Antioxidant supplementation during illness in dogs: effect on oxidative stress and outcome, an exploratory study.

OBJECTIVES: To assess whether combination antioxidant supplementation for 30 days in systemically ill dogs alters antioxidant status, degree of lipid peroxidation, clinical score and survival. MATERIALS AND METHODS: Forty client-owned systemically-ill hospitalised dogs were eligible for inclusion. Dogs were randomised to no supplementation (NS; n=19) or supplementation with N-acetylcysteine/S-adenosylmethionine/silybin and vitamin E (AS; n=20) for 30 days. Clinical score and oxidative biomarkers including glutathione, cysteine, vitamin E, selenium and urine isoprostanes/creatinine (F2 -IsoPs/Cr) were determined on days 0 and 30. Glutathione, cysteine, vitamin E and urine F2 -IsoPs/Cr were quantified by high-performance liquid chromatography, and selenium concentrations determined using atomic absorption spectroscopy. RESULTS: Thirty-two dogs completed the study (NS, n=16; AS, n=16). Vitamin E concentrations were significantly greater in the supplemented compared to the non-supplemented group. No other markers of oxidative stress significantly changed with supplementation. There was no difference in Day 30 clinical scores or survival between the two groups. CLINICAL SIGNIFICANCE: In this population of systemically-ill hospitalised dogs, combination antioxidant supplementation did not alter redox state or clinical outcome.

Serum Cobalamin and Methylmalonic Acid Concentrations in Hyperthyroid Cats Before and After Radioiodine Treatment.

BACKGROUND: Hyperthyroidism, the most common endocrine disorder in cats, has been associated with low serum cobalamin concentrations. Whether this is a functional cobalamin deficiency of clinical importance has not been assessed. HYPOTHESIS/OBJECTIVES: Cats with hyperthyroidism experience a functional cobalamin deficiency which correlates with their clinical catabolic state and is reversible with return of the euthyroid state. ANIMALS: Thirty-nine client-owned hyperthyroid cats. METHODS: Prospective observational study. Serum cobalamin, methylmalonic acid, and clinical scores were determined in each hyperthyroid cat at enrollment and when euthyroid (60 days after radioiodine treatment). RESULTS: Five of the 39 hyperthyroid cats (13%) had a low serum cobalamin concentration ranging from <150 to 290 ng/L. Serum cobalamin concentrations normalized to >350 ng/L in 2 of the hypocobalaminemic cats once euthyroid. None of the hyperthyroid/hypocobalaminemic cats had increased serum methylmalonic acid concentrations (175-601 nmol/L). In cats with clinical and biochemical hyperthyroidism, there was no correlation between serum cobalamin concentrations with total T4 concentration (P = .12) or clinical scores including body weight (P = .11) and BCS (P = .54). CONCLUSIONS AND CLINICAL IMPORTANCE: In this population of hyperthyroid cats, the prevalence of hypocobalaminemia was low. Specifically, hyperthyroid cats, in which concurrent gastrointestinal disease is unlikely. Hypocobalaminemia is not a functional deficiency requiring supplementation in hyperthyroid cats without gastrointestinal disease.

Short- and long-term cure rates of short-duration trimethoprim-sulfamethoxazole treatment in female dogs with uncomplicated bacterial cystitis.

BACKGROUND: Long-duration beta-lactam antibiotics are used for empirical treatment in female dogs with uncomplicated bacterial cystitis. However, women with bacterial cystitis are treated with short-duration potentiated sulfonamides because longer courses of beta-lactams result in lower cure and higher recurrence rates. HYPOTHESIS/OBJECTIVES: Short-duration potentiated sulfonamide treatment is more efficacious than long-duration beta-lactam treatment in achieving clinical and microbiological cures in female dogs with uncomplicated bacterial cystitis. ANIMALS: Thirty-eight client-owned female dogs. METHODS: Randomized, double-blinded, placebo-controlled clinical trial. Dogs were treated with TMP-SMX (15 mg/kg PO q12h for 3 days followed by a placebo capsule PO q12h for 7 days; Group SDS; n = 20) or cephalexin (20 mg/kg PO q12h for 10 days; Group LDBL; n = 18). Dogs were monitored for clinical and microbiological cure during treatment and at short- and long-term follow-up. RESULTS: No statistically significant differences were found between treatment groups in clinical cure rates after 3 days of treatment (89% SDS, 94% LDBL; P = 1.00) and 4 days (85% SDS, 72% LDBL; P = .44) or >30 days (50% SDS, 65% LDBL; P = .50) after conclusion of treatment or in microbiological cure rates 4 days (59% SDS, 36% LDBL; P = .44) or >30 days (44% SDS, 20% LDBL; P = .40) after conclusion of treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: We did not identify a difference in cure rates between short-duration sulfonamide and long-duration beta-lactam treatments in female dogs with uncomplicated cystitis. Long-term cure rates in both treatment groups were low. In some female dogs, "uncomplicated" bacterial cystitis may be more complicated than previously recognized.

Effect of N-acetylcysteine supplementation on intracellular glutathione, urine isoprostanes, clinical score, and survival in hospitalized ill dogs.

BACKGROUND: Antioxidant depletion and lipid peroxidation have been correlated with disease severity and associated with poor outcomes. HYPOTHESIS/OBJECTIVES: Supplementing dogs with N-acetylcysteine (NAC) during the first 48 hours of hospitalization will increase cysteine, normalize glutathione concentrations, and decrease the degree of lipid peroxidation associated with illness. ANIMALS: Sixty systemically ill hospitalized client-owned dogs and 14 healthy control dogs. METHODS: Randomized investigator-blinded, placebo-controlled prospective study. Dogs were randomized to treatment with NAC (n = 30) versus placebo (n = 30). Antioxidants, urine 8-isoprostane/creatinine (IP/Cr), and clinical score were determined before and after treatment with NAC. Glutathione, cysteine, and vitamin E concentrations were quantified using high-performance liquid chromatography. Atomic absorption spectroscopy and enzyme-linked immunosorbent assays were used to quantify selenium and isoprostane concentrations, respectively. RESULTS: Ill dogs had significantly lower vitamin E concentrations (27 versus 55 µg/mL; P = .0005) as well as elevated IP/Cr ratios (872 versus 399 pg/mg; P = .0007) versus healthy dogs. NAC supplementation significantly increased plasma cysteine (8.67 versus 15.1 µM; P < .0001) while maintaining glutathione concentrations. Dogs in the placebo group experienced a statistically significant decrease in glutathione concentrations (1.49 versus 1.44 mM; P = .0463). Illness severity and survival were unchanged after short duration NAC supplementation. CONCLUSIONS: Ill dogs experience systemic oxidative stress. Supplementation with NAC during the first 48 hours of hospitalization stabilized erythrocyte glutathione concentrations. The clinical impact of this supplementation and glutathione concentration stabilization was undetermined.

Glutathione, cysteine, and ascorbate concentrations in clinically ill dogs and cats.

BACKGROUND: Oxidative stress plays a role in the pathogenesis of many systemic diseases. Hospitalized human patients are glutathione, cysteine, and ascorbate deficient, and antioxidant depletion has been correlated with poor clinical outcome. To date little is known about antioxidant concentrations in hospitalized veterinary patients. The purpose of this study was to determine whether ascorbate, cysteine, or glutathione depletion is present in ill dogs and cats compared with healthy controls. HYPOTHESIS: Clinically ill dogs and cats would be antioxidant depleted, and depletion would correlate with illness severity and clinical outcome. ANIMALS: Clinically ill client-owned dogs (n = 61) and cats (n = 37), healthy control dogs (n = 37) and cats (n = 33). METHODS: Prospective, observational, case control study. Erythrocyte reduced glutathione, plasma cysteine, and plasma ascorbate were quantified using high-performance liquid chromatography. RESULTS: Clinically ill dogs had significantly lower erythrocyte glutathione concentrations (1.22 mM, range 0.55-3.61) compared with controls (1.91 mM, range 0.87-3.51; P = .0004), and glutathione depletion correlated with both illness severity (P = .038) and mortality (P = .010). Cats had higher ascorbate concentrations when ill (10.65 microM, range 1.13-25.26) compared with controls (3.68 microM, range 0.36-13.57; P = .0009). CONCLUSIONS AND CLINICAL IMPORTANCE: Clinically ill dogs had decreased erythrocyte glutathione concentrations, which could be a marker of illness severity and prognostic of a poor outcome. Clinically ill cats had an unexpectedly high plasma ascorbate, which could represent a unique species response to oxidative stress.