Safety of Antitheilerial Drug Buparvaquone in Rams

Background: Theileriosis is a tick-borne disease caused by Theileria strains of the protozoan species. Buparvaquone is the mostly preferred drug in the treatment theileriosis, while it is safety in sheep, has not been detailed investigated. It has been hypothesized that buparvaquone may show side effects and these effects may be defined some parameters measured from blood in sheep when it is used at the recommended dose and duration. The aim of this research was to determine the effect of buparvaquone on the blood oxidative status, cardiac, hepatic and renal damage and bone marrow function markers.Materials, Methods & Results: In this study, ten adult (> 2 years) Akkaraman rams were used. Healthy rams were placed in paddocks, provided water ad libitum, and fed with appropriate rations during the experiment. Buparvaquone was administered at the dose of 2.5 mg/kg (IM) intramuscularly twice at 3-day intervals. Blood samples were obtained before (0. h, Control) and after drug administration at 0.25, 0.5, 1, 2, 3, 4 and 5 days. The blood samples were transferred to gel tubes, and the sera were removed (2000 g, 15 min). During the study, the heart rate, respiratory rate, and body temperature were measured at each sampling time. In addition, the animals were clinically observed. Plasma oxidative status markers (Malondialdehyde, total antioxidant status, catalase, glutathione peroxidase, superoxide dismutase), serum cardiac (Troponin I, creatine kinase-MBmass, lactate dehydrogenase), hepatic (Alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin, globulin) and renal (Creatinine, blood urea nitrogen) damage markers and hemogram values (white blood cell, red blood cell, platelet, hemogram, hematocrit) were measured. Buparvaquone caused statistically significantly (P 0.05), it was determined that buparvaquone gradually increased the levels of the main oxidative stress marker, MDA, by approximately 2.8 fold. CAT and GPX levels were also found to have decreased by 2.2 fold. Buparvaquone may cause lipid peroxidation by producing free radicals. Some other antiprotozoal drugs may affect the oxidative status and may increase MDA level and decrease SOD level. In this study, MDA, which is an indicator of lipid peroxidation in vivo, was used to partially detect developing lipid peroxidation. Changes in the levels of reduced GPX and CAT enzymes could be attributed to their use in mediating the hydrogen peroxide detoxification mechanisms. The absence of significant changes in the TAS levels in this study suggests that buparvaquone may partially induce oxidative stress by producing hydrogen peroxide, but no significant changes occurred in the oxidative stress level because of the high antioxidant capacity of sheep. In this study, buparvaquone caused a statistically significant increase (P 0.05) significant increase in CK-MBmass. Tn-I and CK-MB levels, which are used to define heart damage in humans, have been successfully used to determine heart damage in sheep. In this research study, the statistically significant increases in Tn-I but not CK-MBmass levels could be considered indicative of mild cardiac damage

utjecaj ambroksola na protuupalni učinak azitromicina u plućnom tkivu

The aim of this study was to compare the effects of two different doses of ambroxol (AMB) co-administered with azithromycin (AZIT) on the concentrations of bronchoalveolar lavage fluid (BALF) cytokines and serum biochemical parameters in an lipopolysaccharide (LPS)-induced acute lung injury mouse model. A total of 78 male Swiss albino mice were used for this investigation. After six mice had been separated as the control group (0 hours), the remaining animals were divided into the following three equal groups: LPS, LPS+AZIT+AMB30 and LPS+AZIT+AMB70. LPS, AZIT and AMB were administered intraperitoneally. BALF and serum samples were collected before (0 hour) and after applications at 4, 8, 16 and 24 hours under general anaesthesia, and then all mice were euthanised by cervical dislocation. Concentrations of tumor necrosis factor (TNF)α, interleukin (IL)-6 and IL-10 in BALF and aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine concentrations in serum were determined. Elevated TNFα and IL-6 concentrations in the LPS group were prevented at 8 and 16 hours in LPS+AZIT+AMB30 group. In addition, both treatment groups inhibited elevated IL-6 concentrations in the LPS group at 16 hours. LPS+AZIT+AMB30 and LPS+AZIT+AMB70 increased IL-10 concentrations at 16 and 4 hours, respectively. LPS caused significant elevations in urea concentrations at all sampling times and statistical fluctuations in other parameters at different sampling times. The increased ALP concentration in LPS group decreased in the treatment groups at 8 hours. In conclusion, the combination of low-dose AMB and AZIT may achieve beneficial effects in pulmonary infections by influencing the cytokine network.Cilj ovog istraživanja bio je usporediti učinke dviju različitih doza ambroksola (AMB), primijenje-nih u kombinaciji s azitromicinom (AZIT), na koncentraciju citokina u bronhoalveolarnoj tekućini (BALF), odnosno na serumske biokemijske pokazatelje u slučaju akutne ozljede pluća izazvane lipopolisaharidom (LPS). Od ukupno 78 miševa, mužjaka Swiss albino soja, 6 je miševa stavljeno u kontrolnu skupinu (0 sati). Ostale životinje su podijeljene u tri jednake skupine: skupinu kojoj je dan LPS, skupinu kojoj je primijenjen LPS + AZIT + AMB30 i skupinu LPS + AZIT + AMB70. LPS, AZIT i AMB primijenjeni su intraperitonealno. BALF i uzorci seruma prikupljeni su prije aplikacije lijekova (0 sati) te 4, 8, 16 i 24 sata poslije aplikacije pod općom anestezijom, nakon čega su svi miševi eutanazirani cervikalnom dislokacijom. Određena je koncentracija tumorskog faktora nekroze alfa (TNF-α), interleukina IL-6 i IL- 10 u BALF-u te koncentracija aspartat-aminotransferaze (AST), alkalne fosfataze (ALP), uree i kreatinina u serumu. Povećanje koncen-tracije TNF-α i IL-6 u skupini kojoj je dan LPS prevenirano je u razdoblju od 8 sati, odnosno 16 sati nakon aplikacije u skupini LPS + AZIT + AMB30. Osim toga, u obje je skupine preveniran porast koncentracije IL-6 nakon 16 sati. Kombinacija LPS + AZIT + AMB30 povećala je koncen-traciju IL-10 u periodu nakon 16 sati, a kombinacija LPS + AZIT + AMB70 nakon 4 sata. LPS je uzrokovao znakovit porast koncentracije uree u svim vremenima uzorkovanja i statističku fluktua-ciju drugih pokazatelja u različitim vremenima uzorkovanja. Povećana koncentracija ALP-a u skupini LPS smanjena je u pokusnim skupinama nakon 8 sati. Zaključeno je da kombinacija male do-ze AMB-a i AZIT-a može blagotvorno djelovati na plućne infekcije putem utjecaja na mrežu citokina

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

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

Protective Effect of <i>Nerium oleander</i> Distillate and <i>Tarantula cubensis</i> Alcoholic Extract on Cancer Biomarkers in Colon and Liver Tissues of Rats with Experimental Colon Cancer

Background: Colon cancers are among the top three causes of cancer-related deaths. This study is a continuation of previous research aiming to identify effective treatments. Objective: This study investigated the effects of Tarantula cubensis alcoholic extract (TCAE) and Nerium oleander (NO) distillate on the levels of midkine, transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), alpha-fetoprotein (AFP), cyclooxygenase (COX)-2, insulin-like growth factor (IGF) and caspase-3 in the liver and colon tissues of rats with experimentally induced colon cancer. Method: The liver and colon tissues of rats were homogeneously divided into control, colon cancer (azoxymethane, AZM), AZM + TCAE, and AZM + NO distillate groups. The levels of midkine, TGF-β, VEGF, AFP, COX-2, IGF, and caspase-3 in the colon and liver tissues were measured by ELISA. Results: The levels of all parameters in colon and liver tissues in the AZM group were higher (p&lt;0.05) than those in the control group. TCAE and NO distillate prevented (p &lt; 0.05) increases in midkine, TGF-β, VEGF, AFP, COX-2, IGF, and caspase-3 levels in the colon. NO distillate prevented the increase in all parameters except IGF, whereas TCAE prevented the increase in all values apart from COX-2 and IGF levels in the liver (p&lt;0.05). Conclusion: NO distillate and TCAE may prevent the studied markers from reaching specified levels observed in the colon in AZM-induced colon cancer. The increases in the levels of the parameters in the liver were not as severe as those in the colon; however, an 18-week study period may not be sufficient for liver metastasis formation. Future molecular studies should investigate the mechanisms and pathways of these treatments in greater detail. </jats:sec

Doxycycline and meloxicam can treat neuroinflammation by increasing activity of antioxidant enzymes in rat brain

The aim of this study is to determine the effects of alone or combined usage of doxycycline and meloxicam on brain superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and matrix metalloproteinase (MMP)-9 levels of lipopolysaccharide (LPS)-induced brain inflammation. Totally 78 rats were divided into 5 groups; Healthy control (n=6), LPS (n=18, 0.05 mu g/mu L/rat, intracranially), LPS+D (n=18, LPS 0.05 mu g/mu L/rat, intracranially and doxycycline 40 mg/kg, intraperitoneally), LPS+M (n=18, LPS 0.05 mu g/mu L/rat, intracranially and meloxicam 2 mg/kg, intraperitoneally), LPS+Combination (n=18, LPS 0.05 mu g/mu L/rat, intracranially and simultaneously both drug combination) groups. Animals were euthanized at 1, 3 and 6 hours following injections and the brains were removed. Brain SOD, CAT, MDA and MMP-9 levels were determined by ELISA reader. Parameters of LPS groups generally different from Healthy control group. When compared to LPS group, increased SOD level of LPS+D at 3 hours and CAT levels of LPS+M and LPS+D groups were determined (P<0.05) at 3 and 6 hours, respectively. In addition, all treatments statistically significantly (P<0.05) decreased MMP-9 levels at 6 hours. In conclusion, doxycycline and meloxicam may show antioxidant effect via increasing antioxidant enzyme production in the brain; however combined usage of drugs may show more beneficial effect for neuroinflammation

Safety of Antitheilerial Drug Buparvaquone in Rams

Background: Theileriosis is a tick-borne disease caused by Theileria strains of the protozoan species. Buparvaquone is the mostly preferred drug in the treatment theileriosis, while it is safety in sheep, has not been detailed investigated. It has been hypothesized that buparvaquone may show side effects and these effects may be defined some parameters measured from blood in sheep when it is used at the recommended dose and duration. The aim of this research was to determine the effect of buparvaquone on the blood oxidative status, cardiac, hepatic and renal damage and bone marrow function markers.Materials, Methods &amp; Results: In this study, ten adult (&gt; 2 years) Akkaraman rams were used. Healthy rams were placed in paddocks, provided water ad libitum, and fed with appropriate rations during the experiment. Buparvaquone was administered at the dose of 2.5 mg/kg (IM) intramuscularly twice at 3-day intervals. Blood samples were obtained before (0. h, Control) and after drug administration at 0.25, 0.5, 1, 2, 3, 4 and 5 days. The blood samples were transferred to gel tubes, and the sera were removed (2000 g, 15 min). During the study, the heart rate, respiratory rate, and body temperature were measured at each sampling time. In addition, the animals were clinically observed. Plasma oxidative status markers (Malondialdehyde, total antioxidant status, catalase, glutathione peroxidase, superoxide dismutase), serum cardiac (Troponin I, creatine kinase-MBmass, lactate dehydrogenase), hepatic (Alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin, globulin) and renal (Creatinine, blood urea nitrogen) damage markers and hemogram values (white blood cell, red blood cell, platelet, hemogram, hematocrit) were measured. Buparvaquone caused statistically significantly (P &lt; 0.05) increases in the troponin I and blood urea nitrogen levels and fluctuations in alkaline phosphatase activity, but there was no any statistically significance difference determined in the other parameters.Discussion: In this study, buparvaquone was administered two times at a dose of 2.5 mg/kg (IM) at 3-day intervals. Although the result was not statistically significant (P &gt; 0.05), it was determined that buparvaquone gradually increased the levels of the main oxidative stress marker, MDA, by approximately 2.8 fold. CAT and GPX levels were also found to have decreased by 2.2 fold. Buparvaquone may cause lipid peroxidation by producing free radicals. Some other antiprotozoal drugs may affect the oxidative status and may increase MDA level and decrease SOD level. In this study, MDA, which is an indicator of lipid peroxidation in vivo, was used to partially detect developing lipid peroxidation. Changes in the levels of reduced GPX and CAT enzymes could be attributed to their use in mediating the hydrogen peroxide detoxification mechanisms. The absence of significant changes in the TAS levels in this study suggests that buparvaquone may partially induce oxidative stress by producing hydrogen peroxide, but no significant changes occurred in the oxidative stress level because of the high antioxidant capacity of sheep. In this study, buparvaquone caused a statistically significant increase (P &lt; 0.05) in the level of Tn-I, which is a marker of specific cardiac damage (P &lt; 0.05), whereas there was no statistically (P &gt; 0.05) significant increase in CK-MBmass. Tn-I and CK-MB levels, which are used to define heart damage in humans, have been successfully used to determine heart damage in sheep. In this research study, the statistically significant increases in Tn-I but not CK-MBmass levels could be considered indicative of mild cardiac damage.</jats:p

Safety of Antitheilerial Drug Buparvaquone in Rams

Background: Theileriosis is a tick-borne disease caused by Theileria strains of the protozoan species. Buparvaquone is the mostly preferred drug in the treatment theileriosis, while it is safety in sheep, has not been detailed investigated. It has been hypothesized that buparvaquone may show side effects and these effects may be defined some parameters measured from blood in sheep when it is used at the recommended dose and duration. The aim of this research was to determine the effect of buparvaquone on the blood oxidative status, cardiac, hepatic and renal damage and bone marrow function markers. Materials, Methods & Results: In this study, ten adult (> 2 years) Akkaraman rams were used. Healthy rams were placed in paddocks, provided water ad libitum, and fed with appropriate rations during the experiment. Buparvaquone was administered at the dose of 2.5 mg/kg (IM) intramuscularly twice at 3-day intervals. Blood samples were obtained before (0. h, Control) and after drug administration at 0.25, 0.5, 1, 2, 3, 4 and 5 days. The blood samples were transferred to gel tubes, and the sera were removed (2000 g, 15 min). During the study, the heart rate, respiratory rate, and body temperature were measured at each sampling time. In addition, the animals were clinically observed. Plasma oxidative status markers (Malondialdehyde, total antioxidant status, catalase, glutathione peroxidase, superoxide dismutase), serum cardiac (Troponin I, creatine kinase-MBmass, lactate dehydrogenase), hepatic (Alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total protein, albumin, globulin) and renal (Creatinine, blood urea nitrogen) damage markers and hemogram values (white blood cell, red blood cell, platelet, hemogram, hematocrit) were measured. Buparvaquone caused statistically significantly (P 0.05), it was determined that buparvaquone gradually increased the levels of the main oxidative stress marker, MDA, by approximately 2.8 fold. CAT and GPX levels were also found to have decreased by 2.2 fold. Buparvaquone may cause lipid peroxidation by producing free radicals. Some other antiprotozoal drugs may affect the oxidative status and may increase MDA level and decrease SOD level. In this study, MDA, which is an indicator of lipid peroxidation in vivo, was used to partially detect developing lipid peroxidation. Changes in the levels of reduced GPX and CAT enzymes could be attributed to their use in mediating the hydrogen peroxide detoxification mechanisms. The absence of significant changes in the TAS levels in this study suggests that buparvaquone may partially induce oxidative stress by producing hydrogen peroxide, but no significant changes occurred in the oxidative stress level because of the high antioxidant capacity of sheep. In this study, buparvaquone caused a statistically significant increase (P 0.05) significant increase in CK-MBmass. Tn-I and CK-MB levels, which are used to define heart damage in humans, have been successfully used to determine heart damage in sheep. In this research study, the statistically significant increases in Tn-I but not CK-MBmass levels could be considered indicative of mild cardiac damage.SUBAPSelcuk University [17401094]This study was supported by SUBAP (No. 17401094)

Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep

ABSTRACT Objective This study aimed to investigate the plasma and milk pharmacokinetics, as well as the withdrawal time (WT) from milk of tolfenamic acid (2 and 4 mg/kg) following intravenous (IV) administration to eight healthy lactating Akkaraman sheep. Methods The trial was conducted in two periods in accordance with a crossover pharmacokinetic design. The concentrations of tolfenamic acid in the plasma and milk were determined using high‐pressure liquid chromatography and evaluated using non‐compartmental analysis. The WT of tolfenamic acid in milk was calculated using the WT 1.4 software. Results Compared to the 2 mg/kg dose, plasma volume of distribution at steady state (from 0.43 to 0.50 L/kg), terminal elimination half‐life (from 2.41 to 4.14 h) and dose‐normalized area under the plasma concentration–time curve (AUC0−∞, from 9.46 to 30.11 h µg/mL) increased, whereas total body clearance (from 0.21 to 0.13 L/h/kg) decreased at the 4 mg/kg dose. The peak milk concentration (Cmax) and AUC0−∞ values in milk were 0.26 µg/mL and 0.28 h µg/mL, respectively, for 2 mg/kg, and 0.43 µg/mL and 0.55 h µg/mL, respectively, for 4 mg/kg. Although the dose‐normalized Cmax of milk decreased depending on the dose, no difference was observed in dose‐normalized AUC0−∞. The AUC0−∞ milk/AUC0−∞ plasma ratio was 0.03 for 2 mg/kg and 0.02 for 4 mg/kg. The WT values calculated for milk at dosages of 2 and 4 mg/kg were 3 and 4 h, respectively. Conclusions A decrease in plasma elimination and an increase in plasma concentration of tolfenamic acid were observed depending on the dose. Tolfenamic acid lowly passed into sheep's milk at 2 and 4 mg/kg doses. This study may provide valuable information for clinicians’ decision‐making processes