Prophylactic effects of ellagic acid and rosmarinic acid on doxorubicin-induced neurotoxicity in rats.

Doxorubicin (DOX) is a chemotherapeutic agent widely used in human malignancies. Its long-term use cause neurobiological side effects. The aim of the present study was to investigate the prophylactic effect exerted by daily administration of ellagic acid (EA) and rosmarinic acid (RA) on DOX-induced neurotoxicity in rats. Our data showed that DOX-induced significant elevation of brain malondialdehyde, tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), caspase-3, and cholinesterase associated with significant reduction in reduced glutathione, monoamines namely serotonin, dopamine, as well as norepinephrine. Concomitant administration of EA (10 mg/kg/day, p.o. for 14 days) and/or RA (75 mg/kg/day, p.o. for 14 days) with DOX significantly mitigated the neural changes induced by DOX. Meanwhile, treatment ameliorated pro-inflammatory cytokines as TNF-α, iNOS, and attenuated oxidative stress biomarkers as well as brain monoamines. In conclusion, EA and RA can effectively protect against DOX-induced neurotoxicity, and the mechanisms underlying the neuroprotective effect are potentially associated with its antioxidant, anti-inflammatory, and antiapoptotic properties.

Ellagic acid and rosmarinic acid attenuate doxorubicin-induced testicular injury in rats.

The anticancer drug doxorubicin causes testicular toxicity as an undesirable effect. The present study was undertaken to investigate the possible protection of ellagic acid and rosmarinic acid during doxorubicin administration. For this purpose eight groups of male Sprague-Dawley rats were used (n = 10), one group received vehicle served as control, and other groups received 5 mg/kg doxorubicin twice a week for 2 weeks for a cumulative dose of 20 mg/kg, ellagic acid (10 mg/kg/day, 14 consecutive days p.o.), rosmarinic acid (75 mg/kg/day, 14 consecutive days p.o.), ellagic acid and rosmarinic acid. The latter three regimens were given to control and doxorubicin-received rats. Doxorubicin decreased testicular relative weight, sperm count, motility, serum testosterone, testicular glycogen, and sialic acid with increased incidence of histopathological changes, oxidative stress, tumor necrosis factor-alpha, as well as cholinesterase activity. Conversely, ellagic and rosmarinic acid treatment ameliorated such damage, thus showing the possibility to use as an adjuvant during doxorubicin treatment.

In vivo and in vitro evaluation of the effects of domperidone on the gastrointestinal tract of healthy horses.

OBJECTIVE: To determine the effects of domperidone on in vivo and in vitro measures of gastrointestinal tract motility and contractility in healthy horses. SAMPLE: 18 adult horses and tissue samples from an additional 26 adult horses. PROCEDURES: Domperidone or placebo paste was administered to healthy horses in a 2-period crossover study. Gastric emptying was evaluated after oral administration of domperidone paste (1.1 or 5.0 mg/kg) or placebo paste by means of the acetaminophen absorption test in 12 horses. Frequency of defecation, weight of feces produced, fecal moisture, and stomach-to-anus transit time of microspheres were evaluated after administration of domperidone paste (1.1 mg/kg) or placebo paste in 6 horses. The effect of domperidone on smooth muscle contractile activity in samples of duodenum, jejunum, ileum, or colon obtained from 26 horses immediately after euthanasia (for nonsystemic medical problems) was investigated. RESULTS: Oral administration of 5.0 mg of domperidone/kg increased peak plasma acetaminophen concentration and area under the curve, indicating increased gastric emptying. Administration of 1.1 mg of domperidone/kg had no effect on gastric emptying, transit time, defecation frequency, or amount and moisture of excreted feces. Contractile activities of circular and longitudinal muscle strips from the duodenum, jejunum, ileum, or colon were not altered by domperidone. Dopamine increased contractile activity of longitudinal muscle strips but not that of circular muscle strips from the midjejunum. Domperidone decreased the dopamine-induced contractile activity of midjejunal longitudinal muscle strips. CONCLUSIONS AND CLINICAL RELEVANCE: The potential beneficial effects of domperidone in horses with ileus need to be evaluated in horses with decreased gastric emptying or adynamic ileus.

Pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses.

OBJECTIVE: To determine the pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses. ANIMALS: 8 healthy horses. PROCEDURES: A single dose of zoledronic acid (0.057 mg/kg, IV) was administered during a 30-minute period. Venous blood was collected at several time points. Zoledronic acid concentration in plasma was measured by liquid chromatography-tandem mass spectrometry, and pertinent pharmacokinetic parameters were determined. Plasma was analyzed for total calcium, BUN, and creatinine concentrations and a marker for bone resorption (C-terminal telopeptides of type I collagen). RESULTS: Zoledronic acid was safely administered IV during a 30-minute period, and no adverse effects were observed. Plasma concentrations of zoledronic acid were consistent with a 2-compartment mammillary model. Plasma concentrations of zoledronic acid were detected for up to 8 hours after administration. Mean total calcium concentrations in plasma were less than the reference range 7 days after zoledronic acid administration. A marker for bone remodeling decreased in concentration after zoledronic acid administration and remained low for the 1-year duration of the study. No changes in BUN and creatinine concentrations were observed after zoledronic acid administration. CONCLUSIONS AND CLINICAL RELEVANCE: Zoledronic acid was safely administered in healthy horses. Zoledronic acid is reported as the strongest bisphosphonate presently available, and studies evaluating potential benefits of zoledronic acid in horses with orthopedic conditions are warranted.

Use of zoledronate for treatment of a bone fragility disorder in horses.

OBJECTIVE: To assess clinical outcomes and scintigraphic findings in horses with a bone fragility disorder (BFD) treated with zoledronate (a nitrogen-containing bisphosphonate). DESIGN: Prospective uncontrolled clinical trial. ANIMALS: 10 horses with evidence of a BFD. PROCEDURES: Signalment, history, and geographic location of horses' home environments were recorded. Physical examinations, lameness evaluations, and nuclear scintigraphy were performed. Diagnosis of a BFD was made on the basis of results of clinical and scintigraphic examination. Each horse was treated with zoledronate (0.075 mg/kg [0.034 mg/lb, IV, once]) at the time of diagnosis. Horses were reevaluated 6 months after treatment. RESULTS: Affected horses were from the central and coastal regions of California and had ≥ 1 clinical sign of the disorder; these included scapular deformation (n = 2), lordosis (1), nonspecific signs of musculoskeletal pain (1), and lameness that could not be localized to a specific anatomic region (9). All horses had multiple sites of increased radiopharmaceutica uptake during initial scintigraphic evaluation of the axial skeleton and bones of 1 or both forelimbs. Six months after treatment, clinical improvement (defined as improvement in the lameness score, resolution of signs of musculoskeletal pain, or both) was detected in 9 of 10 horses; scintigraphic uptake was unchanged (n = 2) or subjectively decreased (8). No adverse effects attributed to zoledronate treatment were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with zoledronate appeared to be useful in improving clinical outcome and scintigraphic findings in horses with a BFD; however, future placebo-controlled studies are necessary to accurately determine efficacy and long-term safety.

Abdominal computed radiography for the diagnosis of enterolithiasis in horses: 142 cases (2003?2007).

OBJECTIVE: To evaluate the sensitivity and specificity of abdominal computed radiography (CR) for the diagnosis of enterolithiasis in horses and to examine how these parameters are affected by the number and anatomic location of enteroliths and by gas distension of the gastrointestinal tract. DESIGN: Retrospective case series. ANIMALS: Horses ? 1 year old that underwent abdominal CR and subsequent exploratory laparotomy or postmortem examination. PROCEDURES: 3 reviewers blinded to signalment, history, clinical signs, and diagnoses separately evaluated abdominal computed radiographs of horses included in the study. Each set of radiographs was evaluated for the presence or absence of enteroliths, the amount of gas distention, and the image quality. Signalment, definitive diagnosis on the basis of findings on exploratory laparotomy or postmortem examination, and the number and location of enteroliths were obtained from medical records. RESULTS: Of the 142 cases reviewed, 58.4% (83/142) had confirmed enterolithiasis. For the 3 reviewers, overall sensitivity was 85% and specificity was 93%. Sensitivity was lower for small colon enteroliths than for large colon enteroliths (50% and 94.5%, respectively) and was significantly affected by gas distention. Sensitivity was not significantly affected by the number of enteroliths. CONCLUSIONS AND CLINICAL RELEVANCE: Computed radiography provided high sensitivity and high specificity for the diagnosis of enterolithiasis in horses. Caution should be exercised when the radiographic results are negative, as the sensitivity for small colon enterolithiasis was relatively low and gas distension negatively affected detection of enteroliths. Abdominal CR is indicated as a diagnostic test in horses examined for colic in geographic regions in which enterolithiasis is endemic.

Evaluation of the effect of ranitidine on gastroduodenal contractile activity and gastric emptying in horses.

OBJECTIVE: To determine the effect of ranitidine on gastric emptying in horses. ANIMALS: 11 adult horses. PROCEDURES: In vitro, isolated muscle strips from the pyloric antrum and duodenum of 5 horses were suspended in baths and attached to isometric force transducers. Once stable spontaneous contractions were observed, ranitidine or diluent was added at cumulative increasing concentrations. Isometric stress responses were compared. In vivo, 6 horses were assigned to a group in a prospective randomized crossover study design with a wash-out period of 2 weeks between trials. Ranitidine (2.2 mg/kg) or saline (0.9% NaCl) solution was administered IV, and 15 minutes later, acetaminophen (20 mg/kg), diluted in 400 mL of water, was administered via nasogastric tube to evaluate the liquid phase of gastric emptying. Serum acetaminophen concentration was measured at several time points for 3 hours by use of liquid chromatography tandem mass spectrometry. Frequency of defecation was recorded during the 3 hours of the study. RESULTS: Ranitidine increased the contractile activity of the pyloric antrum smooth muscle at a concentration of 10(-4) M. No significant effect of ranitidine on plasma kinetics of acetaminophen was identified. Frequency of defecation did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Ranitidine did increase gastric motility in vitro, but no effect on liquid phase gastric emptying was identified in healthy horses by use of the acetaminophen absorption model. Results do not support the use of ranitidine to promote gastric emptying.

Pull-through technique for palmar digital neurectomy: forty-one horses (1998-2004).

OBJECTIVES: To report outcome of horses treated for navicular syndrome using a pull-through (PT) technique for palmar digital neurectomy (PDN). DESIGN: Retrospective study. ANIMALS: Horses (n=41) with navicular syndrome (NS). METHODS: Medical records (1998-2002) for horses that had NS and failed to respond to conservative management that had unilateral or bilateral forelimb, biaxial PDN were reviewed. Outcome for up to 6 years was obtained by telephone questionnaire or lameness examination. Survival analysis was used to assess time to recurrence of lameness. RESULTS: One year after PDN, 36 horses (88%) were free of lameness. Mean survival with no lameness after surgery was estimated at 4.14+/-0.33 years (median, 5 years). CONCLUSIONS: PT-PDN technique resulted in soundness for 88% of horses for at least 1 year. PT-PDN was easily and quickly performed without specialized equipment, and had a low incidence of complications. CLINICAL RELEVANCE: The PT technique is an effective and viable alternative surgical method for PDN.