Insights into growth-promoting, anti-inflammatory, immunostimulant, and antibacterial activities of Toldin CRD as a novel phytobiotic in broiler chickens experimentally infected with Mycoplasma gallisepticum.

Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) leads to impaired broiler growth performance and significant economic losses worldwide. The utilization of essential oils (EOs) as natural alternatives to antibiotics to control CRD outbreaks is not completely clarified yet. Thus, we investigated the effect of a commercial EOs mixture (toldin CRD), in comparison to tilmicosin antibiotic, on the clinical observations, growth performance, immunity, digestive enzymes, gut barrier functions, and bacterial loads in broilers experimentally infected with MG. A total of 400 one-day-old broiler chicks were assigned into four groups; negative control (NC), positive control (PC), tilmicosin, and toldin CRD treated groups. All groups except NC were experimentally infected with MG at 14 d of age. Our data showed that birds treated with toldin CRD showed significant enhancement in the body weight gain (BWG) and feed conversion ratio (FCR) (P = 0.001 each) over the whole experimental period. Likely, improved digestibility and intestinal barrier functions in the toldin CRD treated group was evidenced by the significant upregulation (P < 0.05) of cholecystokinin (CCK), alpha 2A amylase (AMY2A), pancreatic lipase (PNLIP), junctional adhesion molecule-2 (JAM-2), occludin, and mucin-2 (MUC-2) genes. Moreover, toldin CRD exhibited immunostimulant and ant-inflammatory activities via significant downregulation (P < 0.05) of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 genes, significant reduction of lysozyme (LYZ), myeloperoxidase (MPO), and nitric oxide (NO) levels (P = 0.03, 0.02, and 0.001, respectively) and significant increase in the immunoglobulin G (IgG) level (P = 0.03). Notably, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR) results showed prominent reductions (P < 0.05) in the levels of MG antigens and MG loads in the toldin CRD treated group, which were evidenced by relieving the clinical picture of MG experimental infection. In conclusion, we recommend the utilization of toldin CRD as a potential candidate for controlling MG infection in broiler chickens.

Therapeutic potentials of aivlosin and/or zinc oxide nanoparticles against Mycoplasma gallisepticum and/or Ornithobacterium rhinotracheale with a special reference to the effect of zinc oxide nanoparticles on aivlosin tissue residues: an in vivo approach.

Respiratory diseases inflicted by Mycoplasma gallisepticum (MG) and Ornithobacterium rhinotracheale (ORT) cause severe economic losses and great burden to the poultry industry worldwide. Therefore, the current study was planned to assess the efficacy of aivlosin alone or in combination with zinc oxide nanoparticles (ZnO-NPs) in the treatment of experimental MG and/or ORT infections in broilers. Moreover, we also aimed to evaluate the role of ZnO-NPs on aivlosin residues in broiler tissues. A total of 1,440 Cobb chicks were allocated into 6 groups. At 14 d of age, chickens of groups 1 and 3 were experimentally infected with MG intratracheally and 6 d later, chickens of groups 2 and 3 were infected occulonasaly with ORT. Groups 1, 2, and 3 were divided into 4 subgroups; birds in subgroups 1, 2, and 3 were treated with aivlosin (A), ZnO-NPs (Z), and A/Z, respectively, while those in subgroups 4 was left without treatments. Moreover, groups 4 and 5 were kept noninfected and treated with aivlosin alone or in combination with ZnO-NPs, respectively. Finally, group 6 was kept as a negative control. The current results showed that the recovery from respiratory diseases caused by MG and/or ORT infections was most successful after treatment with A/Z in combination. Consequently, clinical signs, mortality rates, postmortem lesions of the respiratory organs, histopathological lesions of liver, trachea and lung and tracheal MG and ORT counts were significantly (P < 0.05) reduced following A/Z treatment. Taken together, high performance liquid chromatography analysis revealed that ZnO-NPs decreased the aivlosin residues in liver, muscle and skin of healthy and infected chickens. Based on these results, it could be concluded that aivlosin/ZnO-NPs therapy is a valuable approach for controlling MG and/or ORT infections in boilers.

Pharmacokinetic/Pharmacodynamic Modeling of Spiramycin against Mycoplasma synoviae in Chickens.

This research aimed to assess the pharmacokinetics/pharmacodynamics (PK/PD) and tissue residues of spiramycin in chickens. The PK of spiramycin were determined in 12 chickens using a parallel study design in which each group of chickens (n = 6) received a single dose of spiramycin at 17 mg/kg intravenously (IV) or orally. Plasma samples were collected at assigned times for up to 48 h to measure spiramycin concentrations. Additionally, a tissue depletion study was performed in 42 chickens receiving spiramycin at 17 mg/kg/day orally for 7 days. The area under the plasma concentration-time curve values were 29.94 ± 4.74 and 23.11 ± 1.83 µg*h/mL after IV and oral administrations, respectively. The oral bioavailability was 77.18%. The computed withdrawal periods of spiramycin were 11, 10, and 7 days for liver, muscle, and skin and fat, respectively. The minimum inhibitory concentration for spiramycin against Mycoplasma synoviae (M. synoviae) strain 1853 was 0.0625 µg/mL. Using the PK/PD integration, the appropriate oral dose of spiramycin against M. synoviae was estimated to be 15.6 mg/kg. Thus, we recommend an oral dose of 15.6 mg spiramycin/kg against M. synoviae in chickens and a withdrawal period of 11 days following oral treatment with 17 mg spiramycin/kg/day for 7 days.

Cinnamon Extract and Probiotic Supplementation Alleviate Copper-Induced Nephrotoxicity via Modulating Oxidative Stress, Inflammation, and Apoptosis in Broiler Chickens.

The present study aimed to assess the potential protective effects of cinnamon (Cinnamomum zeylanicum, Cin) and probiotic against CuSO4-induced nephrotoxicity in broiler chickens. One-day-old Cobb chicks were assigned into seven groups (15 birds/group): control group, fed basal diet; Cin group, fed the basal diet mixed with Cin (200 mg/kg); PR group, receiving PR (1 g/4 L water); Cu group, fed the basal diets mixed with CuSO4 (300 mg/kg); Cu + Cin group; Cu + PR group; and Cu + Cin + PR group. All treatments were given daily for 6 weeks. Treatment of Cu-intoxicated chickens with Cin and/or PR reduced (p < 0.05) Cu contents in renal tissues and serum levels of urea, creatinine, and uric acid compared to the Cu group. Moreover, Cin and PR treatment decreased lipid peroxidation and increased antioxidant enzyme activities in chickens' kidney. Additionally, significant reduction (p < 0.05) in the mRNA expression of tumor necrosis factor alpha (TNF-α), interleukin (IL-2) and Bax, and in cyclooxygenase (COX-II) enzyme expression, and significant elevation (p < 0.05) in mRNA expression of IL-10 and Bcl-2 were observed in kidneys of Cu + Cin, Cu + PR, and Cu + Cin + PR groups compared to Cu group. Conclusively, Cin and/or PR afford considerable renal protection against Cu-induced nephrotoxicity in chickens.

Tissue Residues and Pharmacokinetic/Pharmacodynamic Modeling of Tiamulin Against Mycoplasma anatis in Ducks.

The pharmacokinetics of tiamulin were studied in 2 groups of ducks (n = 6) after its oral administration at 2 different doses (30 and 60 mg/kg, respectively). Plasma concentrations of tiamulin were measured by high performance liquid chromatography at different time points up to 24 h post-administration. The maximum plasma concentrations were 0.77 and 2.32 µg/mL attained at 2 h (Tmax) for 30 and 60 mg/kg, respectively. The elimination half-lives for these 2 doses were 3.54 and 6.34 h, respectively. The minimum inhibitory concentration for tiamulin against Mycoplasma anatis (M. anatis) strain 1340 was determined to be 0.06 µg/mL. The proper oral dose of tiamulin against M. anatis in ducks was calculated to be 35 mg/kg/day using the pharmacokinetic/pharmacodynamic modeling. Tiamulin was administered orally (40 mg/kg/day) to 30 ducks for 3 successive days to determine its residues in edible tissues and its preslaughter withdrawal time. The highest tiamulin residues were detected in the liver, followed by the muscle, whereas lower concentrations were detected in the skin and fat. The estimated withdrawal periods of tiamulin were 6, 5, 3, and 3 days for liver, muscle, skin, and fat, respectively. Therefore, an oral dosage regimen of 35 mg/kg/day should be adequate for tiamulin against M. anatis. We recommend a preslaughter withdrawal period of 6 days when ducks are treated with 40 mg tiamulin/kg/day, orally, for 3 days.

Pharmacokinetics, tissue residues, and ex vivo pharmacodynamics of tylosin against Mycoplasma anatis in ducks.

The pharmacokinetics of tylosin were investigated in 3 groups of ducks (n = 6). They received a single dose of tylosin (50 mg/kg) by intravenous (IV), intramuscular (IM), and oral administrations, respectively. Plasma samples were collected at various time points to 24 hr post-administration to evaluate tylosin concentration over time. Additionally, tylosin residues in tissues and its withdrawal time were assessed using 30 ducks which received tylosin orally (50 mg/kg) once daily for 5 consecutive days. After IV administration, the volume of distribution, elimination half-life, area under the plasma concentration-time curve, and the total body clearance were 7.07 ± 1.98 L/kg, 2.04 hr, 19.47 µg hr/ml, and 2.82 L hr-1  kg-1 , respectively. After IM and oral administrations, the maximum plasma concentrations were 3.70 and 2.75 µg/ml achieved at 1 and 2 hr, and the bioavailability was 93.95% and 75.77%, respectively. The calculated withdrawal periods of tylosin were 13, 8, and 5 days for kidney, liver, and muscle, respectively. For the pharmacodynamic profile, the minimum inhibitory concentration for tylosin against M. anatis strain 1,340 was 1 µg/ml. The calculated optimal oral dose of tylosin against M. anatis in ducks based on the ex vivo pharmacokinetic/pharmacodynamic modeling was 61 mg kg-1  day-1 .