were included based on age (≥ 9 years), indoor only, neutered, and free of chronic disease. At baseline, all cats had serum Cr concentrations within the reference interval. Renal function biomarkers and urinalysis results at baseline and after consuming test food or owner's-choice foods for 3 and 6 months were evaluated. Cats consuming test food showed significant decreases in serum Cr and BUN concentrations across time. Overall, cats consuming owner's-choice foods showed significant increases in serum SDMA concentrations at 3 and 6 months compared with baseline (P ≤ 0.05), whereas in cats consuming test food serum SDMA concentrations did not change. At baseline or during the 6-month feeding trial, 23 (28.8%) cats had increased serum SDMA, but normal serum Cr consistent with IRIS Stage 1 chronic kidney disease. This included 6 cats fed test food and 17 cats fed owner's-choice foods. In the 6 cats fed test food, serum SDMA decreased in 3 cats and remained stable in 1 cat, whereas in the 17 cats fed owner's-choice foods, serum SDMA increased in 13 cats and decreased or remained stable in 4 cats. The increase in serum SDMA concentration was significant (P = 0.02) only for cats fed owner's-choice foods. These results suggest that nonazotemic cats with elevated serum SDMA (early renal insufficiency) when fed a food designed to promote healthy aging are more likely to demonstrate stable renal function compared with cats fed owner's-choice foods. Cats fed owner's-choice foods were more likely to demonstrate progressive renal insufficiency.

Positive Impact of Nutritional Interventions on Serum Symmetric Dimethylarginine and Creatinine Concentrations in Client-Owned Geriatric Dogs.

A prospective study was conducted in client-owned geriatric dogs to evaluate the short-term effects of a test food on serum symmetric dimethylarginine (SDMA) and creatinine (Cr) concentrations. Test food contained functional lipids (fish oil), antioxidants (lipoic acid, vitamins C and E), L-carnitine, botanicals (fruits and vegetables), controlled sodium concentration, and high quality protein sources (high bioavailability and an ideal amino acid composition). Dogs (n = 210) were fed either test food or owner's-choice foods (non-nutritionally controlled cohort). Dogs were included based on age and body weight: small (6.8 to 11.4 kg) and medium dogs (11.5 to 22.7 kg) were ≥ 9 years, whereas dogs >22.7 kg were ≥ 7 years at baseline. At baseline, all dogs had to have serum Cr concentrations within the reference interval and be free of chronic disease. Renal function biomarkers and urinalysis results at baseline, and after consuming test food or owner's-choice foods for 3 and 6 months, were evaluated. Only dogs consuming test food showed significant decreases in serum SDMA and Cr concentrations (both P ≤ 0.05) across time. At baseline or during the 6-month feeding trial, 18 dogs (8.6%) had increased serum SDMA, but normal serum Cr, consistent with IRIS Stage 1 chronic kidney disease. This included 9 dogs fed test food and 9 dogs fed owner's-choice foods. Compared with baseline, after feeding 9 dogs test food for 6 months, serum SDMA decreased in 8 dogs and increased in 1 dog. After feeding 9 dogs owner's-choice foods for 6 months, serum SDMA decreased in 4 dogs and increased in 4 dogs (remained stable in 1 dog). The decreases in serum SDMA and Cr concentrations were significant (both P = 0.03) only for dogs fed test food. These results suggest that nonazotemic dogs with elevated serum SDMA (early renal insufficiency) when fed a test food designed to promote healthy aging are more likely to demonstrate improved renal function compared with dogs fed owner's-choice foods.

Comparison of foods with differing nutritional profiles for long-term management of acute nonobstructive idiopathic cystitis in cats.

OBJECTIVE: To evaluate the effect of nutrition on recurrent clinical signs of lower urinary tract (LUT) disease in cats with idiopathic cystitis. DESIGN: Randomized, controlled, masked clinical trial. ANIMALS: 31 cats with acute nonobstructive idiopathic cystitis. PROCEDURES: Cats were assigned to receive 1 of 2 foods (a cystitis prevention or control food) that differed in mineral (calcium, phosphorous, and magnesium), antioxidant, and fatty acid profiles. Owners documented LUT signs daily for up to 1 year. The primary endpoint was the number of recurrent episodes in which a cat had multiple (≥ 2 concurrent) LUT signs within a day (defined as multiple-sign day). Consecutive days in which a cat had multiple LUT signs were considered as a single episode. RESULTS: 4 cats fed prevention food and 2 cats fed control food were excluded from analysis because of noncompliance, gastrointestinal signs, food refusal, or owner voluntary withdrawal. The proportion of cats fed prevention food that had ≥ 1 recurrent episode of multiple-sign days (4/11) was not significantly lower than that of cats fed control food (9/14). However, cats fed prevention food had significantly lower mean incidence rates for recurrent episodes of multiple-sign days (0.7 episodes/1,000 cat-days) and episodes of hematuria (0.3 episodes/1,000 cat-days), dysuria (0.2 episodes/1,000 cat-days), and stranguria (0.2 episodes/1,000 cat-days) as single LUT signs, compared with cats fed control food (5.4, 3.4, 3.1, and 3.8 episodes/1,000 cat-days, respectively). Significantly fewer cats fed prevention food required analgesics (4/11), compared with cats fed control food (12/14). CONCLUSIONS AND CLINICAL RELEVANCE: Foods with differing nutritional profiles appeared to impact mean incidence rates of recurrent feline idiopathic cystitis-associated signs.

Effect of feeding a weight loss food beyond a caloric restriction period on body composition and resistance to weight gain in cats.

OBJECTIVE: To determine the effect of feeding a food with coconut oil and supplemental L-carnitine, lysine, leucine, and fiber on weight loss and maintenance in cats. DESIGN: Prospective clinical study. ANIMALS: 50 overweight cats. PROCEDURES: The study consisted of 2 trials. During trial 1, 30 cats were allocated to 3 groups (10 cats/group) to be fed a dry maintenance cat food to maintain body weight (group 1) or a dry test food at the same amount on a mass (group 2) or energy (group 3) basis as group 1. During trial 2, each of 20 cats was fed the test food and caloric intake was adjusted to maintain a weight loss rate of 1%/wk (weight loss phase). Next, each cat was fed the test food in an amount calculated to maintain the body weight achieved at the end of the weight loss phase (weight maintenance phase). Cats were weighed and underwent dual-energy x-ray absorptiometry monthly. Metabolomic data were determined before (baseline) and after each phase. RESULTS: During trial 1, cats in groups 2 and 3 lost significantly more weight than did those in group 1. During trial 2, cats lost a significant amount of body weight and fat mass but retained lean body mass during the weight loss phase and continued to lose body weight and fat mass but gained lean body mass during the weight maintenance phase. Evaluation of metabolomic data suggested that fat metabolism was improved from baseline for cats fed the test food. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that feeding overweight cats the test food caused weight loss and improvements in body condition during the weight maintenance phase, possibly because the food composition improved energy metabolism.

Effect of feeding a weight loss food beyond a caloric restriction period on body composition and resistance to weight gain in dogs.

OBJECTIVE: To determine the effect of feeding a food with coconut oil and supplemental L-carnitine, lipoic acid, lysine, leucine, and fiber on weight loss and maintenance in dogs. DESIGN: Prospective clinical study. ANIMALS: 50 overweight dogs. PROCEDURES: The study consisted of 2 trials. During trial 1, 30 dogs were allocated to 3 groups (10 dogs/group) to be fed a dry maintenance dog food to maintain body weight (group 1) or a dry test food at the same amount on a mass (group 2) or energy (group 3) basis as group 1. During trial 2, each of 20 dogs was fed the test food and caloric intake was adjusted to maintain a weight loss rate of 1% to 2%/wk (weight loss phase). Next, each dog was fed the test food in an amount calculated to maintain the body weight achieved at the end of the weight loss phase (weight maintenance phase). Dogs were weighed and underwent dual-energy x-ray absorptiometry monthly. Metabolomic data were determined before (baseline) and after each phase. RESULTS: During trial 1, dogs in groups 2 and 3 lost significantly more weight than did those in group 1. During trial 2, dogs lost a significant amount of body weight and fat mass but retained lean body mass (LBM) during the weight loss phase and continued to lose body fat but gained LBM during the weight maintenance phase. Evaluation of metabolomic data suggested that fat metabolism and LBM retention were improved from baseline for dogs fed the test food. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that feeding overweight dogs the test food caused weight loss and improvements in body condition during the weight-maintenance phase, possibly because the food composition improved energy metabolism.

Use of a novel morphometric method and body fat index system for estimation of body composition in overweight and obese dogs.

OBJECTIVE: To develop morphometric equations for prediction of body composition and create a body fat index (BFI) to estimate body fat percentage in overweight and obese dogs. DESIGN: Prospective evaluation study. ANIMALS: 83 overweight or obese dogs ≥ 1 year of age. PROCEDURES: Body condition score (BCS) was assessed on a 5-point scale, morphometric measurements were made, and visual and palpation-based assessments and dual-energy x-ray absorptiometry (DEXA) were performed. Equations for predicting lean body mass, fat mass, and body fat as a percentage of total body weight (ie, body fat percentage) on the basis of morphometric measurements were generated with best-fit statistical models. Visual and palpation-based descriptors were used to develop a BFI. Predicted values for body composition components were compared with DEXA-measured values. RESULTS: For the study population, the developed morphometric equations accounted for 98% of the variation in lean body mass and fat mass and 82% of the variation in body fat percentage. The proportion of dogs with predicted values within 10% of the DEXA values was 66 of 83 (80%) for lean body mass, 56 of 83 (68%) for fat mass, and 56 of 83 (67%) for body fat percentage. The BFI accurately predicted body fat percentage in 25 of 47 (53%) dogs, whereas the value predicted with BCS was accurate in 6 of 47 (13%) dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Morphometric measurements and the BFI appeared to be more accurate than the 5-point BCS method for estimation of body fat percentage in overweight and obese dogs. Further research is needed to assess the applicability of these findings to other populations of dogs.

Use of a morphometric method and body fat index system for estimation of body composition in overweight and obese cats.

OBJECTIVE: To develop morphometric equations for prediction of body composition and create a body fat index (BFI) system to estimate body fat percentage in overweight and obese cats. DESIGN: Prospective evaluation study. ANIMALS: 76 overweight or obese cats ≥ 1 year of age. PROCEDURES: Body condition score (BCS) was determined with a 5-point scale, morphometric measurements were made, and dual-energy x-ray absorptiometry (DEXA) was performed. Visual and palpation-based evaluation of various body regions was conducted, and results were used for development of the BFI system. Best-fit multiple regression models were used to develop equations for predicting lean body mass and fat mass from morphometric measurements. Predicted values for body composition components were compared with DEXA results. RESULTS: For the study population, prediction equations accounted for 85% of the variation in lean body mass and 98% of the variation in fat mass. Values derived from morphometric equations for fat mass and lean mass were within 10% of DEXA values for 55 of 76 (72%) and 66 of 76 (87%) cats, respectively. Body fat as a percentage of total body weight (ie, body fat percentage) predicted with the BCS and BFI was within 10% of the DEXA value for 5 of 39 (13%) and 22 of 39 (56%) cats, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The BFI system and morphometric equations were considered accurate for estimation of body composition components in overweight and obese cats of the study population and appeared to be more useful than BCS for evaluation of these patients. Further research is needed to validate the use of these methods in other feline populations.

Efficacy of two commercially available, low-magnesium, urine-acidifying dry foods for the dissolution of struvite uroliths in cats.

OBJECTIVE: To compare the efficacy and safety of using 2 commercially available, low-magnesium, urine-acidifying dry foods to dissolve sterile struvite uroliths in cats. DESIGN: Prospective, multicenter, randomized clinical trial . SAMPLE: 37 cats with presumed struvite uroliths. PROCEDURES: Cats were randomly assigned to be fed 1 of 2 low-magnesium, urine-acidifying dry foods (food A or B). For each cat, physical examination, urinalysis, and abdominal radiography were performed weekly to assess treatment response. RESULTS: 32 cats had complete urolith dissolution. Mean ± SD times for a 50% reduction in urolith size (0.69 ± 0.1 weeks) and complete urolith dissolution (13.0 ± 2.6 days) were significantly shorter for cats fed food A, compared with those (1.75 ± 0.27 weeks and 27.0 ± 2.6 days, respectively) for cats fed food B. At study termination, mean ± SD urine pH (6.083 ± 0.105) for cats fed food A was lower than that (6.431 ± 0.109) for cats fed food B. In 5 cats, uroliths did not dissolve and were subsequently determined to be composed of 100% ammonium urate (n = 4) or 100% calcium oxalate (1). Adverse events associated with diet were not observed in any of the cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dietary dissolution is safe and effective for eradication of sterile struvite uroliths in cats. Cats fed food A had faster urolith dissolution than did cats fed food B. Lack of a reduction in urolith size at 2 weeks after diet initiation was indicative of misdiagnosis or noncompliance.

Effect of antioxidant-enriched diets on glutathione redox status in tissue homogenates and mitochondria of the senescence-accelerated mouse.

The main purpose of this study was to investigate whether consumption of diets enriched in antioxidants attenuates the level of oxidative stress in the senescence-accelerated mouse (SAM). In separate and independent studies, two different dietary mixtures, one enriched with vitamin E, vitamin C, L-carnitine, and lipoic acid (Diet I) and another diet including vitamins E and C and 13 additional ingredients containing micronutrients with bioflavonoids, polyphenols, and carotenoids (Diet II), were fed for 8 and 10 months, respectively. The amounts of glutathione (GSH) and glutathione disulfides (GSSG) and GSH:GSSG ratios were determined in plasma, tissue homogenates, and mitochondria isolated from five different tissues of SAM (P8) mice. Both diets had a reductive effect in plasma; however Diet I had relatively little effect on the glutathione redox status in tissue homogenates or mitochondria. Remarkably, Diet II caused a large increase in the amount of glutathione and a marked reductive shift in glutathione redox state in mitochondria. Overall, the effects of Diet II were tissue and gender specific. Results indicated that the glutathione redox state in mitochondria and tissues can be altered by supplemental intake of a relatively complex mixture of dietary antioxidants that contains substances known to induce phase 2 enzymes, glutathione, and antioxidant defenses. Whether corresponding attenuations occur in age-associated deleterious changes in physiological functions or life span remains unknown.