Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats.

Aditoprim (ADP) is a newly developed antibacterial agent in veterinary medicine. The metabolism and disposition of ADP in swine, broilers, carp and rats were investigated by using a radio tracer method combined with a radioactivity detector and a liquid chromatography/ion trap/time-of-flight mass spectrometry. After a single oral administration, more than 94% of the dose was recovered within 14 d in the four species. The urine excretion was dominant in swine and rats, making up 78% of the dose. N-monodesmethyl-ADP, N-didesmethyl-ADP, and 10 new metabolites were characterized. These metabolites were biotransformed from the process of demethylation, α-hydroxylation, N-oxidation, and NH2-glucuronidation. After an oral dose for 7 d, ADP-derived radioactivity was widely distributed in tissues, and high concentrations were especially observed in bile, liver, kidney, lung, and spleen. The radioactivity in the liver was eliminated much more slowly than in other tissues, with a half-life of 4.26, 3.38, 6.69, and 5.21 d in swine, broilers, carp, and rats, respectively. ADP, N-monodesmethyl-ADP, and N-didesmethyl-ADP were the major metabolites in edible tissues. Notably, ADP was detected with the highest concentration and the longest duration in these tissues. These findings indicated that ADP is the marker residue and the liver is the residue target tissue.

Przewalski's naked carp (Gymnocypris przewalskii): an endangered species taking a metabolic holiday in Lake Qinghai, China.

The naked carp is an endangered cyprinid that migrates annually between freshwater rivers, where it spawns, and Lake Qinghai, where it feeds and grows. Lake Qinghai is a high-altitude lake (3,200 m) in western China that currently exhibits the following composition (in mmol L(-1): [Na(+)] 200, [Cl(-)] 173, [Mg(2+)] 36, [Ca(2+)] 0.23, [K(+)] 5.3, total CO(2) 21, titration alkalinity 29; osmolality 375 mOsm kg(-1); pH 9.3), but concentrations are increasing because of water diversion and climate change. We studied the physiology of river water to lake water transfer. When river fish are transferred to lake water, there is a transitory metabolic acidosis followed by a slight respiratory alkalosis, and hemoconcentration occurs. All plasma electrolytes rise over the initial 48 h, and final levels in lake water-acclimated fish are very close to lake water concentrations for [Na(+)], [Cl(-)], [K(+)], and osmolality, whereas [Ca(2+)] continues to be regulated well above ambient levels. However, [Mg(2+)] rises to a much greater extent (fourfold in 48 h); final plasma levels in lake fish may reach 12 mmol L(-1) but are still much lower than in lake water (36 mmol L(-1)). At the same time, urine flow rate decreases drastically to <5% of river water values; only the renal excretion of Mg(2+) is maintained. Both gill and kidney Na(+),K(+)-ATPase rapidly decline, with final levels in lake water fish only 30% and 70%, respectively, of those in river water fish. Metabolic rate also quickly decreases on exposure to lake water, with O(2) consumption and ammonia-N excretion rates eventually falling to only 60% and 30%, respectively, of those in river fish, while plasma ammonia rises fivefold. The fish appear to be benefiting from a metabolic holiday at present because of decreases in iono- and osmoregulatory costs while in lake water; elevated plasma [Mg(2+)] and ammonia may be additional factors depressing metabolic rate. If the lake continues to dehydrate, these benefits may change to pathology.

Effects of a parasite-induced nephritis on osmoregulation in the common carp Cyprinus carpio.

Carp Cyprinus carpio infected with the haemoflagellate Trypanoplasma borreli undergo progressive nephritis associated with a destruction of approx. 40% of the nephric tubules. In an attempt to analyse the effect of the nephritis on the osmoregulation of affected carp, the clinical chemical properties of plasma and urine samples were analysed. Parasitised carp excreted greater amounts of electrolytes in their urine than uninfected carp which excreted highly diluted urine with an osmolality of about 10% of plasma osmolality. During the course of the infection, urine osmolality increased up to 26% of plasma osmolality by Day 21 post-infection (p.i.). The plasma:urine ratio of Na+ also increased, while concomitant losses of Mg2+, Ca2+, K+ and inorganic phosphate were less pronounced. Infected carp were able to maintain a normal solute balance in their plasma. Plasma hydration (indicated by decreased protein contents) occurred on Day 21 p.i. Our data indicate that in T. borreli-infected carp, reabsorption processes of the distal renal tubule were disturbed, while secretory and absorption processes in the proximal tubule appeared to be less affected. In addition, infected carp were able to compensate their increased ion losses, probably by (energy-consuming) active absorption processes. The energy budget of infected carp was additionally affected by a substantial direct consumption of plasma glucose by the parasite.

Effects of hypoxia on renal function in carp, Cyprinus carpio.

1. Changes in urine and blood properties and heart rate (HR) of carp were investigated during and following hypoxia. 2. When carp were exposed to hypoxic conditions, urine flow in some carp increased immediately. However, it decreased gradually with time. Osmotic pressure and Na+, Cl-, Ca2+ and Mg2+ levels in urine increased in contrast to urine flow. K+, P, ammonium, and lactic acid levels in urine increased gradually. 3. When carp lost their balance, blood pH and plasma K+ were lower, and RBC, Ht, Hb, Mg2+, P, ammonium, lactic acid, and glucose in plasma were higher than those of the control. 4. As water-dissolved oxygen level was restored, urine flow increased immediately and soon decreased to the control rate. Other urine properties showed higher values than the initial levels and decreased with time. No significant change was found in urinary protein. 5. The relationship between HR and urine flow is discussed.

Influence of nutritional status on the daily patterns of nitrogen excretion in the carp (Cyprinus carpio L.) and the rainbow trout (Salmo gairdneri R.).

Nitrogen (ammonia and/or urea) excretion in carp and rainbow trout kept under different feeding regimes was continuously monitored over 24-hr cycles. The daily nitrogen excretion patterns resulting from these feeding regimes were studied over several days after a change from one made to another. Constant levels of endogenous nitrogen excretion were reached about one week after the start of a fasting period; almost one week was needed for the daily nitrogen excretion pattern to stabilize after the feeding rhythm was changed. Overall daily nitrogen excretion rates were directly related to nitrogen consumption in carp as well as in trout. The rate of ammonia excretion increased immediately after each meal; the maximum rate occurred at different intervals, depending on the amount of nitrogen intake as well as on the time-lapse after a particular feeding regime was initiated. Contrary to data on sockeye salmon, post-digestive nitrogen excretion rate was distinctly different from the ENE rates observed during fasting in carp and rainbow trout.