Search Results (213)

Pomegranate peel, a rich agro-industrial by-product, contains abundant phenolic compounds with strong antioxidant and antimicrobial properties. However, the low stability and bioavailability of these compounds limit their efficacy in animal nutrition. This study investigated the effects of pomegranate peel phenolic extract (PE), either in raw form (PE300) or nano-encapsulated using gum–gelatin nano-capsules (NPE300), on health and growth parameters in newly weaned rabbits. Fifty-four male rabbits (40 days old) were assigned to three treatment groups: PE0 (control), PE300 (300 mg PE/L drinking water), and NPE300 (300 mg nano-encapsulated PE/L drinking water). Over six weeks, growth performance, hematological and immunological profiles, antioxidant status, microbial populations, and carcass traits were evaluated. NPE300 treatment demonstrated superior antimicrobial activity in vitro, with larger inhibition zones against all tested pathogens compared to PE300. In vivo, NPE300 significantly improved body weight gain (945.8 g) and feed efficiency, while also enhancing immune function, evidenced by higher white and red blood cell counts, phagocytic activity, and increased plasma IgG and IgM levels. Antioxidant markers showed that NPE300 significantly reduced malondialdehyde levels and tended to improve total antioxidant capacity. Furthermore, intestinal Clostridia counts were reduced, and beneficial microflora significantly increased in the NPE300 group. Carcass weight with edible parts, fur weight, kidney weight, and cecum length were also elevated under NPE300 treatment. In conclusion, nanoencapsulation of PE using gum–gelatin carriers enhanced its bio-efficacy, supporting better redox balance, immunity, gut health, and growth performance in rabbits. These findings support the application of nano-encapsulated PE as a promising natural growth promoter in rabbit production. Full article

Kaempferitrin (KAE) is a natural flavonol dirhamnopyranoside with various pharmacological activities, isolated from the antithrombotic fraction of Celastrus orbiculatus Thunb. This study aimed to investigate the antithrombotic activity and “effective forms” of KAE. The results showed that KAE significantly prolonged rabbit plasma recalcification time in vitro. In the FeCl₃-induced rat arterial thrombosis model, KAE demonstrated antithrombotic effects by inhibiting coagulation, platelet aggregation, and fibrinolysis, with a lesser risk of bleeding compared to aspirin. KAE was orally administered to rats, and a total of 192 metabolites were characterized. These included 25 phase I metabolites, 8 hydroxylated and methylated metabolites, 57 sulfated metabolites, 74 glucuronidated metabolites, 26 sulfated and glucuronidated metabolites, and 2 glycosylated metabolites. Twenty-eight compounds were considered the in vivo “effective forms” of KAE for their antithrombotic activity. Network pharmacology, molecular docking, and molecular dynamics simulations collectively predict that these “effective forms” may exert antithrombotic effects by suppressing the SRC/PI3K/AKT pathway. This study provides a foundation for a better understanding of the in vivo “effective forms” and mechanisms underlying KAE’s antithrombotic activity, which is essential for understanding of “hexue” traditional efficacy of C. orbiculatus. Full article

Thymol gastro-resistant self-emulsifying pellets were used to achieve thymol targeted release on the side of the intestine with the most intensive absorption to enhance its oral bioavailability. Forty-eight rabbits (35 d of age) were divided into two groups fed with a standard diet containing gastro-resistant enteric pellets (control, CG; without thymol, initial live weight 1350.0 ± 18.0, and experimental, EG; with thymol 250 mg/kg, initial live weight 1352.0 ± 19.9 g). The experiment lasted 28 days: thymol was administered for 21 days and then withdrawn for 7 days. Thymol was significantly higher in duodenal wall (DW) than in plasma during both periods (p = 0.0053, p < 0.0001). Significant correlation was established between thymol concentration in plasma and DW during its application (r_s = 0.9333, p < 0.001). Thymol was below the limit of quantitation in plasma, spleen and muscle only after its withdrawal, and its significantly higher concentration in kidney and fat than in plasma (p = 0.0182, p = 0.0003) and muscle (p = 0.0236, p = 0.0004) indicates its efficient accumulation. Thymol in gastro-resistant form prevented its degradation due to adverse conditions in the stomach and ensured its release at the site of greatest absorption in the small intestine. Full article

Intervertebral disc degeneration is a leading cause of chronic back pain, with existing treatments focusing on symptom management rather than true tissue repair. Cellular therapies—such as platelet-rich plasma (PRP), autologous chondrocytes, and mesenchymal stem cells (MSCs)—have emerged as promising strategies for disc regeneration. In this study, fifteen New Zealand white rabbits underwent fluoroscopy-guided needle puncture of the L4-L5 discs and were allocated to receive PRP alone, PRP-chondrocytes, or PRP-MSCs eight weeks later, while the L3-L4 disc served as a healthy internal control. At 16 weeks post-injury, histological scoring revealed significant improvements in annular integrity, cellularity, and matrix composition in all treated groups compared with untreated lesions, with the greatest gains observed in the PRP-chondrocytes arm, intermediate effects with PRP-MSCs, and more modest changes with PRP alone. Complementary RT-qPCR analysis of COL2A1 and COL10A1 expression confirmed a shift toward a more regenerative phenotype, marked by enhanced COL2A1 and reduced COL10A1 levels, which was most pronounced in the PRP-chondrocytes arm. Despite these advances, none of the interventions fully restored the healthy disc architecture, underscoring the complexity of disc repair. These findings support the potential of combining PRP with chondrocytes or MSCs for intervertebral disc regeneration and demonstrate the need for further optimization of cell doses, PRP formulations, and delivery protocols before clinical translation. Full article

This study evaluated the effects of dietary cannabidiol (CBD) supplementation on behavior, blood parameters, oxidative status, metabolomic profile, and the fatty acid composition of meat and liver in rabbits. A total of 42 New Zealand White × California rabbits (60 days old; 1:1 sex ratio; average weight 1621.3 ± 46.2 g) were randomly assigned to two groups (a control group, CTRL, and a CBD group, n = 21 each). Both groups received the same commercial diet, with the CBD group additionally supplemented with 0.1 mL of cannabis extract in coconut oil, corresponding to 10 mg CBD/animal/day. At 92 days of age, rabbits were slaughtered, and samples were collected for analyses. Results showed that CBD supplementation significantly improved body weight gain, reduced plasma triglyceride levels, and enhanced oxidative status. Behavioral observations indicated increased motor and grooming activities in CBD-supplemented animals, suggesting enhanced psychological well-being. The fatty acid profile of meat and liver was not significantly altered by CBD supplementation. Overall, dietary CBD demonstrated the potential to positively influence physiological and behavioral responses, representing a promising strategy to enhance animal welfare and productivity in rabbit farming. Although no adverse effects on lipid profiles were observed, further studies are warranted to explore CBD’s role in lipid metabolism and cholesterol regulation. Full article

Artificial insemination (AI) in rabbits depends largely on chilled semen storage, but the physiological responses to chilling and associated biochemical changes in seminal plasma (SP) remain poorly understood, particularly across breeds. This study aimed to compare the semen preservation capacity of Algerian local population (LAP) and New Zealand White (NZW) rabbits and to explore the relationship between SP oxidative stress biomarkers and sperm traits during 72 h of chilled storage at 5 °C. Semen pools (nine/breed) were evaluated at 0, 4, 24, 48, and 72 h for motility, viability, and acrosome status. Oxidative stress markers were also assessed in the SP, including malondialdehyde (MDA), reactive oxygen metabolites (ROMs), superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT). LAP sperm showed higher motility (p < 0.001) and viability (p < 0.05), particularly between 4 h and 48 h, and exhibited a lower rate of acrosome reaction (p < 0.001) from 48 h to 72 h. Lower SOD and higher CAT activity in LAP (p < 0.001), correlated with MDA and acrosome status, respectively, may reflect a more balanced antioxidant response. Lipid peroxidation did not appear to be the main factor driving sperm deterioration (p > 0.05). These results demonstrate that LAP rabbits exhibit better resilience to chilled storage compared to NZW and highlight the potential value of CAT and SOD activities as indicators of sperm resilience during chilled storage. Further studies are required to validate and extend these findings, with the aim of improving semen preservation strategies. Full article

Platelet-rich plasma (PRP) is widely applied in veterinary regenerative medicine due to its rich composition of growth factors that promote tissue repair. However, the direct pro-angiogenic function of canine PRP (cPRP) has not been thoroughly validated through controlled in vitro and in vivo experimentation. Human umbilical vein endothelial cells (HUVECs) were used to assess cell proliferation, migration, and tube formation after exposure to cPRP. In addition, a rabbit corneal micropocket assay was employed to evaluate in vivo angiogenic responses. Treatment with 20% cPRP significantly enhanced HUVEC proliferation and migration and induced robust tube formation. In the in vivo model, we observed dose-dependent neovascularization, with the earliest vascular sprouting seen on day 1 in the 40% group. Both models consistently demonstrated that cPRP stimulates vascular development in a concentration-dependent manner. This study provides novel evidence of cPRP’s capacity to induce neovascularization, supporting its therapeutic value for treating nonhealing wounds in dogs, especially in cases involving chronic inflammation, aging, or immune dysregulation. These findings offer a scientific foundation for the broader clinical application of cPRP in veterinary regenerative practice. Full article

Propolis is a natural resinous substance produced by honeybees that has many biological activities. For thousands of years, it has been widely used as a dietary supplement and traditional medicine to treat a variety of ailments due to its antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, and wound-healing properties. Nutritional supplements and foods may interact with drugs both pharmacodynamically and pharmacokinetically, which could raise clinical concerns. Background/Objectives: This study aimed to investigate the effect of propolis on the plasma disposition of enrofloxacin and to assess the potential pharmacokinetic interaction in rabbits. Methods: In this study, enrofloxacin was applied per os (20 mg/kg) and IM (10 mg/kg) and with propolis (100 mg resin/kg) administration in four groups of rabbits (each of six individuals). Heparinized blood samples were collected at 0, 0.1, 0.3, 0.5, 1, 2, 4, 8, 12, and 24 h post-administration. HPLC-FL was used to analyze the plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin following liquid–liquid phase extraction, i.e., protein precipitation with acetonitrile and partitioning with sodium sulfate. Results: The results revealed that propolis coadministration significantly affected the plasma disposition of enrofloxacin and its active metabolite after both per os and intramuscular administration routes. Significantly greater AUC (48.91 ± 11.53 vs. 26.11 ± 12.44 µg.h/mL), as well as longer T_1/2λz (11.75 ± 3.20 vs. 5.93 ± 2.51 h) and MRT (17.26 ± 4.55 vs. 8.96 ± 3.82 h) values of enrofloxacin and its metabolite ciprofloxacin, were observed after the coadministration of propolis compared to enrofloxacin alone following both per os and IM routes in rabbits. Conclusions: The concurrent use of propolis and prescription medications may prolong the half-life (T_1/2λz) and increase the systemic availability of chronically used drugs with narrow therapeutic indices. The repeated use of drugs such as antibiotics, heart medications, and antidepressants, or drugs with a narrow therapeutic index such as antineoplastic and anticoagulant agents, can cause toxic effects by raising blood plasma levels. Considering the varied metabolism of rabbits and humans, further validation of this study may require thorough clinical trials in humans. Full article

Osteopontin (OPN) is a protein that plays many essential functions in the human body. It is present in most tissues and body fluids. OPN, among other things, participates in wound healing, the formation and remodeling of bone, immune response, inflammation, angiogenesis, and tumor formation. A new analytical method, based on SPRi (surface plasmon resonance imaging) biosensors, has been developed to determine osteopontin in biological fluids. OPN was captured from a solution by an immobilized antibody (mouse or rabbit), a bioreceptor in the SPRi sensor. A separate validation process was carried out for each antibody used. The LOD and LOQ values obtained for the biosensor with mouse antibody were 0.014 ng mL⁻¹ and 0.043 ng mL⁻¹, respectively, and those obtained for the biosensor with rabbit antibody were 0.018 ng mL⁻¹ and 0.055 ng mL⁻¹, respectively. The response ranges of both biosensors were in a similar range: 0.05–1.00 ng mL⁻¹. OPN was determined in blood plasma to demonstrate the sensor potential, showing good agreement with the data obtained using an ELISA test and reported in the literature. The presented method is characterized by ease and speed of measurement, and the process does not require special preparation of samples. Full article

Graphene oxide (GO), owing to its extraordinary application prospects in biomedicine, is attracting growing research attention. However, the biosafety and blood compatibility of GO required for its clearance for use in clinical trials remain elusive. Therefore, we studied the mutagenic properties of GO as well as its cell toxicity and blood compatibility. Prior to biological experiments, we assessed the structural organization of GO using dynamic light scattering and microscopic visualization methods. The results of both the Ames mutagenicity test performed on Salmonella enterica serovar Typhimurium TA98 and TA102 strains and the cytotoxicity test on noncancerous, immortalized human keratinocytes revealed no mutagenic or toxic effects of GO. Simultaneously, GO reduced the viability of the MelJuSo human melanoma cell line. A blood compatibility assay revealed that a concentration of 10 μg/mL was critical for GO biosafety, as greater concentrations induced diverse side effects. Specifically, GO disrupts erythrocytes’ membranes in the dose-dependent manner. Moreover, GO at higher concentrations both inhibited the process of ADP (a physiological platelet agonist)-induced cell aggregation and affected their disaggregation process in platelet-rich plasma. However, in the blood clotting assessment, GO showed no effects on the activated partial thromboplastin time, prothrombin time, or thrombin time of the platelet-poor plasma. The obtained results clearly indicate that the relationship between the GO preparation method, its size, and concentration and biosafety must be cautiously monitored in the context of further possible biomedical applications. Full article

Background/Objectives: Exudative age-related macular degeneration (AMD) is a disease of choroidal neovascularization that causes blindness. Current treatments to preserve vision in this prevalent and blinding condition are repeat intraocular injections of anti-vascular endothelial growth factor medicines for a patient’s lifetime to preserve and prevent vision loss leading to blindness. Rifampicin, a small-molecule antibiotic, has previously been reported to exhibit anti-angiogenic properties and a topical safety profile that is well-tolerated. Based on this evidence, we investigated the feasibility of formulating rifamycin as an ophthalmic drop capable of delivering therapeutic concentrations to the posterior segment of the eye. Methods: Inhibition of neovascularization by administration of rifampicin was analyzed in the rat oxygen-induced retinopathy (OIR) and mouse laser-induced choroidal neovascularization (CNV) models. Pharmacokinetic (PK) studies were conducted in mice, rats, and rabbits by dosing various formulations containing rifampicin, and the compound was quantified by LC/MS analysis. Results: Results from dose escalation studies in the mouse laser-induced CNV model suggested the minimum effective dose of rifampicin required for inhibiting neovascularization in subretinal tissues to be 0.7 mg/kg, which is substantially lower than the 20 mg/kg dosage approved for infectious disease treatments. The previous studies did not report the minimum effective dose in the anti-angiogenesis effects. The effective area under the concentration-time curve (AUC) in the sub-retina was evaluated as 0.27 h·ng/mg. In rabbits, rifampicin was delivered to the sub-retina by a single topical application of various formulations in a dose-dependent manner. The topical application of the formulations containing 1% rifampicin, which was well-tolerated in clinical trials previously reported for ocular trachoma, achieved subretinal delivery approximately 2–32 times greater than the effective AUC. Plasma exposure of the compound by the topical application was evaluated to range approximately 0.5–10 ng/mL. Conclusions: Rifampicin was delivered to the sub-retina in rabbits with an efficiency greater than the effective dose required for inhibiting neovascularization. Limited amounts of plasma exposure by the topical application were detected. These results suggested the therapeutic potential of the rifampicin formulations for the topical treatment of exudative macular degeneration. Full article

Vitexin and isovitexin are natural flavone C-glucosides that have numerous benefits for human health. However, their low oral bioavailability and poor gastrointestinal absorption dramatically restrict their potential medicinal uses. To overcome this challenge, chitosan-coated alginate microcapsules were prepared for intragastrical administration to rabbits. An LC-MS/MS method was developed and validated for the simultaneous determination of vitexin and isovitexin in the plasma of treated rabbits, using salicylic acid as the internal standard. Raw rabbit plasma samples were deproteinized using acetonitrile as a precipitation agent. Chromatographic separation was performed on a reversed-phase C18 column (100 mm × 4.6 mm, 3.5 µm), with an isocratic mobile solvent system comprising methanol and 0.1% acetic acid (40:60) as the mobile phase. All the analytes and the internal standard were ionized on a triple quadrupole mass spectrometer and electrospray ionization, operating in negative mode and multiple reaction monitoring. The analytical approach developed underwent validation in terms of system suitability, specificity, selectivity, LLOQ of 2 ng/mL, linearity (2.0–200 ng/mL, R² > 0.99), accuracy (the intra- and inter-day from 94 to 110% with the relative standard deviations no more than 8.7%, precision with the recoveries from 97% to 102%, matrix effect (90–100%), carry-over, dilution integrity (2 times), and stability at room and frozen temperature for up to 1 month, and all the parameters met FDA and EMA requirements for bioanalytical methods. The validated procedure was applied to measure the absorption of vitexin and isovitexin from encapsulated extracts in a pilot pharmacokinetic study on rabbit plasma. Compared to the raw traditional extracts, the microcapsules enhanced the bioavailability of vi-texin and isovitexin regarding C_max and AUC values. Full article

Lipopolysaccharide (LPS)-induced inflammation impairs sperm function; however, its impact on ejaculated rabbit sperm remains unexplored. This dose-response study aims to determine the LPS concentration that negatively affects sperm motility in vitro, while also providing the first identification of TLR4 localization on rabbit spermatozoa. Additionally, it evaluates malondialdehyde (MDA) levels in seminal plasma as an indicator of oxidative stress. Sperm motility was analyzed using computer-assisted sperm analysis (CASA) after incubation with increasing LPS concentrations (0, 50, 100, 200, 400, 600, and 800 µg/mL) at multiple time points (0, 1, 2, and 4 h). LPS doses ≥ 400 µg/mL significantly reduced progressive and non-progressive motility, as well as curvilinear velocity (all p < 0.001), while increasing the proportion of static spermatozoa (p < 0.05). Receiver operating characteristic (ROC) analysis identified 300 µg/mL as the threshold dose for motility decline. Immunofluorescence revealed TLR4 localization in the midpiece of sperm tails, with weak labeling in control samples and a marked increase after 4 h of incubation with 400 μg/mL LPS. MDA levels were assessed using the thiobarbituric acid reactive substances (TBARS) assay with a colorimetric kit, showing no significant effect of LPS treatment. No correlation was found between MDA and other semen parameters. ccThese findings identify TLR4 on rabbit sperm for the first time and establish a threshold LPS dose for future in vitro studies. Full article

A divergent selection for resilience was carried out in rabbits over 12 generations. The selection criterion was increased (the HO line) and decreased litter size variability at birth (the HE line). The HO line (more resilient) shows higher litter size than the HE line (less resilient). The HO line sows higher litter size and embryo development than the HE line. The aim of this work is to investigate the plasma organic acid profile in both lines at mating and early gestation in order to analyze the effect of selection by resilience in the ovulation rate and early gestation. A total of 19 and 18 nonlactating multiparous females from the HE and HO lines were used. The ovulation rate, normal embryos, and percentage of compacted morulae at 72 h post-coitum (hpc) were studied, and blood samples were obtained at mating and 72 hpc. The organic profile was determined by HPLC. Bayesian methodology was used for statistical analysis. The HE line had 1.5% fewer normal embryos and 12.3% fewer compacted morulae than the HO line. The ovulation rate was similar in both lines. α-ketoglutaric acid and cis-aconitic acid were higher in the HE line than in the HO line. Citric acid, lactic acid, and pyruvic acid were higher at mating than at early gestation. In conclusion, the lower efficiency in the utilization of energy sources in the HE line could explain the reduced embryo production observed. The organic profile varies depending on the reproductive state in the female. Full article

Cryopreservation is a widely used method for the long-term preservation of reproductive or somatic cells. It is known that this storage method may negatively affect cell viability, proliferation, differentiation, etc. However, there is a lack of information about whether cryostorage can alter the content of intracellular minerals. Therefore, we focused this study on the analysis of the mineral composition of living cells before and after long-term cold storage. Briefly, three different primary cell lines were established from rabbits as follows: endothelial progenitor cells from peripheral blood (EPCs), endothelial progenitor cells from bone marrow (BEPCs), and mesenchymal stem cells from adipose tissue (AT-MSCs), which were cultured until passage 3 prior to cryopreservation in liquid nitrogen. Samples from freshly cultured and frozen–thawed cells were mineralized and analyzed using inductively coupled plasma-optical emission spectroscopy (ICP-OES) for the content of minerals (macro: Ca, Na, K, and Mg, and micro: Zn, Fe, Cu, Al, Co, Mn, Sr, and Ni). After cryopreservation, we found significantly decreased content of K in frozen–thawed EPCs (p < 0.01) and BEPCs (p < 0.0001) and Ca in AT-MSCs (p < 0.05), while Na was increased in frozen–thawed BEPCs (p < 0.05). Concentrations of Fe and Al were reduced significantly in frozen–thawed EPCs (both p < 0.0001) and AT-MSCs (p < 0.001 and p < 0.0001, respectively). On the contrary, Fe and Al were elevated in frozen–thawed BEPCs (p < 0.0001 and p < 0.01, respectively) together with Ni (p < 0.0001). In addition, decreased Zn (p < 0.05) was observed in cryopreserved AT-MSCs. In conclusion, the ICP-OES technique might be used to analyze the basic elemental composition of animal cells in fresh or frozen–thawed conditions. Nevertheless, additional studies are needed to reveal the possible impact of cryopreservation on cell fate by changing the content of intracellular minerals. Full article