Different metabolites induced by deoxynivalenol in the serum and urine of weaned rabbits detected using LC-MS-based metabolomics.

The main toxic effects of deoxynivalenol (DON) are the result of long-term accumulation, and there are no obvious clinical signs at the early stage. Specific metabolites in blood and urine can be used as biomarkers and become an important diagnostic indicator for DON poisoning monitoring. This study aimed to reveal the differences in DON-induced metabolites in the serum and urine of weaned rabbits. Thirty-two weaned rabbits were divided into two groups: control group and DON group. Both groups of rabbits were fed a basic diet. Rabbits in the DON group were administered 1.5 mg/kg b.w. DON by intraperitoneal injection on an empty stomach in the morning every two days. Rabbits in the control group were injected with the same amount of saline every two days in the same way. After the 25-day trial, serum and urine samples from different experimental periods were collected. The results based on the LC-MS/MS method showed that DON can be metabolized rapidly in blood, and urine is the main metabolic pathway for DON. Data based on metabolomics illustrated that underlying biomarkers in serum were mainly involved in glycerophospholipid metabolism, tryptophan metabolism and pentose and glucuronate interconversions, while those in urine samples were involved in caffeine metabolism, glycine, serine and threonine metabolism, and terpenoid backbone biosynthesis. Correlation analysis suggested that DON can induce changes in certain disease-related metabolites in serum and urine. In conclusion, the pathogenic mechanism of DON includes multiple levels, indicating that DON poisoning is caused by multiple factors acting on multiple links.

Effect of cation-anion balance in feed on urine pH in rabbits in comparison with other species.

In the present investigation, the impact of diet composition on urine pH in rabbits was compared with previous studies on rabbits, cats, dogs, pigs and horses. A total of 13 dwarf rabbits were fed six different diets with a cation-anion balance (CAB) between -39 and +320 mmol/kg dry matter (DM) using ammonium chloride (NH4 Cl) as an acidifier. CAB was calculated as follows: CAB (mmol/kg DM) = 49.9*Ca + 82.3*Mg +43.5*Na + 25.6*K - 59*P - 62.4*S - 28.2*Cl; minerals in g/kg DM. Urine, faeces and blood were collected. Urine pH ranged from 5.26 ± 0.22 at a CAB of -39 mmol/kg DM to 8.56 ± 0.24 at a CAB of +320 mmol/kg DM. A low CAB in the feed reduced blood pH and blood base excess significantly. Renal excretion of Ca, P, Na and Mg and water was significantly higher in rabbits eating acidifying diets. In comparison with other species, rabbits reacted to acidifying diets in a similar way as cats, dogs and pigs. Rabbits on a mildly alkalizing diet, however, had a trend to higher urine pH than other monogastric species on such diets (cats, dogs, pigs, horses).

γ-Glutamyl-transferase (GGT) activity in the urine of clinically healthy domestic rabbits (Oryctolagus cuniculus).

Free-catch urine samples were collected from forty-one clinically normal domestic rabbits of various ages, breeds and both sexes. The Test γ GT Liquid-0018257640 was used for the in vitro quantitative determination of γ-Glutamyl-transferase (GGT) and reference intervals for γ-glutamyl transferase (γ-glutamyl transpeptidase, γ-GT, GGT) and GGT index (γ-glutamyl transferase to creatinine ratio) were established in fresh urine samples. Possible correlations of GGT and GGT index with sex and age were also explored. The stability of GGT after storage at +4°C for one week and -20°C for one month was investigated. The GGT and the GGT index reference intervals in fresh urine samples of healthy domestic rabbits were found to be 2.7-96.5 IU/l and 0.043-1.034, respectively. The urine GGT activity and the GGT index did not differ significantly between sexes in fresh urine samples. Nevertheless, a statistically significant difference was found in the GGT index with neutered status. Short-term storage at 4°C did not alter the enzyme stability, whereas, freezing did. Further investigations are needed to determine whether these parameters may be useful for early detection of renal tubular damage in rabbits, and in enabling better clinical management of affected animals.

Mechanisms for eliminating monoterpenes of sagebrush by specialist and generalist rabbits.

Pygmy rabbits (Brachylagus idahoensis) are one of only three vertebrates that subsist virtually exclusively on sagebrush (Artemisia spp.), which contains high levels of monoterpenes that can be toxic. We examined the mechanisms used by specialist pygmy rabbits to eliminate 1,8-cineole, a monoterpene of sagebrush, and compared them with those of cottontail rabbits (Sylvilagus nuttalli), a generalist herbivore. Rabbits were offered food pellets with increasing concentrations of cineole, and we measured voluntary intake and excretion of cineole metabolites in feces and urine. We expected pygmy rabbits to consume more, but excrete cineole more rapidly by using less-energetically expensive methods of detoxification than cottontails. Pygmy rabbits consumed 3-5 times more cineole than cottontails relative to their metabolic body mass, and excreted up to 2 times more cineole metabolites in their urine than did cottontails. Urinary metabolites excreted by pygmy rabbits were 20 % more highly-oxidized and 6 times less-conjugated than those of cottontails. Twenty percent of all cineole metabolites recovered from pygmy rabbits were in feces, whereas cottontails did not excrete fecal metabolites. When compared to other mammals that consume cineole, pygmy rabbits voluntarily consumed more, and excreted more cineole metabolites in feces, but they excreted less oxidized and more conjugated cineole metabolites in urine. Pygmy rabbits seem to have a greater capacity to minimize systemic exposure to cineole than do cottontails, and other cineole-consumers, by minimizing absorption and maximizing detoxification of ingested cineole. However, mechanisms that lower systemic exposure to cineole may come with a higher energetic cost in pygmy rabbits than in other mammalian herbivores.

Influence of diet on calcium metabolism, tissue calcification and urinary sludge in rabbits (Oryctolagus cuniculus).

Rabbits absorb more calcium (Ca) from their diet than they require, and excrete surplus via urine, which therefore contains a typical 'sludge'. This makes rabbits susceptible to Ca-containing uroliths. But given the Ca content of diets of free-ranging specimens, and the limited reports of urinary sludge and Ca contents in free-ranging lagomorphs, we can suspect that rabbits are naturally adapted to high urinary Ca loads. We fed four groups of New Zealand hybrid rabbits [n = 28, age at start 5-6 weeks) pelleted diets consisting of lucerne hay only (L, Ca 2.32% dry matter (DM)], lucerne:oats 1:1 (LG, Ca 1.36%), grass hay only (G, Ca 1.04%), or grass:oats 1:1 (GG, 0.83%) for 25 weeks, with water available ad libitum. Diets were not supplemented with Ca, phosphorus, or vitamin D. Rabbits on diets LG and GG had lower food and water intakes, lower faeces and urine output, grew faster and had higher body mass at slaughter (mainly attributable to adipose tissue). Apparent Ca digestibility decreased in the order L-LG-G/GG. Rabbits on L had larger and heavier kidneys, more urinary sediment at sonography, and a higher urinary Ca content than the other groups. No animal showed signs of urolithiasis/calcinosis at X-ray, sonography, or gross pathology. Kidney/aorta histology only sporadically indicated Ca deposits, with no systematic difference between groups. Under the conditions of the experiment, dietary Ca loads in legume hay do not appear problematic for rabbits, and other factors, such as water supply and level of activity may be important contributors to urolithiasis development in veterinary patients. However, due to the lower Ca content of grass hay, the significantly lower degree of urinary sludge formation, and the significantly higher water intake related with grass hay feeding, grass hay-dominated diets are to be recommended for rabbits in which urolithiasis prevention is an issue.

Urinary protein:creatinine ratio in rabbits in relation to their serological status to Encephalitozoon cuniculi.

The concentrations of protein and creatinine were measured in urine samples from 74 healthy domestic pet rabbits, 54 of them seronegative to Encephalitozoon cuniculi and 20 seropositive. The calculated reference range for the urinary protein:creatinine ratio (UPC) of E cuniculi-seronegative rabbits was 0.11 to 0.40. There was no significant variation in the UPC due to the bodyweight, breed, sex, neutered status or husbandry of the rabbits. Seroconversion to E cuniculi was not found to be associated with clinical renal disease because none of the seropositive rabbits had azotaemia or proteinuria.

Clinical pathology of the domestic rabbit. Acquisition and interpretation of samples.

Diagnostic laboratories are receiving increasing numbers of samples from practitioners as they strive to diagnose complex disease processes and manage rabbit cases. Proper acquisition of diagnostic samples and interpretation of results are key skills necessary for successful management of medical cases. This article reviews the collection and interpretation of clinicopathologic samples commonly used in rabbits.

Nephrotoxicity of tiletamine in New Zealand white rabbits.

Tiletamine and zolazepam, the two constituents of Telazol, were evaluated independently to determine which agent was responsible for the nephrotoxicity caused by Telazol in New Zealand White rabbits. Five rabbits were injected i.m. with 32 mg/kg of tiletamine, four animals received 7.5 mg/kg of tiletamine, and five rabbits received 32 mg/kg of zolazepam. Urinalysis was performed and blood urea nitrogen and serum creatinine were monitored for 7 days postinjection. In all five rabbits injected with the high dose of tiletamine, blood urea nitrogen and creatinine rose by 3 days postinjection and increased steadily throughout the week. By 4 days postinjection, urine protein and glucose were elevated and cellular and protein casts were present. No serum chemistry or urine abnormalities were detected in rabbits receiving low doses of tiletamine, zolazepam, or in the four control rabbits. All animals were euthanized and necropsied at 7 days postinjection. Histopathology showed severe renal tubular necrosis in all five rabbits injected with 32 mg/kg tiletamine. Mild nephrosis was present in three of four rabbits injected with 7.5 mg/kg of tiletamine. No lesions were present in the zolazepam-injected or control rabbits. The results of this study show that tiletamine is the constituent responsible for the nephrotoxicity of Telazol in rabbits. They further demonstrate that doses commonly used for anesthetic induction or restraint can produce renal lesions in rabbits.