Iraqi Journal of Veterinary Sciences

Despite the widespread use of xylazine in veterinary medicine, studies on its neurotoxicity are limited. So, our current study aims to reveal its neurotoxicity in chicks by determining the (LD₅₀) of xylazine in Dixon's procedure. Moreover, it aims to study the effects of a small and repeated dose of xylazine on neurobehavioral test and the toxic doses of xylazine on the concentration of (glycine and glutamate) in the plasma of chicks and on the brain tissue after 60 and 90 minutes of injection. The LD₅₀ of xylazine by injection into the chest muscle was 26.65 mg/kg. The injection of xylazine at a dose of 3 and 6 mg/kg in the chest muscle for three consecutive days caused an inhibition in motor activity within the open field as well as a significant elevation in the tonic immobility test response, injection of xylazine at doses 48.96 mg/kg ,60 and 90 minutes after the injection led to a significant increase in the glycine concentration as well as a significant decrease in glutamate after 90 minutes in the plasma of chicks, accompanied by histological variation in the brain tissue characterized by necrosis of neurons, vasogenic edema, neurophagia, cavities, infarction, necrosis of Purkinjean cell with decrees in the number of it. Our results revealed that xylazine had neurotoxic effects in chicks, represented by inhibition of neural behavior and motor activity within the open field, accompanied by a change in the concentration of glycine and glutamate in the plasma of chicks and histological variation in the brain tissue of chicks.

The objective of this projectwas to study the induction of smooth anesthesia characterized by good induction (hypnosis), analgesia and good recovery with mild side effects caused by drugs. The effect of using Ketamine with both xylazine and midazolam KXM was investigated in adult rabbitsand compared with the positive control group that was administered with ketamine alone K at 40 mg/kg i.m, and with ketamine - xylazine group KX at 40 and 4 mg/kg i.m respectively, and with ketamine - midazolam group KM also at 40 and 4 mg/kg i.m respectively. Administration of xylazine and midazolam each one alone at 4 and 2 mg/kg I.M induced analgesia in a dose-dependent manner through a significant elevation of the electrical voltage after injection when compared with its value before injection. A minimum doses of a mixture KXM at 20,2 and 2 mg/kg i.m respectively, induced good hypnosis with rapid induction and long duration with recovery periods without significant variations in vital physiological parameters (respiratory rate, heart rate, and rectal temperature) and some biochemical parameters (GPT and GOT and glucose level) comparing with groups K, KX and KM. The outcomes of this work were revealed to the induction of proficient general anesthesia that was described by effective hypnosis with analgesic efficacy throughout the administration a minimum doses of ketamine/xylazine/midazolam combination in rabbits.

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by food and drug administration (FDA) as harmless adjuvant and is largely used in drug systems delivery. Physicochemical and biological possessions of TPGS provide many advantages for its usage in drug delivery, such as high bio-compatibility, increased drug solubility, improved drug penetration and selective anti-tumor action. The aim of the study was to use the TPGS polymer as a drug release model to regulate the release of the anesthetic xylazine-ketamine in order to minimize therapeutically reference dose, avoid side effects, and improve efficacy. The study performed on 15 adult local breed male rabbits, divided into 3 groups with same number which injected intramuscularly with single dose of suggested anesthetics. Group 1 injected with ketamine and xylazine. Group 2 injected with ketamine and xylazine as same dose of group 1 loaded by PLGA-TPGS. Group 3 injected with Ketamine and xylazine loaded by PLGA-TPGS with half dose of Group 1 and 2. The following physiological parameters were evaluated: heart rate, respiratory rate, degree of muscle relaxation, onset of action and stages of anesthesia before administration the drug at time zero then at 10, 30 and 60 minutes after drug administration, also induction of anesthesia, surgical anesthesia and recovery time were recorded. Nanoprecipitation technique was optimal method for preparing small particle size as well as reduce dose for therapeutic effect. Small and large dose was showed perfect analgesic and muscle relaxant activity of xylazine-ketamine drugs. Ketamine 30 mg and xylazine 10 mg loaded PLGA showed elevation of conciseness period as well as increase muscle relaxant. Ketamine 30 mg and xylazine 10 mg loaded PLGA reduce heart rate but onset of action delayed when compared with reference drug. The process of nanoprecipitation was ideal for forming small particle sizes and reducing the dosage for therapeutic effects. PLGA loaded with ketamine-xylazine demonstrated improved cycle concentration (walk time) as well as improved muscle relaxant, finally the protocol created an excellent anesthetic combination for induction of general anesthesia. 

The study was designed to qualitative and quantitative evaluation of the antinociceptive effect of metoclopramide and xylazine each alone or as a concomitant administration in mice. Adult albino Swiss mice weighing 20-30 mg used in all experiments. By using the hot plate test, the individual analgesic dose (ED₅₀) of metoclopramide and xylazine detected depending on the up and down method. Isobolographic analysis used to evaluate the type of interaction between two drugs at the ratio 0.5:0.5 of individual ED₅₀ for each drug at the level of antinociception effect. Simultaneously administration of the double dose of individual ED₅₀ and low doses (sedative, non-analgesic doses) of both drugs, also evaluated at the level of central and visceral analgesia using a hot plate and writhing response test respectively. The individual ED₅₀ of xylazine and metoclopramide was 10.8 and 25.6mg/kg IP respectively. A synergistic interaction at the level of analgesia explored between two drugs at ratio 0.5:0.5 which represented as decreased in ED₅₀ of metoclopramide and xylazine by 58.75 and 58.15% respectively. The animal suffered from only slight sedation and docile. Simultaneously IP administration of xylazine and metoclopramide at double dose of ED₅₀ for each drug-induced significant increase in latency time of thermal response, as well as a significant decrease in writhes number, which induced by acetic acid in comparison with control groups. The percentage of analgesia at sub analgesic doses of a concomitant administration of both drugs was 100% in comparison with each drug alone. These results suggested safe and good use of both drugs in veterinary medicine.