Browsing by Author "Corum O."

Now showing 1 - 20 of 49

A cardioprotective role of Nerium oleander with the expression of hypoxia inducible factor 2A mRNA by increasing antioxidant enzymes in rat heart tissue
(2018-01-01) Hitit M.; Corum O.; Corum D.D.; Donmez H.; Cetin G.; Dik B.; Er A.
Background: Nerium oleander (NO) distillate is used to either protect heart cells against oxidative stress or reduce the risk of cardiovascular disease by regulating the production of reactive oxygen species. Hypoxia-inducible factors (HIFs) regulate cellular antioxidant defense mechanisms under hypoxic conditions in which heart cells survive; however, the key responsible mechanism of NO distillate for cardioprotection remains elusive. The objective of this study was to evaluate the effects on heart tissue at different time intervals after administering NO distillate intraperitoneally (IP) while considering the transcriptional regulation of HIFs and representative antioxidant enzymes. Materials, Methods & Results: The NO plant was chopped, and distillated water was added. The mixture was distilled, and the distillate separated and collected into tubes, after which it was lyophilized to obtain dry material. Twenty male Wistar albino rats (2-3 month-old, 250-300 g each) were used in the study. The rats were randomly divided into four groups. The control group (n = 5) received IP injections of saline; the remaining 15 rats received IP injections of a single dose of 7.5 mL NO distillate. The NO distillate injected rats were divided into three groups according to the time from injection to harvest the heart tissue samples. The tissues were collected at 0 h (control; n = 5), 2 h (group 2; n = 5), 4 h (group 3; n = 5), and 8 h (group 4; n = 5) after injection and under general anesthesia (60 mg/kg ketamine, IP + 10 mg/kg xylazine, IP). Quantitative polymerase chain reaction (qPCR) was used to assess the expression profiles of the genes of interest in the heart tissues. Hypoxanthine phosphoribosyltransferase was used as the reference gene. The expression of manganese superoxide dismutase (MnSOD) mRNA was in a steady state level between the control group and group 2 (P > 0.05); however, it significantly increased in group 3 and 4 compared with that in the control (P < 0.05). Expression of catalase (CAT) mRNA was significantly higher in group 2 than in the control group (P < 0.05) although it was lower in group 3 and 4 than in group 2 (P < 0.05); however, it appeared to be similar among the control group, group 3, and group 4 (P > 0.05). Copper (Cu) SOD mRNA was equally expressed in both the control group and group 2 (P > 0.05) but was lower in group 3 and 4 than in group 2 (P < 0.05). Expressions of HIF1A, HIF2A, and HIF3A mRNA were detected in the rat heart tissues in the control and 2, 4, and 8 h after administration of NO distillate. Expression of HIF1A mRNA was in a steady state and did not differ among groups 2, 3, and 4 (P > 0.05). Similarly, the expression of HIF2A mRNA did not change between the control group and group 2 (P > 0.05); however, it was higher in group 3 than in the control (P < 0.05) and tended to be higher in group 3 than in group 2 (P = 0.063). HIF3A mRNA expression did not change significantly in the heart tissue of any of the groups (P > 0.05). Discussion: The present study using rats determined that MnSOD, CAT, CuSOD, HIF1A, HIF2A, and HIF3A mRNA are expressed in the heart tissues after administration of NO distillate. The increased expression of HIF2A mRNA after 4 h in accordance with a rise in CAT mRNA after 2 h, and MnSOD mRNA after 4 and 8 h might confirm the role of HIF2A mRNA in oxidative stress defense by regulating antioxidant enzymes; consequently, this study may expand our understanding of uses of NO distillate with respect to molecular pathways.
A novel herbal immunostimulant for rainbow trout (Oncorhynchus mykiss) against Yersinia ruckeri
(2021-03-01) Terzi E.; Kucukkosker B.; Bilen S.; Kenanoglu O.N.; Corum O.; Özbek M.; Parug S.S.
In this 21-day study, we examined the effects of the aqueous methanolic extract of thin-skinned plum (Prunus domestica) on growth, immune response and resistance to a pathogenic bacterium, Yersinia ruckeri in rainbow trout (Oncorhynchus mykiss). Fish were fed with diets containing thin-skinned plum extract doses as 0 (Control) 0.1 (PD01), 0.5 (PD05) and 1% (PD1) ad libitum twice in a day. At the end of the study, growth was affected positively but not significantly. Feed conversion ratio (FCR) was decreased in the PD01 group (P < 0.05). There were elevated respiratory burst and potential bacterial killing activities on the 7th day in the PD1 fish group. No differences were observed in lysozyme activity (P > 0.05). An increased myeloperoxidase activity was recorded on the 14th day of study. Expression of interleukin and COX-2 genes was elevated on the 7th day of study in the kidney and intestine of treated fish. Histological results indicated no marked changes in organs (gill, kidney, liver and spleen) of PD treated fish groups. Challenge results of fish in all plum extract-treated groups showed an increased survival rate against Y. ruckeri (P < 0.05). This study indicated that the thin-skinned plum aqueous methanolic extract could improve innate immunity, survival against Y. ruckeri and decrease the FCR level.
Alcoholic extract of tarantula cubensis induces apoptosis in MCF-7 cell line
(2017-01-01) Ayse E.R.; Corum O.; Corum D.; Hitit M.; Donmez H.; Guzeloglu A.
Tarantula cubensis Alcoholic Extract (TCAE) is a homeopathic agent used for treating many disorders. This study aimed to define the effects of TCAE on the breast carcinoma cell line (MCF-7). After various concentrations (10, 20, 40, 80 and 160 µl/ml) of TCAE were applied to MCF-7 cells and the human embryonic kidney cell line (HEK293), the cells were incubated for 1, 3, 6, 9, 12, 24 and 48 h, followed by analysis by MTT assays. According to the results of the MTT assays, cells treated with 20 or 40 µl/ml TCAE for 6 h were applied to apoptosis analysis by flow cytometry. Secreted levels of tumor necrosis factor alpha (TNFα), interleukin (IL)-1β, IL-6, IL-10, Interferon-γ (IFNγ), Transforming Growth Factor-β (TGFβ), and Nuclear Factor-kappa B (NF-κB) were measured using ELISAs. TNFα and TGFβ levels increased while IL-6 and IL-10 levels fluctuated in MCF-7 cells. In conclusion, our study suggests that TCAE may change the normal cancer physiology and lead to cell death by activating apoptosis in MCF-7 cells.
Effect of benzylpenicillin on intravenous pharmacokinetics of acyclovir in red-eared slider turtles (Trachemys scripta elegans)
(2020-07-01) D. Corum D.; Corum O.; Atik O.; E. Faki H.; Altan F.; Uney K.
The aim of this study was to determine the effect of benzylpenicillin on the pharmacokinetics of acyclovir in red-eared slider turtles (Trachemys scripta elegans). Six clinically healthy red-eared slider turtles weighing 400 and 580 g were used for the study. Acyclovir (40 mg/kg) and benzylpenicillin (30 mg/kg) were administered intravenously to turtles. In the study, the cross-pharmacokinetic design (2 × 2) with a 30-day washout period was performed in two periods. Plasma concentrations of acyclovir were assayed using the high-performance liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated by two-compartment open pharmacokinetic model. Following the administration of acyclovir alone, elimination half-life (t1/2β), area under the plasma concentration–time curve (AUC), total clearance (ClT), and volume of distribution at steady-state (Vdss) were 20.12 hr, 1,372 hr * µg/mL, 0.03 L hr−1 kg−1, and 0.84 L/kg, respectively. Benzylpenicillin administration increased t1/2β, AUC, and Vdss while decreased ClT of acyclovir. These results showed that benzylpenicillin changed the pharmacokinetics of acyclovir following simultaneous administration in turtles. However, further research is needed to determine molecular mechanism of interaction in turtle.
Effect of castration procedure on the pharmacokinetics of meloxicam in goat kids
(2020-09-01) Tekeli I.O.; Turk E.; Durna Corum D.; Corum O.; Uney K.
The aim of this study was to determine the changes in the pharmacokinetics of meloxicam in goat kids who were castrated following the administration of xylazine. Six goat kids were used for the study. The study was performed in two periods according to a longitudinal study, with a 15-day washout period between periods. In the first period (Control group), 1 mg/kg meloxicam was administered by i.v. route to kids. In the second period (Castration group), the kids were sedated with 0.3 mg/kg xylazine and castration was performed following meloxicam administration. Plasma meloxicam concentration was analyzed using HPLC-UV, and pharmacokinetic parameters were calculated by noncompartmental model. In the control group following the administration of meloxicam, mean elimination half-life (t1/2ʎz), area under the concentration–time curve (AUC0−∞), total body clearance (ClT), and volume of distribution at steady-state (Vdss) were 13.50 ± 0.62 hr, 41.10 ± 2.86 hr µg/ml, 24.43 ± 1.75 ml hr−1 kg−1, and 0.45 ± 0.03 L/kg, respectively. In the castration group, the t1/2ʎz of meloxicam prolonged, AUC0−∞ increased, and ClT and Vdss decreased. In conclusion, the excretion of meloxicam from the body slowed and the t1/2ʎz was prolonged in the castrated goat kids following xylazine administration. However, there is a need to determine the pharmacodynamics of meloxicam in castrated goat kids.
Effect of dose on the intravenous pharmacokinetics of tolfenamic acid in goats
(2020-09-01) Tekeli I.O.; Turk E.; Durna Corum D.; Corum O.; Kirgiz F.C.; Uney K.
The objective of this study was to determine the pharmacokinetics of tolfenamic acid (TA) following intravenous (IV) administration at doses of 2 and 4 mg/kg in goats. In this study, six healthy goats were used. TA was administered intravenously to each goat at 2 and 4 mg/kg doses in a cross-over pharmacokinetic design with a 15-day washout period. Plasma concentrations of TA were analyzed using the high performance liquid chromatography with ultraviolet detector, and pharmacokinetic parameters were assigned by noncompartmental analysis. Following IV administration at dose of 2 mg/kg, area under the concentration–time curve (AUC0−∞), elimination half-life (t1/2ʎz), total clearance (ClT) and volume of distribution at steady state (Vdss) were 6.64 ± 0.81 hr*µg/ml, 1.57 ± 0.14 hr, 0.30 ± 0.04 L h-1 kg-1 and 0.40 ± 0.05 L/kg, respectively. After the administration of TA at a dose of 4 mg/kg showed prolonged t1/2ʎz, increased dose-normalized AUC0-∞, and decreased ClT. In goats, TA at 4 mg/kg dose can be administered wider dose intervals compared to the 2 mg/kg dose. However, further studies are needed to determine the effect of different doses on the clinical efficacy of TA in goats.
Effect of ketoprofen and tolfenamic acid on intravenous pharmacokinetics of ceftriaxone in sheep
(2021-11-01) Cetin G.; Durna Corum D.; Corum O.; Atik O.; Coskun D.; Uney K.
In this study, the pharmacokinetics of ceftriaxone (40 mg/kg) was determined following a single intravenous (IV) administration of ceftriaxone alone and co-administration with ketoprofen (3 mg/kg) or tolfenamic acid (2 mg/kg) in sheep. Eight healthy Akkaraman sheep (2.4 ± 0.3 years and 44 ± 4 kg of body weight) were used. The study was carried out according to the longitudinal design in three periods with a 15-day washout period between administrations. In the first period, sheep received ceftriaxone alone via an IV injection. In the second and third periods, the same sheep received ceftriaxone in combination with ketoprofen and tolfenamic acid, respectively. Plasma concentrations of ceftriaxone were assayed by high-performance liquid chromatography and analyzed using non-compartmental analysis. Following the administration of ceftriaxone alone, the elimination half-life (t1/2ʎz), area under the plasma concentration–time curve from zero (0) hours to infinity (∞) (AUC0-∞), total clearance (ClT), and volume of distribution at steady state were 1.42 h, 182.41 h*µg/ml, 0.22 L/h/kg, and 0.17 L/kg, respectively. While ketoprofen and tolfenamic acid significantly increased the t1/2ʎz and AUC0-∞ of ceftriaxone, they significantly reduced the ClT. Ceftriaxone (40 mg/kg, IV) in concurrent use with ketoprofen and tolfenamic acid can be administrated at the 12 h dosing intervals to maintain T> minimum inhibitory concentration (MIC) values above 60% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 and ≤1 μg/mL, respectively, in sheep with an inflammatory condition.
Effect of ketoprofen co-administration on pharmacokinetics of cefquinome following repeated administration in goats
(2020-09-01) Tekeli I.O.; Turk E.; Durna Corum D.; Corum O.; Kirgiz F.C.; Sakin F.; Uney K.
The pharmacokinetics of cefquinome (2 mg/kg every 24 hr for 5 days) was determined following intramuscular administration alone and co-administration with ketoprofen (3 mg/kg every 24 hr for 5 days) in goats. Six goats were used for the study. In the study, the crossover pharmacokinetics design with 20-day washout period was performed in two periods. Plasma concentrations of cefquinome were assayed using high-performance liquid chromatography by ultraviolet detection. The mean terminal elimination half-life (t1/2ʎz), area under the concentration–time curve (AUC0–24), peak concentration (Cmax), apparent volume of distribution (Vdarea/F), and total body clearance (CL/F) of cefquinome after the administration alone were 4.85 hr, 11.06 hr*µg/ml, 2.37 µg/mL, 1.23 L/kg, and 0.17 L/h/kg after the first dose, and 5.88 hr, 17.01 hr*µg/mL, 3.04 µg/mL, 0.95 L/kg, and 0.11 L/h/kg after the last dose. Ketoprofen significantly prolonged t1/2ʎz of cefquinome, increased AUC0–24 and Cmax, and decreased Vdarea/F and CL/F. Cefquinome exhibited low accumulation after the administration alone and in combination with ketoprofen. These results indicated that ketoprofen prolonged the elimination of cefquinome in goats. The 24-hr dosing intervals at 2 mg/kg dose of cefquinome, which co-administered with ketoprofen, may maintain T> minimum inhibitory concentration (MIC) values above 40% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 μg/ml in goats with an inflammatory condition.
Effect of ketoprofen on intravenous pharmacokinetics of ganciclovir in chukar partridges (Alectoris chukar)
(2022-01-01) Corum O.; Uney K.; Durna Corum D.; Atik O.; Coskun D.; Zhunushova A.; Elmas M.
The aim of the study was to determine the effect of ketoprofen (2 mg/kg) on the intravenous pharmacokinetics of ganciclovir (10 mg/kg) in chukar partridges (Alectoris chukar). Eight clinically healthy partridges were used in the study. The study was performed in two periods using a cross-over design following a 15-day drug washout period. Plasma concentrations of ganciclovir were determined using the high-pressure liquid chromatography-ultraviolet detector and analyzed by non-compartmental analysis. The elimination half-life (t1/2ʎz), area under the concentration-time curve (AUC0-∞), total body clearance, and volume of distribution at steady state of ganciclovir were 1.63 h, 33.22 h*μg/ml, 0.30 L/h/kg, and 0.53 L/kg, respectively. Ketoprofen administration increased the t1/2ʎz and AUC0-∞ of ganciclovir by 78% and 108%, respectively, and while decreased ClT by 53%. The increased plasma concentration and prolonged elimination half-life of ganciclovir caused by ketoprofen may result in the prolonged duration of action and therapeutic effect of ganciclovir. However, the concomitant use requires determination of the pharmacokinetics of ketoprofen and the safety of both drugs.
Effect of supportive therapy on the pharmacokinetics of intravenous marbofloxacin in endotoxemic sheep
(2020-05-01) Coskun D.; Corum O.; Yazar E.
The purpose of this study was to determine the influences of supportive therapy (ST) on the pharmacokinetics (PK) of marbofloxacin in lipopolysaccharide (LPS)-induced endotoxemic sheep. Furthermore, minimum inhibitory concentration (MIC) of marbofloxacin against Escherichia coli, Mannheimia haemolytica, Pasteurella multocida, Klebsiella pneumoniae, Salmonella spp., and Staphylococcus aureus was determined. The study was performed using a three-period cross PK design following a 15-day washout period. In the first period, marbofloxacin (10 mg/kg) was administered by an intravenous (IV) injection. In the second and third periods, marbofloxacin was co-administered with ST (lactated ringer + 5% dextrose + 0.45% sodium chloride, IV, 20 ml/kg, dexamethasone 0.5 mg/kg, SC) and ST + LPS (E. coli O55:B5, 10 µg/kg), respectively. Plasma marbofloxacin concentration was measured using HPLC-UV. Following IV administration of marbofloxacin alone, the (Formula presented.), AUC0–∞, ClT, and Vdss were 2.87 hr, 34.73 hr × µg/ml, 0.29 L hr−1 kg−1, and 0.87 L/kg, respectively. While no change was found in the MBX + ST group in terms of the PK parameters of marbofloxacin, it was determined that the ClT of marbofloxacin decreased, AUC0–∞ increased, and (Formula presented.) and MRT prolonged in the MBX + ST + LPS group. MIC values of marbofloxacin were 0.031 to >16 µg/ml for E. coli, 0.016 to >16 µg/ml for M. haemolytica, 0.016–1 µg/ml for P. multocida, 0.016–0.25 µg/ml for K. pneumoniae, 0.031–0.063 µg/ml for Salmonella spp., and 0.031–1 µg/ml for S. aureus. The study results show the necessity to make a dose adjustment of marbofloxacin following concomitant administration of ST in endotoxemic sheep. Also, the PK and pharmacodynamic effect of marbofloxacin needs to be determined in naturally infected septicemic sheep following concomitant administration of single and ST.
Effects of mulberry extract on the liver pathology and serum biochemical parameters in carmustine administrated rats
(2022-01-01) Ipek V.; Balkan B.M.; Inanc M.E.; Kaplan O.; Corum O.; Gungor S.; Karaca H.; Ata A.
BACKGROUND: Carmustine is a chemotherapeutic agent that is mainly used in the treatment of glioblastoma and can cause toxic effects on various organs, including the liver. The white mulberry extract has anti-Apoptotic and anti-oxidant effects. OBJECTIVE: The study aimed at investigating the effects of the dried white mulberry extract on the pathology, apoptosis, and oxidative stress in the liver, as well as the levels of serum adenosine deaminase, glutathione peroxidase, superoxide dismutase, ceruloplasmin, paraoxonase, and malondialdehyde in carmustine-Administrated rats. METHODS: Forty-Two rats divided into six groups were used in this study. BCNU was administrated intraperitoneally (IP) (5 mg/kg body weight (BW)/week) for 10 weeks to the BCNU and BCNU-DWME groups. DWME was administered (600 mg/kg-BW by oral gavage) daily for 10 weeks to the DWME and BCNU-DWME groups. After the experimental procedure, histopathological, immunohistochemical, and biochemical analyses were performed. RESULTS: Carmustine caused biliary hyperplasia at a dose of 5 mg/kg. However, the mulberry extract was not effective in alleviating this pathology. Furthermore, the administration of carmustine induced apoptosis in hepatocytes, and the mulberry extract had an anti-Apoptotic effect. Carmustine increased the 8-OHdG activity in the liver, and dried mulberry extract ameliorated this activity. Although there was no significant difference in the serum oxidative stress parameters between the groups, carmustine significantly increased the adenosine deaminase activity during the recovery period, while mulberry extracts partially ameliorated these effects in the recovery period. CONCLUSIONS: Dried white mulberry extract has anti-Apoptotic and anti-oxidative effects against carmustine-induced toxicity.
Effects of single and repeated doses on disposition and kinetics of doxycycline hyclate in goats
(2020-06-01) Turk E.; Corum O.; Tekeli I.O.; Sakin F.; Uney K.
The aims of this study in goats were to determine the pharmacokinetics of doxycycline hyclate following single intravenous (IV), intramuscular (IM) and oral administrations of 20 mg/kg and to evaluate the pharmacokinetics and accumulation of doxycycline hyclate after repeated oral administrations at a 20 mg/kg dose every 24 h for 5 days. Six healthy male goats were used for the study. The study was performed in four periods according to a longitudinal study with a 15-day washout period. Plasma concentrations of doxycycline were determined using HPLC-UV and analyzed by a non-compartmental method. IM injection of doxycycline caused swelling and pain due to irritation in the injection site. After IM and oral administrations, terminal elimination half-life (t1/2λz ) and mean residence time (MRT) were prolonged and areas under the curve (AUCs) were low. The mean bioavailability of IM and oral administration was 51.51% and 31.39%, respectively. Following repeated oral administration, the accumulation ratio of doxycycline was 1.76. Pharmacokinetic properties including weak accumulation, wide distribution volume and long elimination half-life can make doxycycline hyclate valuable for repeated use via an oral route in the treatment of some infectious diseases in goats. However, the determination of pharmacodynamic effects on susceptible pathogens isolated from goats is also necessary to confirm the drug dosage regimen.
Effects of Temperature on the Pharmacokinetics, Tissue Residues, and Withdrawal Times of Doxycycline in Rainbow Trout (Oncorhynchus mykiss) following Oral Administration
(2023-06-01) Corum O.; Uney K.; Terzi E.; Durna Corum D.; Coskun D.; Altan F.; Elmas M.
The purpose of this study was to compare the pharmacokinetics, tissue residues, and withdrawal times of doxycycline after oral administration in rainbow trout reared at 10 and 17 °C. Fish received a 20 mg/kg oral dose of doxycycline after a single or 5-day administration. Six rainbow trout were used at each sampling time point for plasma and tissue samples, including liver, kidney, and muscle and skin. The doxycycline concentration in the samples was determined using high-performance liquid chromatography with ultraviolet detector. The pharmacokinetic data were evaluated by non-compartmental kinetic analysis. The WT 1.4 software program was used to estimate the withdrawal times. The increase of temperature from 10 to 17 °C shortened the elimination half-life from 41.72 to 28.87 h, increased the area under the concentration–time curve from 173.23 to 240.96 h * μg/mL, and increased the peak plasma concentration from 3.48 to 5.50 μg/mL. At 10 and 17 °C, the doxycycline concentration was obtained in liver > kidney > plasma > muscle and skin. According to the MRL values stated for muscle and skin in Europe and China (100 μg/kg) and in Japan (50 μg/kg), the withdrawal times of doxycycline at 10 and 17 °C were 35 and 31 days, respectively, for Europe and China and 43 and 35 days, respectively, for Japan. Since temperature significantly affected pharmacokinetic behavior and withdrawal times of doxycycline in rainbow trout, temperature-dependent dosing regimens and withdrawal times of doxycycline might be necessary.
Inﬂuences of tolfenamic acid and ﬂunixin meglumine on the disposition kinetics of levoﬂoxacin in sheep
(2020-03-01) Corum D.D.; Corum O.; Yildiz R.; Faki H.E.; Ider M.; Cetin G.; Uney K.
The pharmacokinetics of levofloxacin (4 mg/kg), administered both alone and in combination with tolfenamic acid (2 mg/kg) and flunixin meglumine (2.2 mg/kg), was established after intravenous administration in sheep. Plasma levofloxacin concentrations were assayed by high-performance liquid chromatography and analysed according to the two-compartment open model. Following the administration of levofloxacin alone, the mean distribution half-life, elimination half-life, total clearance, volume of distribution at steady state and area under the plasma concentration-time curve were 0.20 h, 1.82 h, 0.39 L/h/kg, 0.96 L/kg and 10.40 h 3 mg/mL, respectively. Tolfenamic acid and ﬂunixin meglumine caused a slow elimination and increased plasma concentrations of levoﬂoxacin in combination administration. Levoﬂoxacin, with an alteration in the dosage regimen, can be used effectively with tolfenamic acid and ﬂunixin meglumine for the therapy of infections and inﬂammatory conditions in sheep.
Intravenous pharmacokinetics of moxifloxacin following simultaneous administration with flunixin meglumine or diclofenac in sheep
(2020-03-01) Altan F.; Corum O.; Yildiz R.; Eser Faki H.; Ider M.; Ok M.; Uney K.
In this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co-administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 ± 0.3 years and 53.5 ± 5 kg of body weight) were used. A longitudinal design with a 15-day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co-administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high-performance liquid chromatography. The pharmacokinetic parameters were calculated using a two-compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half-life (t1/2β), total body clearance (ClT), volume of distribution at steady state (Vdss) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h−1 kg−1, 1.66 L/kg and 8.91 hr*µg/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t1/2β and AUC of moxifloxacin, they significantly reduced the ClT and Vdss. These results suggest that anti-inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.
Mucus from different fish species alleviates carrageenan-induced inflammatory paw edema in rats
(2020-10-01) Hitit M.; Corum O.; Ozbek M.; Uney K.; Terzi E.; Arslan G.; Sonmez A.
Objective: To determine the anti-inflammatory effects of mucus obtained from different fish species on the carrageenan-induced acute paw edema in rats. Methods: Forty-two rats were randomly divided into seven groups. Acute paw edema was induced by 0.1 mL of 1% carrageenan, and a single dose of diclofenac and lyophilized mucus (25 mg/kg) of rainbow trout, brook trout, European sea bass, and gilthead sea bream were administered to rats through gastric gavage 1 h before carrageenan treatment. Rat paws were measured before and 1-4 h after carrageenan treatment. The mRNA expressions of cytokines (TNF-α, IL-1β, IL-6, IL-10, and TGF-β), antioxidant markers (catalase and superoxide dismutase), and COX-2 were investigated using quantitative polymerase chain reaction. The histopathological changes were evaluated by hematoxylin and eosin staining. Results: The inhibition percentage of carrageenan-induced paw edema by different fish mucus ranged from 52.46% to 74.86% at 4 h. Histopathological evaluation showed that all fish mucus diminished carrageenan-induced edema and inflammatory cell infiltration. The upregulation of IL-1β mRNA induced by carrageenan was decreased by the mucus of rainbow trout and gilthead sea bream while an increase in the expression of IL-6 mRNA was reduced by the mucus of rainbow trout, brook trout, and gilthead sea bream. In addition, the mRNA expression of superoxide dismutase was higher in the rainbow trout mucus group than the carrageenan group. Conclusions: Mucus obtained from different fish species may have anti-inflammatory effects.
Pentoxifylline may restore kanamycin-induced renal damage in rats
(2018-01-01) Corum O.; Ozdemir O.; Hitit M.; Corum D.D.; Coskun D.; Er A.
Background: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the long term. 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 by using pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objective of 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 normal saline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifylline twice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for 20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injections of 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac puncture under general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediately removed, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogram parameters were measured using a blood cell count apparatus and serum biochemical parameters were measured using an autoanalyzer. Kanamycin also caused (P < 0.05) tubular degeneration and tubular dilatation. Although pentoxifylline significantly reduced the level of kanamycin-induced tubular degeneration (P < 0.05), it did not significantly reduce tubular dilatation. Increases in relative kidney weights (P < 0.05) and in interstitial mononuclear cell (MNC) infiltrates were observed in the kanamycin and kanamycin + pentoxifylline groups compared to those in the control and pentoxifylline groups. Statistically significant changes were determined in the levels of some hemogram and biochemical parameters within reference ranges (P < 0.05). Discussion: In this study, both tubular degeneration and dilatation were observed in the kanamycin group. Pentoxifylline inhibited (P < 0.05) kanamycin-induced tubular degeneration and appeared to also reduce tubular dilatation, although this reduction was not significant. Tubular necrosis, epithelial edema of proximal tubules, tubular fibrosis, and perivascular inflammation might also be observed in aminoglycoside-induced nephrotoxicity. In current research, pentoxifylline prevented tubular damage induced by kanamycin, but did not inhibit infiltration by MNCs. Pentoxifylline also ameliorated amikacin- or gentamycin-induced histopathologic changes, especially those associated with tubular structures. The protective effects of pentoxifylline on kanamycin-induced tubular nephrotoxicity in this research might be a result of its stimulating the production of prostaglandin, a vasodilator, and of its improving microcirculation. Although the anti-inflammatory effects of pentoxifylline have been reported, these did not inhibit kanamycin-induced infiltration by interstitial MNCs in the present study. These results could indicate that the anti-inflammatory effects of pentoxifylline are not obvious and/or are dose dependent. Statistically significantly changes were determined in the levels of some hemogram and biochemical parameters in reference ranges. However, these changes were within the reference ranges for rats. These results suggested that kanamycin-induced tubular degeneration and dilatation might be prevented by administering pentoxifylline.
Pharmacokinetic/pharmacodynamic integration of marbofloxacin after oral and intravenous administration in rainbow trout (Oncorhynchus mykiss)
(2020-01-01) Corum O.; Terzi E.; Durna Corum D.; Kenanoglu O.; Bilen S.; Uney K.
The pharmaco-kinetic/dynamic of marbofloxacin was investigated after single intravenous (IV) and oral administration of 10 mg/kg in 192 healthy rainbow trout at 13 ± 1.2 °C. The plasma concentrations of marbofloxacin were determined by high-performance liquid chromatography-ultraviolet detection. After IV and oral administration, the plasma concentration–time data were described by a noncompartmental analysis. The minimal inhibitory concentration (MIC) of marbofloxacin against Yersinia ruckeri, Aeromonas hydrophila, Pseudomonas fluorescens and P. putida were determined by broth dilution method at 13 °C. After IV administration, the elimination half-life (t1/2ʎz), area under the concentration-versus time curve (AUC0-∞), apparent volume of distribution at steady-state and total body clearance of marbofloxacin were 18.05 h, 354.63 h ∗ μg/mL, 0.65 L/kg and 0.03 L/h/kg, respectively. After oral administration, t1/2ʎz, AUC0-∞, the peak plasma concentration, time of maximum concentration and bioavailability were 27.51 h, 135.29 h ∗ μg/mL, 3.74 μg/mL, 4 h and 38.15%, respectively. The respective MICs of marbofloxacin against Y. ruckeri, A. hydrophila, P. fluorescens and P. putida were determined as 0.02 μg/mL, 2.5 μg/mL, 2.5 μg/mL and 5 μg/mL, respectively. Following IV and oral administration of 10 mg/kg marbofloxacin, AUC/MIC and Cmax/MIC values were above the target levels for Y. ruckeri, while this dose was not sufficient for A. hydrophila and Pseudomonas spp. Because the pharmacokinetics and pharmacodynamics of a drug in fish are significantly affected by temperature, the dosage regimen of marbofloxacin should be modified according to temperature.
Pharmacokinetics and bioavailability of carprofen in rainbow trout (Oncorhynchus mykiss) broodstock
(2021-07-01) Uney K.; Corum D.D.; Terzi E.; Corum O.
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 cefquinome and ceftriaxone in premature calves
(2019-11-01) Corum O.; Yildiz R.; Ider M.; Altan F.; Ok M.; Uney K.
The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high-performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half-life (t1/2λz) 1.85 and 3.31 hr, area under the plasma concentration–time curve (AUC0–∞) 15.74 and 174 hr * μg/ml, volume of distribution at steady-state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr−1 kg−1, respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 μg/ml, time to reach peak concentration 1 and 1.5 hr, t1/2λz 4.74 and 3.62 hr, and AUC0–∞ 22.75 and 147 hr * μg/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12-hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of ≤0.5 and ≤4 μg/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.