Investigation of the Effect of Tarantula cubensis Extract on Acute Phase Response

Background: Tarantula cubensis alcoholic extract is used to accelerate wound healing and to relieve edema in many animal species. In addition, it may be useful for many infectious diseases. Considering to these effects, it is believe that these effects may be on immune system. Cytokines (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma) secreted by immune cells and acute phase proteins (haptoglobin, alpha 1 acid glycoprotein, serum amyloid A) secreted by liver play role in acute phase response. The aim of the present study was to determine the effect of Tarantula cubensis alcoholic extract on cytokine and acute phase protein levels in sheep.Materials, Methods & Results: Tarantula cubensis alcoholic extract (6 mL/sheep, subcutaneously, single dose) was administered to 6 healthy sheep. Blood samples were obtained before (0 h) and after treatments at 2, 4, 8, 12, 24 and 48 h. Then, blood samples were centrifuged to obtain serum samples. Acute phase cytokines such as serum tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma and acute phase proteins such as haptoglobin, alpha 1 acid glycoprotein and serum amyloid-A concentrations were determined with commercially available kits on ELISA reader. Administration of Tarantula cubensis alcoholic extract caused fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma levels in sheep. In addition, levels of haptoglobin, alpha 1 acid glycoprotein, serum amyloid A showed fluctuations. But, these fluctuations in acute phase cytokines and acute phase proteins were not statistically significant (P > 0.05).Discussion: Tarantula cubensis alcoholic extract, homeopathic medicine, is used trauma, retentio secundinarium, tendinitis, bluetongue, foot and mouth, metritis and arthritis in many animal species including sheep. Cytokines, secreted against various stimulus including infectious diseases, play role in wound healing and in the regulation of the immune system. In current study, administration of Tarantula cubensis alcoholic extract lead to fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma levels, but these changes were not statistically significant (P > 0.05). Non-statistical fluctuations in cytokines result from inadequate immunological response of sheep against to Tarantula cubensis alcoholic extract. Also, use of molecular analysis techniques may be changed these results. Acute phase proteins are significantly secreted from the liver during the acute phase response. In current study, administration of Tarantula cubensis alcoholic extract in sheep caused non-statistifical fluctuations on haptoglobin, alpha 1 acid glycoprotein and serum amyloid A levels (P > 0.05). Tumor necrosis factor alpha and interleukin-1 beta stimulate synthesis of interleukin-6. Interleukin-6 provides synthesis of acute phase proteins in liver. Non-statistical fluctuations in acute phase proteins result from inadequate stimulus of IL-6. In conclusion, it may be stated that administration of Tarantula cubensis alcoholic extract has no distinctive effect on the acute phase response. However, when Tarantula cubensis alcoholic extract is administered repeated times or other acute phase parameters are evaluated, different results may be observed

Pentoxifylline May Restore Kanamycin-Induced Renal Damage in Rats

Background: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the longterm. The use of one such group of drugs, aminoglycosides, which act as Gram-negative antibacterial therapeutic agents,can lead to nephrotoxicity. It has been hypothesized that aminoglycoside-induced nephrotoxicity might be prevented byusing pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objectiveof this present research was to determine the protective effects of pentoxifylline on kanamycin-induced kidney damage.Materials, Methods & Results: Thirty-two male Wistar rats were divided into four groups as follows: control, pentoxifylline,kanamycin, and kanamycin + pentoxifylline. The control group received intraperitoneal (IP) injections of 0.5 mL normalsaline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifyllinetwice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injectionsof 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac punctureunder general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediatelyremoved, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogramparameters were measured using a blood cell count apparatus and serum biochemical parameters were measured usingan autoanalyzer. Kanamycin also caused (P < 0.05) tubular degeneration and tubular dilatation. Although pentoxifyllinesignificantly reduced the level of kanamycin-induced tubular degeneration (P < 0.05), it did not significantly reduce tubulardilatation. Increases in relative kidney weights (P < 0.05) and in interstitial mononuclear cell (MNC) infiltrates wereobserved in the kanamycin and kanamycin + pentoxifylline groups compared to those in the control and pentoxifyllinegroups. Statistically significant changes were determined in the levels of some hemogram and biochemical parameterswithin reference ranges (P < 0.05).Discussion: In this study, both tubular degeneration and dilatation were observed in the kanamycin group. Pentoxifyllineinhibited (P < 0.05) kanamycin-induced tubular degeneration and appeared to also reduce tubular dilatation, although thisreduction was not significant. Tubular necrosis, epithelial edema of proximal tubules, tubular fibrosis, and perivascularinflammation might also be observed in aminoglycoside-induced nephrotoxicity. In current research, pentoxifylline preventedtubular damage induced by kanamycin, but did not inhibit infiltration by MNCs. Pentoxifylline also amelioratedamikacin- or gentamycin-induced histopathologic changes, especially those associated with tubular structures. The protectiveeffects of pentoxifylline on kanamycin-induced tubular nephrotoxicity in this research might be a result of its stimulatingthe production of prostaglandin, a vasodilator, and of its improving microcirculation. Although the anti-inflammatoryeffects of pentoxifylline have been reported, these did not inhibit kanamycin-induced infiltration by interstitial MNCs inthe present study. These results could indicate that the anti-inflammatory effects of pentoxifylline are not obvious and/orare dose dependent. Statistically significantly changes were determined in the levels of some hemogram and biochemicalparameters in reference ranges. However, these changes were within the reference ranges for rats. These results suggestedthat kanamycin-induced tubular degeneration and dilatation might be prevented by administering pentoxifylline

Changes in novel gastrointestinal and renal injury markers in the blood plasma of sheep following increasing intravenous doses of tolfenamic acid

The administration of high doses of non-steroidal anti-inflammatory drugs (NSAID), such as tolfenamic acid (TA), has undesirable effects on different organs. Some novel biomarkers have been reported that can determine the gastrointestinal and renal injury caused by a high dose of NSAIDs or other toxic substances. This study was aimed at determining the changes in gastrointestinal (TFF2 and HYP), renal (NGAL and KIM-1) and cardiac (cTn-I, CK-MB) injury markers after the use of increasing intravenous doses of TA in sheep. TA was administered intravenously to groups of six sheep each, at the dose levels of 0 (Group 0, i.e., G0), 2 (G2), 4 (G4), 8 (G8) and 16 (G16) mg/kg. The concentrations of the studied biomarkers were measured at 3, 9, 18 and 36 h after administration of TA. The TFF2 and NGAL concentrations in G16 were found to be significantly higher (P < 0.05) than in the other groups except for G8 at different sampling times. HYP concentration in G16 was observed to be significantly (P < 0.05) lower than that in all other groups at 36 h. KIM-1 level in G16 was significantly (P < 0.05) higher than in all other groups at different sampling times. An increase in the renal markers, KIM-1 and NGAL, in G8 was observed before any change in plasma creatinine and urea. The cardiac marker cTn-I in G16 was significantly (P < 0.05) higher than in other groups at different sampling times. The results showed that the novel biomarkers (HYP, TFF2, NGAL, and KIM-1) can be used to determine gastric and renal injury in sheep

Effect of body size on plasma and tissue pharmacokinetics of danofloxacin in rainbow trout (Oncorhynchus mykiss)

© 2024, by the authors. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in Animals. To access the final edited and published work see https://doi.org/10.3390/ani14223302 https://www.mdpi.com/journal/Danofloxacin is a fluoroquinolone antibiotic approved for use in fish. It can be used for bacterial infections in fish of all body sizes. However, physiological differences in fish depending on size may change the pharmacokinetics of danofloxacin and therefore its therapeutic efficacy. In this study, the change in the pharmacokinetics of danofloxacin in rainbow trout of various body sizes was revealed for the first time. The objective of this investigation was to compare the plasma and tissue pharmacokinetics of danofloxacin in rainbow trout of different body sizes. The study was conducted at 14 ± 0.5 ◦C in fish of small, medium, and large body size and danofloxacin was administered orally at a dose of 10 mg/kg. Concentrations of this antimicrobial in tissues and plasma were quantified by high performance liquid chromatography with ultraviolet detector. The plasma elimination half-life (t1/2Lz), volume of distribution (Vdarea/F), total clearance (CL/F), peak concentration (Cmax), and area under the plasma concentration–time curve (AUC0–last) were 27.42 h, 4.65 L/kg, 0.12 L/h/kg, 2.53 μg/mL, and 82.46 h·μg/mL, respectively. Plasma t1/2Lz, AUC0–last and Cmax increased concomitantly with trout growth, whereas CL/F and Vdarea/F decreased. Concentrations in liver, kidney, and muscle tissues were higher than in plasma. Cmax and AUC0–last were significantly higher in large sizes compared to small and medium sizes in all tissues. The scaling factor in small, medium, and large fish was 1.0 for bacteria with MIC thresholds of 0.57, 0.79, and 1.01 μg/mL, respectively. These results show that therapeutic efficacy increases with body size. However, since increases in danofloxacin concentration in tissues of large fish may affect withdrawal time, attention should be paid to the risk of tissue residue

Effect of single dose dexamethasone (0.1 mg/kg) on white blood cell counts and serum glucose levels in healthy ewes

Aim: Aim of this research was to determine that effect of single dose dexamethasone (0.1 mg/kg, SC) on the white blood cell counts and serum glucose levels in healthy ewes. In addition, effects of dexamethasone on the other hemogram and serum biochemical values were evaluated. Materials and Methods: Totally healthy 8 Akkaraman sheep were received with 0.1 mg/kg (SC, single dose) dexamethasone. Blood samples were taken before (0. hour, control) and after treatments at 4, 8, 12, 24, 36, 48 and 72 hours. White blood cell, red blood cell, platelet, hematocrit and hemoglobin levels were measured by hemocell counter, whereas serum glucose, lactate dehydrogenase, alkaline phosphatase, total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin, blood urea nitrogen, creatinine, cholesterol, triglyceride, high density lipoprotein and low density lipoprotein levels were determined by auto-analyzer. Results: Dexamethasone increased (P<0.05) white blood cell and glucose levels when compared to Control (0 hour), and higher levels of these values were monitored during 48 hours. In addition, statistically significance changes were determined in the total bilirubin, triglyceride and blood urea nitrogen concentrations, but these results were within reference range. Conclusion: It may be stated that dexamethasone increases white blood cell count and glucose levels in sheep and its effect may be determined during 2-3 days after treatments

Pharmacokinetics and Bioavailability of Carprofen in Rainbow Trout (Oncorhynchus mykiss) Broodstock

The aim of this study was to determine the pharmacokinetics of carprofen following intravenous (IV), intramuscular (IM) and oral routes to rainbow trout (Oncorhynchus mykiss) broodstock at temperatures of 10 ± 1.5 °C. In this study, thirty-six healthy rainbow trout broodstock (body weight, 1.45 ± 0.30 kg) were used. The plasma concentrations of carprofen were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using non-compartmental analysis. Carprofen was measured up to 192 h for IV route and 240 h for IM, and oral routes in plasma. The elimination half-life (t1/2λz) was 30.66, 46.11, and 41.08 h for IV, IM and oral routes, respectively. Carprofen for the IV route showed the total clearance of 0.02 L/h/kg and volume of distribution at steady state of 0.60 L/kg. For IM and oral routes, the peak plasma concentration (Cmax) was 3.96 and 2.52 μg/mL with the time to reach Cmax of 2 and 4 h, respectively. The bioavailability was 121.89% for IM route and 78.66% for oral route. The favorable pharmacokinetic properties such as the good bioavailability and long t1/2λz for IM and oral route of carprofen suggest the possibility of its effective use for the treatment of various conditions in broodstock

Pharmacokinetics and Bioavailability of Carprofen in Rainbow Trout (Oncorhynchus mykiss) Broodstock

The aim of this study was to determine the pharmacokinetics of carprofen following intravenous (IV), intramuscular (IM) and oral routes to rainbow trout (Oncorhynchus mykiss) broodstock at temperatures of 10 ± 1.5 °C. In this study, thirty-six healthy rainbow trout broodstock (body weight, 1.45 ± 0.30 kg) were used. The plasma concentrations of carprofen were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using non-compartmental analysis. Carprofen was measured up to 192 h for IV route and 240 h for IM, and oral routes in plasma. The elimination half-life (t1/2λz) was 30.66, 46.11, and 41.08 h for IV, IM and oral routes, respectively. Carprofen for the IV route showed the total clearance of 0.02 L/h/kg and volume of distribution at steady state of 0.60 L/kg. For IM and oral routes, the peak plasma concentration (Cmax) was 3.96 and 2.52 μg/mL with the time to reach Cmax of 2 and 4 h, respectively. The bioavailability was 121.89% for IM route and 78.66% for oral route. The favorable pharmacokinetic properties such as the good bioavailability and long t1/2λz for IM and oral route of carprofen suggest the possibility of its effective use for the treatment of various conditions in broodstock.</jats:p

Pharmacokinetics, Tissue Residues, and Withdrawal Times of Oxytetracycline in Rainbow Trout (Oncorhynchus mykiss) after Single- and Multiple-Dose Oral Administration

The aim of this study was to compare the pharmacokinetics of oxytetracycline (OTC) following single- (60 mg/kg) and multiple-dose oral administrations (60 mg/kg, every 24 h for 7 days) in rainbow trout. It also aimed to determine bioavailability after a single dose and tissue residues and withdrawal times after multiple doses. This study was carried out on 420 rainbow trout at 9 &plusmn; 0.8 &deg;C. This study was carried out in two stages: single-dose (intravascular and oral) and multiple-dose treatment. The OTC concentrations in plasma and tissues were measured by high-performance liquid chromatography and analyzed by a non-compartmental method. The withdrawal time (WT) was estimated using the WT 1.4 software. OTC exhibited a long terminal elimination half-life (t1/2&#654;z) after IV and oral administration. The oral bioavailability of OTC was very low (2.80%). In multiple-dose treatment, t1/2&#654;z, the area under the plasma concentration&ndash;time curve and peak plasma concentration increased significantly after the last day compared to the first day. OTC showed strong accumulation after multiple doses with a value of 5.33. OTC concentrations were obtained in the order liver &gt; kidney &gt; muscle+skin &gt; plasma. At 9 &plusmn; 0.8 &deg;C, the WT calculated for muscle+skin was 56 days for Europe and 50 days for China, respectively. The t1/2&#654;z (68.94 h) and time (68 h) above the 1 &micro;g/mL MIC following a single OTC dose may support the extension of the 24 h dosing interval following multiple dosing. However, further studies are required to determine the optimal dosage regimen in multiple-dose OTC treatment in the treatment of infections caused by susceptible pathogens

Influence of Dexamethasone on the Plasma and Milk Disposition Kinetics of Danofloxacin in Lactating Sheep

This study planned to evaluate the impact of low (0.1 mg/kg) and high (1 mg/kg) doses of dexamethasone on the plasma and milk distribution of danofloxacin (6 mg/kg) in sheep after intravenous administration. Utilizing a crossover pharmacokinetic design, the research was conducted on six lactating ewes, with blood and milk samples collected at 18 predetermined time points over a 48-h period. Danofloxacin analysis from plasma and milk samples was performed by high-performance liquid chromatography. The pharmacokinetic data were derived using non-compartmental analysis. Plasma t1/2&#654;z, AUC0&ndash;&infin;, ClT, and Vdss values of danofloxacin were found to be 5.20 h, 9.26 h*&micro;g/mL, 0.65 L/h/kg, and 4.23 L/kg, respectively. The administration of both low and high doses of dexamethasone did not result in any changes in the plasma pharmacokinetics of danofloxacin. Milk t1/2&#654;z, AUC0&ndash;&infin;, and Cmax values of danofloxacin were 4.30 h, 99.52 h*&micro;g/mL, and 20.61 &micro;g/mL, respectively. Dexamethasone administration resulted in prolonged milk t1/2&#654;z, with high-dose dexamethasone significantly enhancing both the milk AUC0&ndash;&infin; and Cmax of danofloxacin. The AUC0&ndash;&infin; milk/AUC0&ndash;&infin; plasma ratio of danofloxacin was 10.75 and was further increased with dexamethasone treatment. These results highlight the necessity for careful evaluation of drug interactions in lactating sheep to ensure both efficacy and safety, as well as the need for further research to establish guidelines for concurrent administration of dexamethasone and danofloxacin