Healthy Rabbits Research Articles

Effects of intranasal and intramuscular administration of butorphanol and zolazepam-tiletamine combination on intraocular pressure and tear secretion in New Zealand White rabbits.

This study aimed to compare the effect of intranasal (IN) and intramuscular (IM) administration of butorphanol and zolazepam-tiletamine (ZT) combination on intraocular pressure (IOP) and tear secretion (TS) in rabbits. Fourteen healthy male New Zealand White rabbits weighing 3.05 ± 0.72 kg, aged between 1 and 2 years old, were included in the study. Animals randomly received 0.5 mg/kg butorphanol and 15 mg/kg ZT combination either with IN or IM administration. IOP and TS were measured at baseline (T0), and followed by 5, 15, 30, 45, and 60 min after drug administration. The sedation variables, the time to onset of sedation, duration of sedation, and sedation scores were also recorded. The route of administration for the butorphanol and ZT combination had no significant effect on the mean IOP (p = .301) and TS (p = .445). Furthermore, there were no significant changes observed in the IOP (p = .472) and TS (p = .348) over time. The time to onset of sedation was earlier in the IN group (4.57 ± 0.79 min) than in the IM group (5.86 ± 0.9 min; p = .0004). The duration of sedation was significantly longer for IM (57.43 ± 3.41 min) compared with IN (45.0 ± 1.91 min; p < .0001). No significant difference in the sedation score was observed between groups at all time points. In conclusion, both IN and IM administration of the butorphanol and ZT combination in rabbits had similar effects on IOP and TS.

Radiological and laboratory prognostic parameters for gastric dilation in rabbits (Oryctolagus cuniculus).

The aim of this study was to evaluate the radiographical and laboratory findings in pet rabbits with gastric dilation (GD) and identify prognostic parameters. One hundred and fifty-five rabbits with GD were included for the radiographical analyses and 75 for the laboratory analyses. A vertebral stomach score (VSS) was established to determine the extension of the stomach on lateral radiographs. In addition, the caudal limit of gastric distention and the extension and position of gas accumulation in the stomach were recorded. The VSS was significantly higher in rabbits with GD than in healthy rabbits (p=0.001). Extensive amounts of gas accumulation in the stomach (p=0.001) and a ventral or central location of gas accumulation (p=0.023) were associated with significantly increased mortality. Azotemia (51%), hyperglycaemia (44%) and hyponatraemia (37%) were the most frequent biochemical alterations in rabbits with GD. Dueto the retrospective nature of the data, the cause of GD could not be determined in all animals. Rabbits with GD and severe alterations in glucose, creatinine and sodium concentrations, ventral or central gas accumulations and a large amount of gas in the stomach had a poor prognosis.

Exploring the Advance Data Mining Tool for Optimization of Nanoparticles Laden in situ Gel for Ocular Drug Delivery

Background: Glaucoma is widely treated using eye drops, but around 95% of the drug is lost by the ocular barrier resulting in low bioavailability. The incorporation of polymeric nanoparticles into mucoadhesive polymer containing in situ gel is generally helpful in the retention of nanoparticles on the eye and improves the efficacy of the formulation Objective: The objective of the present investigation has to develop polymeric brinzolamide (BRZ) nanoparticles laden with timolol maleate (TM) in situ gel formulation. Methods: The optimized BRZ nanoparticles were prepared using PLGA by nanoprecipitation technique utilizing 32 full factorial designs (FFD). Healthy New Zealand White Rabbit (250-300 g) was used for the pharmacokinetic and pharmacodynamic study. Design of the experiment was applied to optimize formulation and validate the model. Some evaluation parameters related to BRZ nanoparticles as well as in-situ gel, have been done Results: The results of FFD reveal that the optimized condition for drugs to polymer ratio (1:7) containing 0.98 %w/v for poloxamer 188 results in higher entrapment efficiency and drug release with 156.7 nm particle size. The in-situ gel formulation has been prepared using Gelrite (0.5%w/v), and HPMC K4M (0.5%w/v) shows acceptable results with sustained drug release up to 6±0.1 h. The rabbit model's in-vivo pharmacokinetics and pharmacodynamic data showed sustained release of drugs longer than the marketed formulation. Conclusion: The proposed formulation could successfully deliver therapeutic concentrations in the eye with prolonged resident time and serve as a potential alternative for the treatment of glaucoma.

Administration of meloxicam before rather than after castration on eating, defecation and pain indicators in pet rabbits (Oryctolagus cuniculus)

AbstractBackgroundRabbits are extremely sensitive to pain. There is evidence on whether non‐steroidal anti‐inflammatory medication should be administered before or after surgery in rabbits.ObjectivesIn this study, we compared the pain scores and behaviours of rabbits administered meloxicam before or after routine castration.MethodsForty‐two healthy rabbits undergoing castration were randomly assigned to receive meloxicam (1 mg/kg SC) 1 h before or upon recovery from anaesthesia. Several parameters were recorded, including the occurrence of eating, defecating and pain scores postoperatively and change in heart rate intraoperatively.ResultsAt 4 h after surgery, eating was observed in 43% (9/21) of rabbits that received meloxicam before neutering and in 29% (6/21) of rabbits that received meloxicam after. The morning after the surgery, eating was observed in 62% (13/21) of rabbits that received meloxicam before neutering and in 57% (12/21) of rabbits that received meloxicam after. The odds of not eating increased by 1.16 times (1.03–1.29; p = 0.01) per month of age, whereas there was no significant association between eating and administration of meloxicam before or after surgery, body weight and time. Similarly, defecation, pain score and change in heart rate did not differ in animals receiving meloxicam before or after surgery.ConclusionsAdministration of meloxicam in rabbits undergoing castration before or after surgery does not have a relevant effect on eating, defecating or pain score. Younger rabbits show less obvious signs of pain and are more likely to resume eating habits sooner after surgery compared to older rabbits.

Comparative evaluation of mechanical injury methods for establishing stable tracheal stenosis animal models

The study aimed to assess the stability of various mechanical injury techniques in creating tracheal stenosis animal models using endoscopic assistance and investigate the viability of tracheal stoma in this process. Twenty-six healthy adult New Zealand white rabbits were randomly assigned to an experimental and control group. The experimental group underwent tracheal incision followed by steel brush scraping with endoscopic assistance, while the control group received nylon brush scraping. Within the control group, two subgroups were formed: Group A underwent scraping without tracheal stoma, and Group B underwent scraping followed by tracheal stoma. Additionally, a sham operation was performed on a separate group without subsequent scratching, resulting in no stenosis formation. Endoscopic observations were conducted at 7, 14, and 21 days post-scraping, followed by histological examinations of euthanized rabbits on the 21st day. Notably, all rabbits in the non-stoma group survived without complications, whereas Group B rabbits faced mortality post-operation. Histological assessments revealed inflammatory cell infiltration, fibroblast proliferation, and collagen fiber deposition in narrowed tracheal specimens. Steel brush scraping with endoscopic assistance proved more effective in inducing stable tracheal stenosis compared to nylon brush scraping. However, the survival challenges of rabbits with tracheal fistula require further investigation.

Histological Assessment of the Effect Laser Irradiation on Full-Thickness Skin Wound Healing in Rabbits Models

Since there is currently no ideal treatment, wound healing impairment is a significant clinical challenge that is the subject of ongoing research into effective wound healing strategies. As a result, it has been demonstrated that low level laser therapy (LLLT), which is used for wound healing, can effectively control both the local and the systemic response. This study was conducted on 24 adult, clinically healthy male rabbits for this purpose. On each animal's back, full-thickness excisional wounds measuring 2 cm x 2 cm were created following sterile skin preparation. The animals were randomly split into two equal groups, each with twelve rabbits. In the group that acts as a control; 5 milliliters of phosphate-buffered saline was used to treat wounds. In the group treated; for the first seven days, the wounds were only treated with (LLLT) at a rate of 5/5 second at 8j/cm2. At the seventh, fourteenth, and 35th days of healing, histopathological biopsies were performed. The control group's histopathology revealed hemorrhage with inflammatory cell infiltration, primarily neutrophils, and congested blood vessels in the gap seven days after surgery. Necrotized neutrophils, hemolysis, and granulation tissue under the dermis were present in the gap at fourteen days. Between the muscle fibers, there was hemolysis. At 35 days, there was irregular proliferation of fibrous connective tissue, and congested blood vessels with mononuclear cell infiltration could be seen in the gap. At seven days, the treated group has completely sloughed the epidermis and a thin crust on the skin's surface with a small incision. In the dermis, there is a lot of infiltration of inflammatory cells, mostly lymphocytes and macrophages. There is also a lot of granulation tissue and a lot of adipose tissue with a lot of thick collagen network. At fourteen days, the epidermis' epithelial layers have healed completely and a keratinized layer is present. In the dermis, a proliferating and thick collagen network, scattered inflammatory cells, and regular fibrosis with hemorrhage and the development of a new B.V. At day 35, look for narrow scar tissue with complete epithelization, a keratinized layer above the epidermis, new vascularization with a lot of regular fibrosis and few regular collagen, new hair follicles, new blood vessels, and scattered macrophages. We concluded that full-thickness wound healing is positively influenced by the use of low level laser therapy (LLLT), which creates a microenvironment favorable to cell growth and differentiation.

DEVELOPMENT AND IN VIVO EVALUATION OF ABACAVIR SULPHATE MUCOADHESIVE BUCCAL FILMS

Objective: The objective of the study was to evaluate the pharmacokinetic parameters of abacavir sulphate mucoadhesive buccal films in vivo. Methods: Abacavir sulphate mucoadhesive buccal films were developed using the solvent casting method and the prepared buccal films were evaluated for qualitative and quantitative parameters. Pharmacokinetic parameters (maximum plasma concentration [Cmax], maximum plasma concentration [Tmax], area under the curve [AUC], and biological half-life [t1/2]) were evaluated in vivo using healthy albino white rabbits. The blood samples were collected evaluated and the results were compared with Ziagen a reference standard. The Modern Version 6 software and the pharmacokinetic function (Microsoft Excel add-in) applications were used to conduct the statistical study. Results: The abacavir sulphate mucoadhesive buccal films were prepared successfully and the evaluated qualitative and quantitative parameters were within in the acceptable range. The results of the study stated that Cmax, Tmax, AUC0-t, AUC0-α, and t1/2 of abacavir sulphate mucoadhesive buccal film were found to be 93.86 ng/ml, 8 h, 1652.21 ng/ml×h, 2939.76 ng/ml×h, and 17.96 h, respectively. These results were comparable with the reference standard. Conclusion: The overall absorption of abacavir sulphate was more in the test formulation with respect to the reference product at the same dose. Hence the study concludes that abacavir sulphate mucoadhesive buccal films achieved prolonged muchoadhesion and improved bioavailability compared to the conventional formulation.

Rapamycin mitigates inflammation-mediated disc matrix homeostatic imbalance by inhibiting mTORC1 and inducing autophagy through Akt activation.

Low back pain is a global health problem that originated mainly from intervertebral disc degeneration (IDD). Autophagy, negatively regulated by the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, prevents metabolic and degenerative diseases by removing and recycling damaged cellular components. Despite growing evidence that autophagy occurs in the intervertebral disc, the regulation of disc cellular autophagy is still poorly understood. Annulus fibrosus (rAF) cell cultures derived from healthy female rabbit discs were used to test the effect of autophagy inhibition or activation on disc cell fate and matrix homeostasis. Specifically, different chemical inhibitors including rapamycin, 3-methyladenine, MK-2206, and PP242 were used to modulate activities of different proteins in the PI3K/Akt/mTOR signaling pathway to assess IL-1β-induced cellular senescence, apoptosis, and matrix homeostasis in rAF cells grown under nutrient-poor culture condition. Rapamycin, an inhibitor of mTOR complex 1 (mTORC1), reduced the phosphorylation of mTOR and its effector p70/S6K in rAF cell cultures. Rapamycin also induced autophagic flux as measured by increased expression of key autophagy markers, including LC3 puncta number, LC3-II expression, and cytoplasmic HMGB1 intensity and decreased p62/SQSTM1 expression. As expected, IL-1β stimulation promoted rAF cellular senescence, apoptosis, and matrix homeostatic imbalance with enhanced aggrecanolysis and MMP-3 and MMP-13 expression. Rapamycin treatment effectively mitigated IL-1β-mediated inflammatory stress changes, but these alleviating effects of rapamycin were abrogated by chemical inhibition of Akt and mTOR complex 2 (mTORC2). These findings suggest that rapamycin blunts adverse effects of inflammation on disc cells by inhibiting mTORC1 to induce autophagy through the PI3K/Akt/mTOR pathway that is dependent on Akt and mTORC2 activities. Hence, our findings identify autophagy, rapamycin, and PI3K/Akt/mTOR signaling as potential therapeutic targets for IDD treatment.

Intratympanic injections of emulsion-like dispersions to augment cinnarizine amount in a healthy rabbit inner ear model.

Aim: To investigate eutectic liquid-based emulsion-like dispersions for intratympanic injections to augment cinnarizine permeability across round window membrane in a healthy rabbit inner ear model.Methods: Two-tier systematic optimization was used to get the injection formula. The drug concentrations in perilymph and plasma were analyzed via. Ultra-performance liquid chromatography-tandem mass spectrometry method after 30-, 60-, 90- and 120-min post intratympanic injection time points in rabbits.Results: A shear-thinning behavior, immediate drug release (∼98.80%, 10min) and higher cell viability (>97.86%, 24h) were observed in dispersions. The cinnarizine level of 8168.57±1236.79ng/ml was observed in perilymph at 30min post intratympanic injection in rabbits.Conclusion: The emulsion-like dispersions can augment drug permeability through round window membrane.

Development of an LC-MS/MS technique and its validation for the determination of infigratinib in human K2EDTA plasma; Pharmacokinetics in healthy rabbits

A precise and linear liquid chromatography tandem mass spectrometry technique was developed for the estimation of infigratinib in human K2EDTA plasma. Chromatographic isolation of infigratinib and dasatinib was attained on orosil, 3 μm, C18, 150 × 4.6 mm stationary phase with a 0.8 ml/minute movable phase flow rate. The method was rectilinear in a concentration range of 1–1,640 ng/ml. Validation showed an r2 = 0.9997 and an equation of y = 0.0015x − 0.0063. The average accuracies of back-assessed concentrations for all quality controls (QCs) were between 96.34 and 100.76. At medium QC, high-QC, and low-QC concentrations, infigratinib had 98.14%, 96.36%, and 97.21% mean recoveries, respectively. Retention time %CV findings were ≤0.62 for the analyte and dasatinib, respectively. The developed method was successfully applied to the pharmacokinetic studies of infigratinib in healthy rabbits. The Cmax, Tmax, and T1/2, of the infigratinib tablets were 87.25 } 1.43 ng/ml, 6.0 } 0.03 hours, and 15.24 } 0.53 hours, respectively. AUC 0–∞ infinity for infigratinib tablets was 291.74 } 3.67 ng h/ml. The developed method was successfully validated and can be utilized for the assessment of infigratinib in biological matrices at industries, forensic laboratories, QC laboratories, and bioavailability studies.

Fractal Phototherapy in Maximizing Retina and Brain Plasticity.

The neuroplasticity potential is reduced with aging and impairs during neurodegenerative diseases and brain and visual system injuries. This limits the brain's capacity to repair the structure and dynamics of its activity after lesions. Maximization of neuroplasticity is necessary to provide the maximal CNS response to therapeutic intervention and adaptive reorganization of neuronal networks in patients with degenerative pathology and traumatic injury to restore the functional activity of the brain and retina.Considering the fractal geometry and dynamics of the healthy brain and the loss of fractality in neurodegenerative pathology, we suggest that the application of self-similar visual signals with a fractal temporal structure in the stimulation therapy can reactivate the adaptive neuroplasticity and enhance the effectiveness of neurorehabilitation. This proposition was tested in the recent studies. Patients with glaucoma had a statistically significant positive effect of fractal photic therapy on light sensitivity and the perimetric MD index, which shows that methods of fractal stimulation can be a novel nonpharmacological approach to neuroprotective therapy and neurorehabilitation. In healthy rabbits, it was demonstrated that a long-term course of photostimulation with fractal signals does not harm the electroretinogram (ERG) and retina structure. Rabbits with modeled retinal atrophy showed better dynamics of the ERG restoration during daily stimulation therapy for a week in comparison with the controls. Positive changes in the retinal function can indirectly suggest the activation of its adaptive plasticity and the high potential of stimulation therapy with fractal visual stimuli in a nonpharmacological neurorehabilitation, which requires further study.

Cellular experimental study and mechanism of surface modification of 3D printed titanium materials to modulate the sealing and antimicrobial properties of oral implants

Investigating the role of surface-modified 3D printed titanium implants in modulating oral soft tissue closure and antimicrobial properties. Eighteen 6-month-old healthy adult New Zealand White rabbits were selected as experimental animals, the left and right mandibular teeth of each experimental animal were randomly divided into two groups, and the bilateral first premolar teeth were extracted after general anesthesia, and one implant was implanted into each of the magnesium/zinc ionized surface-treated group (experimental group) and the surface-untreated group (control group), with a total of 36 implants, i.e., 18 implants for the experimental group and 18 implants for the control group. Bilateral mandibular samples from both groups were removed after 2 and 4 weeks of implantation to investigate the attachment and spreading of human gingival fibroblasts (HGFs) on the surface of the samples, their proliferative and migratory behaviors as well as the expression levels of related gene proteins (CoL-1 and TGF-β), and HE staining of the soft tissues of the samples and inflammatory cell counts. After 2 and 4 weeks of implantation, the experimental group’s HGFs adhesion and spreading were significantly better than that of the control group, the migration and proliferation of HGFs were significantly greater than that of the control group ( p &lt; .05), and the expression of CoL-1 and TGF-β genes was significantly higher than that of the control group ( p &lt; .05), and the inflammatory cell count was significantly smaller than that of the control group ( p &lt; .05). Surface modification by magnesium and zinc ions enhances the sealing performance and antimicrobial performance of 3D printed titanium implants in oral soft tissues, with significant effects.

Feasibility and safety of ultrasound-guided percutaneous transhepatic measurement of portal venous pressure.

The measurement of portal venous pressure (PVP) has been extensively studied, primarily through indirect methods. However, the potential of ultrasound-guided percutaneous transhepatic PVP measurement as a direct method has been largely unexplored. This study aimed to investigate the accuracy, safety, and feasibility of this approach. In vitro, the experiment aimed to select a needle that could accurately transmit pressure, had a small inner diameter and was suitable for liver puncture, and performed on 20 healthy New Zealand white rabbits. An ultrasound-guided percutaneous transhepatic portal vein puncture was undertaken to measure PVP. Additionally, free hepatic venous pressure (FHVP) and wedged hepatic venous pressure (WHVP) were measured under digital subtraction angiography (DSA). The correlation between the two methods was assessed. Enroll study participants from October 18, 2023 to November 11, 2023 with written informed consent. Five patients were measured the PVP under ultrasound guidance before surgery to determine the feasibility of this measurement method. There was no significant difference in the results obtained using 9 different types of needles (P > 0.05). This demonstrated a great repeatability (P < 0.05). The 22G chiba needle with small inner diameter, allowing for accurate pressure transmission and suitable for liver puncture, was utilized for percutaneous transhepatic PVP measurement. There were positive correlations between PVP and HVPG (r = 0.881), PVP and WHVP (r = 0.709), HVPG and WHVP (r = 0.729), IVCP and FHVP (r = 0.572). The PVP was accurately and safely measured in 5 patients with segmental hepatectomy. No complications could be identified during postoperative ultrasound. Percutaneous transhepatic portal venous puncture under ultrasound guidance is accurate, safe and feasible to measure portal venous pressure. This study has been registered in the Chinese Clinical Trial Registry with registration number ChiCTR2300076751.

Flap of the sternocephalicus muscle in the repair of a partial defect in the trachea of a rabbit (Oryctolagus cuniculus).

The current study aimed at evaluating the repair of a partial defect of the trachea with a muscle flap, an advanced technique that employs combined suture patterns. Sixteen healthy male New Zealand white rabbits were used as an experimental model. A partial defect in the trachea within the ventral region of the fourth to eighth tracheal ring was created. Subsequently, repair was initiated with a flap of the sternocephalicus muscle. The animals were divided into four groups for postoperative evaluation using clinical, tracheoscopic, and histopathological analyses. Each group was separated according to the time of euthanasia, programmed at interval of seven (G7), 15 (G15), 30 (G30), and 60 days (G60). One animal from the G60 group died, whereas the other animals had good surgical recovery without serious changes in the breathing pattern. The major clinical signs observed were stridor and coughing. Tracheoscopy revealed secretions in the tracheal lumen, exuberant granulation, and stenosis. Histopathological analysis showed growth of the ciliary respiratory epithelium at the flap site 30 days after implantation. Partial repair showed satisfactory results owing to the anatomical location of the muscle, adequate vascular support, and structural and physiological maintenance without serious changes in the respiratory system.

The influence of drugs containing polyhydroxy acids on metabolic processes and physiological vital signs of rabbits

The work is devoted to the use of polyhydroxy acids with antioxidant properties in rabbit breeding. The authors examined the effect of gluconolactone, used in the diet of animals, on metabolic processes and physiological indicators of the vital functions of rabbits. To raise healthy rabbits with high meat quality, balanced feeding is necessary. When there is an imbalance in feed rations, animals get sick more often and gain body weight more slowly. Rabbits, like other animals, can obtain antioxidants from plant foods, but their concentration may not be sufficient to provide full protection against oxidative stress. To stabilize feed rations, various biologically active additives are used to increase the efficiency of raising animals and improve productivity indicators. Based on the studies conducted (using the example of gluconolactone), the authors showed the therapeutic significance and feasibility of including supplements containing polyhydroxy acids in the diet of rabbits.

Effect of carboxymethyl cellulose, icodextrin and hyaluronic acid solutions on postoperative intraabdominal adhesion formation in rabbits and the role of cytokines in intraabdominal adhesion formation

In this study, the aim was to investigate the effects of 1% CMC, 4% ICO and 0.4% HA solutions in preventing postoperative IAs and their contribution to peritoneal wound healing, as well as the relationship of cytokines with the formation of postoperative IAs in rabbits. The material of the study consisted of 32 healthy rabbits. Rabbits underwent median laparotomy following general anesthesia. Serosal abraded was created at the antimesenteric border of the cecum. Next, a 3 × 2 cm peritoneum was excised on the right abdominal wall and the defect was closed using with a 2/0 silk suture. The rabbits were randomly assigned to either of the following four treatment groups: CNT (0.9% NaCl), ICO (4% icodextrin), HA (0.4% hyaluronic acid) and CMC (1% carboxymethyl cellulose). Both cecum and peritoneal surfaces were treated with 20 ml each of treatment solutions. On the 7th postoperative day, the rabbits were euthanized with a lethal dose of sodium pentobarbital and the degree of adhesion was evaluated. Samples taken from the peritoneal defect were examined histopathologically and tissue hydroxyproline levels were measured. Serum TNF-α, IL-1 and IL-6 levels were measured from blood samples taken before the surgery and at 1, 6, 24 and 48 hours after the surgery. It was observed that the adhesion grade in the HA group (p &lt; 0.05) and CMC group (p &lt; 0.01) was significantly lower than the control group. Although peritoneal tissue hydroxyproline levels were lower in the other groups compared to the control group, they were not statistically significant (p &gt; 0.05). In rabbits with adhesion formation, it was determined that TNF-α levels increased at the 6th postoperative hour (p &lt; 0.05), and IL-6 levels increased at the 6th, 24th and 48th postoperative hours (p &lt; 0.001) compared to preoperative. In this study, treating tissues with 0.4% HA and 1% CMC solutions suppressed peritoneal inflammation, and this resulted in an increase in the levels of proinflammatory cytokines TNF-α and IL-6. It has been determined that the application of these solutions reduces postoperative adhesion formation. It was concluded that TNF-α and especially IL-6, which are proinflammatory cytokines, can be a non-invasive biomarker in determining postoperative IA formation and evaluating the adhesive process.

Effects of Laurus nobilis Leaf Extract on Healing of Experimentally Induced Wounds in Rabbits.

Wound or injury can be defined as partial or complete separation of the skin, while the healing of the wounds is defined as the sequences of processes by which the skin heals and returns to its normal appearance. This study aims to evaluate the efficacy of Laurus nobilis leaf extracts on the healing of open wounds in rabbits. Twenty-four healthy rabbits were used, divided randomly into control and treated groups, each consisting of 12 rabbits. The rabbits were caused to experience circular wound defects (2.5 cm) in diameter. All animals in the control (C) group were left without treatment while those in the Laurus nobilis leaf extract group were treated with drops of the aqueous extract of Laurus nobilis in a dose of 200 mg/kg per day for 20 days. The results of macroscopic observation revealed that all animals in both groups showed equitable viability and good appetite, no mortality occurred, and no signs of infection. In the group with the Laurus nobilis extract, we noticed a significant improvement in wound-healing activity and a reduction in the wound area at p ≤ 0.05 compared with the C group. Histopathological results at the end of the study show that the thick epidermal layer covers a mass of granulation with congested blood vessels and the dermis transforms into a denser layer gradually due to the improvements of the cellularity in the C group and also revealed a well-formed skin appearance, widespread of collagen, and fibrosis within the dermis with an appearance near the normal dermis in the group treated with Laurus nobilis leaf extract. In conclusion, the results confirmed that using Laurus nobilis methanolic extract solution in a daily dose of 200 mg/kg promotes healing of open wounds in rabbits.

Existence of Quantum Pharmacology in Sartans: Evidence in Isolated Rabbit Iliac Arteries.

Quantum pharmacology introduces theoretical models to describe the possibility of ultra-high dilutions to produce biological effects, which may help to explain the placebo effect observed in hypertensive clinical trials. To determine this within physiology and to evaluate novel ARBs, we tested the ability of known angiotensin II receptor blockers (ARBs) (candesartan and telmisartan) used to treat hypertension and other cardiovascular diseases, as well as novel ARBs (benzimidazole-N-biphenyl tetrazole (ACC519T), benzimidazole-bis-N,N'-biphenyl tetrazole (ACC519T(2)) and 4-butyl-N,N0-bis[[20-2Htetrazol-5-yl)biphenyl-4-yl]methyl)imidazolium bromide (BV6(K+)2), and nirmatrelvir (the active ingredient in Paxlovid) to modulate vascular contraction in iliac rings from healthy male New Zealand White rabbits in responses to various vasopressors (angiotensin A, angiotensin II and phenylephrine). Additionally, the hemodynamic effect of ACC519T and telmisartan on mean arterial pressure in conscious rabbits was determined, while the ex vivo ability of BV6(K+)2 to activate angiotensin-converting enzyme-2 (ACE2) was also investigated. We show that commercially available and novel ARBs can modulate contraction responses at ultra-high dilutions to different vasopressors. ACC519T produced a dose-dependent reduction in rabbit mean arterial pressure while BV6(K+)2 significantly increased ACE2 metabolism. The ability of ARBs to inhibit contraction responses even at ultra-low concentrations provides evidence of the existence of quantum pharmacology. Furthermore, the ability of ACC519T and BV6(K+)2 to modulate blood pressure and ACE2 activity, respectively, indicates their therapeutic potential against hypertension.

COMPARATIVE EFFECTS OF THREE PLANT PROTEIN CAKES ON PERFORMANCE, NUTRIENT DIGESTIBILITY, HAEMATOLOGY, SERUM BIOCHEMISTRY AND PRODUCTION ECONOMICS OF WEANER RABBITS

This research was conducted to compare the effects of feeding three plant protein cakes, groundnut cake (GNC), cottonseed cake (CSC), and palm kernel cake (PKC) on performance, nutrient digestibility, haematology, serum biochemistry, and production economics of weaner rabbits. Twenty-four six weeks old, mixed-breed rabbits of both sexes were allotted into three groups randomly containing eight rabbits each. The treatment groups (T1, T2, and T3) were fed for five weeks on three different diets containing GNC, CSC, and PKC as protein sources respectively. Data generated were analyzed using one-way ANOVA. It was revealed that majority of the performance parameters were not affected (p&gt;0.05) except final body weight which differed significantly (p&lt;0.05) across the treatment groups. The ash contents of the diets also varied significantly (p&lt;0.05) amid other parameters of nutrient digestibility. The diets had no adverse effects on hematological and biochemical parameters, but total bilirubin, creatinine, and sodium were affected (p&lt;0.05). This study also revealed that CSC compared favorably with GNC in terms of growth performance and economics of rabbit production, while PKC had poor economic values for production. It was therefore suggested that the three cakes are non-toxic to the muscle, kidneys, and liver of rabbits at 17.43% inclusion level. This indicates that groundnut cake, cottonseed cake and palm kernel cake can be used as sources of protein in the diet of weaner rabbits without affecting the blood and serum biochemical parameters of weaner rabbits because the enzyme levels continued within the reference range of healthy rabbits.

PROTECTIVE EFFECTS OF GRAPE SEED EXTRACT (VITIS VINIFERA) AGAINST CISPLATIN-INDUCED LIVER DAMAGE IN RABBITS. (HISTOLOGICAL AND HISTOPATHOLOGICAL STUDY)

Cisplatin is a chemotherapeutic drug used in the treatment of various cancer types. It can be considered a double-edged sword. It is a potent anticancer agent at the same time has toxic effect on various tissues as it causes hepatotoxicity. It was determined to cause liver toxicity and to weaken the antioxidant defense systems in liver. A decrease in antioxidant enzymes resulted from cisplatin induced tissue toxicity. Moreover, the development of therapies to prevent the appearance of cisplatin- induced tissue toxicities has focused on administration of antioxidants along with cisplatin treatment. The grape seeds exhibit a broad spectrum of pharmacological properties against oxidative stress. Therefore, the aim of present study was designed to investigate the protective effects of grape seed extract on the liver damage in cisplatin treated rabbits. Twenty seven healthy rabbits of local mixed breed were selected, divided into three equal groups, the first group (CON group) served as control and received a single intraperitoneal injection of normal saline solution once per week for 6 weeks; the second group (CIS group) were treated with therapeutic dose of cisplatin intraperitoneally once per week for six weeks; the third group (CIS+GSE group) served as protective group and was concomitantly treated with grape seeds extract by oral gavages and cisplatin injection intraperitoneally once per week for six successive weeks. Administration of grape seeds extract by oral gavages starting from the first day of the experiment for 6 consecutive days before and 6 consecutive days after the cisplatin injection and continued daily for 6 weeks. The histopathological findings present in current study showed that cisplatin toxicity produced significant structural changes in the liver of CIS group, cisplatin treated group, in the form of prominent disorganized architecture and loss of liver lobulation, distortion of the arrangement of parenchyma of the liver, loss of radial arrangement of sinusoids from the central vein of the liver, Dilatation and congestion of central veins, sinusoids and portal traids, degenerative changes in hepatocytes and pyknotic nuclei indicating necrosis. Marked vacuolar degeneration mainly hydropic ballooning degeneration and hyper activation of Kupffer cells and inflammatory cellular infiltrations were also observed. This finding reflected the cytotoxic effects of cisplatin in hepatic tissue. While, in the sections from the liver of animals received therapeutic dose of cisplatin and treated by grape seed extract, group (CIS+GSE) clearly showed that there was a significant alleviated hepatotoxicity, since histopathological changes were markedly less pronounced compared to animals treated with cisplatin alone. Therefore, and based on our findings, the grape seed extract contributes significantly to the improvement of histological alterations in rabbit liver caused by cisplatin.