Nephrotoxicity of cyclosporin A in diabetic breeding rats breeding rats

A considerable number of studies were carried out on patients receiving Cyclosporin A (CSA) after bone marrow, heart and kidney transplants. More recently this drug has been used as an immunosuppressive agent in the management of type 1 diabetes. Moreover the increase of creatinine levels in CSA-treated patients and animals has led the researchers to believe that this drug may be responsible for irreversible nephrotubular side effects.Our aim was, therefore, to study the hispathological effects of CSA on kidneys of bio breeding (BB) rats, which develop diabetes spontaneously.Animals were treated for 30 and 60 days with daily injections of 8 mg/kg body wt of CSA, dissolved in 2 ml of Intralipid 10% (Pierrel), given intraperitoneally (control animals received only Intralipid). At the end of the experiments animals were sacrificed under ether anaesthesia and the kidneys removed and processed for light microscopy, using standard procedures. After a 30-day administration of CSA, the tubular and glomerular structures appeared unchanged or, in some cases, only a few cells, in the proximal tubules, showed slight vacuolation. After 60 days of CSA administration, the elements of the proximal profiles showed a considerable degree of cytoplasmic vacuolation. These vacuoles resulted positive to PFABB, Sudan Black B, PAS and alkaline tetrazolium reactions. Distal tubular profiles, loops of Henle and glomeruli were unaffected.Our morphological findings demonstrate that CSA causes nephrotubular modifications, when administered in therapeutic doses of only 10 mg/kg body wt, as in many clinical schedules. Moreover data could be consistent with a possible reversion to the normal structural appearance.     

Non-opioid-induced tolerance in rats

It is shown that systemic injections of analgin and ketorolac in doses equivalent to those used in clinics induce antinociception in awake rats (tail-flick test) and, when carried out repetitively, induce tolerance to these agents and cross-tolerance to morphine (blocked by naloxone). Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 370–373, July–August, 2006.     

Thermoregulation in hypergravity-acclimated rats

To determine the effect of hypergravity acclimation on thermoregulation, core temperature (Tc), tail temperature (Tt), and O2 consumption (VO2) were measured in control rats (raised at 1 G) and in rats acclimated to 2.1 G. When the animals were exposed to a low ambient temperature of 9 degrees C, concurrently with a hypergravic field of 2.1 G, Tc of rats raised at 1 G fell markedly by approximately 6 degrees C (to 30.8 +/- 0.6 degrees C) while that of the rats raised at 2.1 G remained relatively constant (falling only approximately 1 degree C to 36.4 +/- 0.3 degrees C). Thus prior acclimation to a 2.1-G field enabled rats to maintain Tc when cold exposed in a 2.1-G field. To maintain Tc, thermogenic mechanisms were successfully activated in the 2.1-G-acclimated rats as shown by measurements of VO2. In contrast, VO2 measurements showed that rats reared at 1 G and then cold exposed at 2.1 G did not activate thermogenic mechanisms sufficiently to prevent a fall in Tc. In other experiments, rats acclimated to either 1 or 2.1 G were found to lack the ability to maintain their Tc when exposed to a 5.8-G field or when exposed to prolonged cold exposure at 1 G. Results are interpreted as showing that when placed in a 2.1-G field, rats acclimated to 2.1 G can more closely maintain their Tc near 37 degrees C when cold exposed than can rats acclimated to 1 G. However, this enhanced regulatory ability of 2.1-G-acclimated rats over 1.0-G-acclimated rats is restricted to 2.1-G fields and is not observed in 1.0- and 5.8-G fields.     

Gustatory contrast in rats

Six groups of rats were presented with alternating 45-sec accessperiods to two tubes containing sucrose solutions. On some daysone group experienced a disparity in solution concentration(16% vs. 2%, 16% vs. 4%, 16% vs. 8%, and 16% vs. 12%) and onother days received the same concentration solution in bothtubes (16%, 12%, 8%, 4%, or 2%). Each of the remaining fivegroups received only one concentration solution in both tubesthroughout the experiment (16%, 12%, 8%, 4%, or 2%). Lick ratesto the different concentration solutions obtained under comparisonconditions were found to be exaggerated relative to those obtainedunder non-comparison conditions (contrast). Regression analysesperformed on the log lick ratios to the various concentrationsplotted as a function of the log ratios of the concentrationsavailable, revealed a good fit to a power function with an exponent(slope) within the range of those found in human judgments ofrelative sweetness. The slopes obtained from the regressionanalyses were a) steeper under comparison than under non-comparisoncondition and b) increased as number of within-session comparisonsincreased. The results are discussed in terms of a sensoryperceptualinterpretation of contrast effects.     

Nicotine dependence in rats

Health hazards associated with nicotine and tobacco use are well known. A contributing factor, the dependence producing potential of this drug, has become widely accepted. However, there are only a few human and animal studies that provide objective measures of the behavioral consequences of nicotine abstinence. The purpose of the present experiment was to use sensitive measures to examine behavioral disruptions that resulted when nicotine administration was terminated. Six rats were administered 96 daily intravenous infusions of nicotine (0.125 mg/kg/infusion) for at least 10 days. They were trained to respond on a tongue-operated solenoid-driven drinking device that delivered 0.005 ml of a glucose and saccharin solution (G + S) per lick. When nicotine access was terminated for six days, there was a marked suppression in behavior reinforced by the sweetened solution, and this disruption was immediately reversed when nicotine was reinstated. In contrast, nicotine removal also resulted in a decrease in food intake on the first day, but on subsequent days food intake was significantly higher than when nicotine was administered. When cotinine (0.25 mg/kg/infusion), a metabolite of nicotine was substituted for nicotine for six days, similar disruptions resulted in responding maintained by G + S, but food intake was not significantly decreased on the first day of nicotine abstinence. These findings illustrate the utility of sensitive behavioral tests to reveal effects of nicotine abstinence.     

Kemantane pharmacokinetics in rats

Pharmacokinetics of novel immunostimulating drug kamantane was studied by using gas-liquid chromatography in experiments on rats. It was found that kemantane biotransformed rapidly after oral administration with the forming of active metabolite. Kemantane and its metabolites are distributed rapidly from the blood to organs. The drug is eliminated from the organism of rats as metabolite.     

Anaerobic threshold in rats

• 1.1. The aim of this study was to find out whether the anaerobic threshold (AT) can be estimated in rats running at increasing speed and if so what is the reproducibility of the measurements.
• 2.2. Lactate (LA) concentrations in blood taken from 11 rats were determined during a discontinued, multistage treadmill exercise test repeated four times in each animal.
• 3.3. It was found that blood LA changes vs speed have an exponential pattern with a distinct, rapid rise at the speed above 25 m/min which corresponds to blood LA of approx. 4 mmol/1.
• 4.4. The variation coefficient of the speed at which AT occurred in individual animals ranged between 10 and 20%.
• 5.5. These results offer a potential application of AT determination in the animal studies concerning mechanisms controlling exercise metabolism.