In vivo exposure of Albendazole sulphoxide by Haemonchus contortus and correlation between plasma and target tissue or gastrointestinal content dispositions in goats.

Sheep and goats are sharing different helminth parasites including Haemonchus contortus. Control of these helminths is based mainly on the use of anthelmintics. However, in goats, the application of anthelmintics is often carried out mainly at dosages determined for sheep without knowing the real effects and metabolism features. One of the several anthelmintic classes used against these parasites is (pro) benzimidazoles which are still widely in use in small ruminants in many countries. The objective of this study was to determine (i) the correlation between plasma and tissue or gastrointestinal content dispositions of ricobendazole (RBZ) in goats and (ii) the in vivo exposure of ricobendazole by H. contortus. Ten goats were experimentally infected with 10,000 larvae of H. contortus. Four weeks of post-infection, the animals received RBZ subcutaneously at 5 mg/kg body weight. Two goats were sacrificed per time at 1, 2, 4, 6 and 12 h after drug administration and, blood, bile, urine, liver, lung, muscle and kidney gastrointestinal tissues/fluids were collected. Adult H. contortus were collected from abomasum, and all samples were analysed by HPLC system. Ricobendazole (RBZ) and its sulphone metabolite were extensively excreted by urine and distributed to all tissues and digestive tract, mainly into the abomasum fluid. RBZ concentration in the lung and ABZSO2 in the kidney were relatively higher than those of other tissues, respectively. The parent drug and its metabolite were recovered in both male and female H. contortus. This study indicates that in goats the plasma concentration profiles of RBZ are strongly correlated with those achieved in different target tissues or fluids, which in turn, reflect the amount of drug taken up by parasites.

Comparative pharmacokinetics and bioavailability of albendazole sulfoxide in sheep and goats, and dose-dependent plasma disposition in goats.

BACKGROUND: The aims of this study were to compare the pharmacokinetics of albendazole sulfoxide (ABZ-SO, ricobendazole) in goats and sheep at a dose of 5 g/kg bodyweight (BW), after intravenous (IV) and subcutaneous (SC) administrations, and to investigate the effects of increased doses (10 and 15 mg/kg BW) on the plasma disposition of ABZ-SO in goats following SC administration. A total of 16 goats (Capra aegagrus hircus, eight males and eight females) and 8 sheep (Ovis aries, four males and four females) 12-16 months old and weighing 20-32 kg, were used. The study was designed according to two-phase crossover study protocol. In Phase-1, eight sheep were assigned as Group I and 16 goats were allocated into two groups (Group II and Group III). ABZ-SO was applied to Group I (sheep) and Group II (goats) animals subcutaneously, and to Group III (goats) animals intravenously, all at a dose rate of 5 mg/kg BW. In Phase-2, the sheep in the Group I received ABZ-SO intravenously in a dose of 5 mg/kg BW; the goats in Group II and Group III received ABZ-SO subcutaneously at a dose of 10 mg/kg and 15 mg/kg BW, respectively. Blood samples were collected from the jugular vein at different times between 1 and 120 h after drug administrations. The plasma concentrations of ABZ-SO and its metabolites were analysed by high performance liquid chromatography. RESULTS: In goats, the area under the curve, terminal half-life and plasma persistence of ABZ-SO were significantly smaller and shorter, respectively, compared with those observed in sheep following both IV and SC administrations at a dose of 5 mg/kg BW. On the other side, dose-dependent plasma dispositions of ABZ-SO were observed following SC administration at increased doses (10 and 15 mg/kg) in goats. CONCLUSIONS: Consequently, ABZ-SO might be used at higher doses to provide higher plasma concentration and thus to achieve greater efficacy against the target parasites.

Effects of Oleuropein on Epirubicin and Cyclophosphamide Combination Treatment in Rats

Objectives: Oleuropein is the main bioactive polyphenolic compound in olive leaves, olive, and olive oil. Its anticancer, antioxidant, and antiinflammatory effects have been proven through several in vitro and in vivo studies. This study aimed to explore the effects of oleuropein on cyclophosphamideand epirubicin-induced toxicity in female rats. Materials and Methods: Seven groups containing eight rats in each group were formed. Four cycles of 16 mg/kg/week of cyclophosphamide and 2.5 mg/kg/week of epirubicin were administered to the rats through intraperitoneal injection. Oleuropein (150 mg/kg/week) was simultaneously applied via oral gavage. The effects of oleuropein were examined with hemogram tests in whole blood samples and biochemical analysis in serum samples. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum samples were analyzed through enzyme-linked immunosorbent assay. Subsequently, a comet assay was performed using lymphocyte DNA. The levels of oxidant [i.e., malondialdehyde (MDA)] and antioxidants [i.e., catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD)] were measured in the heart, kidney, and liver tissues. Results: Oleuropein could reduce DNA damage and serum TNF-α and IL-6 levels. It also ameliorated some hemogram and biochemical parameters that deteriorated due to antineoplastic drugs. It increased the amounts of antioxidants (GSH, SOD, and CAT) and reduced the level of MDA in the heart, kidney, and liver tissues. Conclusion: Oleuropein might be a beneficial agent against toxicity caused by the combination treatment of cyclophosphamide and epirubicin. Further studies should be performed to demonstrate the protective effects of oleuropein against antineoplastic induced-toxicity precisely.

The Protective Effect of Rosewater against DNA Damages and Oxidant and Antioxidant Parameters of Rats Exposed to Chlorpyrifos Ethyl.

OBJECTIVE: The aim of this study was to determine both the protective effect of rose water (RW) against DNA damage in the tissues of rats exposed to chlorpyrifos-ethyl (CPE) and RW's effect on the oxidant and antioxidant levels in the blood serum and brain tissues of those same rats. METHODS: In this experimental study, 32 mature male wistar albino rats were divided into 4 groups: group I, control; group II, CPE; group III, RW; and group IV, CPE+RW. The parameters of DNA tail intensity and DNA tail moment were analysed in blood samples by comet assay. Glutathione S-transferase (GST), catalase (CAT), and malondialdehyde (MDA) levels in brain tissues were examined. In blood serum, the levels of melatonin (MT) from 3-nitrotyrosine (3-NT) were determined. RESULTS: In the CPE+RW group, the MDA and 3-NT levels in the brain tissues were significantly reduced (p<0.001), while the MT, GST, and CAT levels were significantly higher (p<0.001) compared to those of the CPE group. When the control and RW groups were compared, the CAT, GST, and MT levels were significantly higher (p<0.001) in the RW group, while the MDA and 3-NT levels were significantly lower (p<0.001). CONCLUSION: In rats, RW had positive effects on oxidant damage created by CPE. Both the DNA tail intensity and DNA tail moment in the CPE group were significantly higher (P<0.001) compared to those measures for the control group.

Effects of xylene and formaldehyde inhalations on oxidative stress in adult and developing rats livers.

In this study, it was aimed to demonstrate the possible oxidative stress caused by exposure of xylene and formaldehyde (HCHO) on liver tissue, and on body and liver weights in adult as well as developing rats. The rats (96 female Sprague-Dawley) were randomly divided into four groups: embryonic day 1 (Group 1), 1-day-old infantile rats (Group 2), 4-week-old rats (Group 3) and adult rats (Group 4). The animals were exposed to gases of technical xylene (300 ppm), HCHO (6 ppm) or technical xylene + HCHO (150 ppm + 3 ppm), 8 hours per day for 6 weeks. Superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) and malondialdehyde (MDA) levels were evaluated. In addition, body and liver weights were determinated. Compared to the control animals, body and liver weights were decreased in the embryonic day 1 group (P < 0.001, P < 0.01, respectively) and the 1-day-old infantile group (P < 0.001). Liver weight was increased in the 4-week-old group (P < 0.01). SOD activities were decreased in the 4-week-old rats exposed to HCHO (P < 0.01). CAT activities increased in the embryonic day 1 group (P < 0.05). GSH levels were decreased in the 1-day-old infantile group (P < 0.01), and MDA levels was increased in the embryonic day 1 group (P < 0.05) as compared with the respective control groups. As to GSH and MDA levels in adult and 4-week-old animals, no statistically significant differences were observed (P > 0.05). The present study indicates that exposures to xylene, HCHO and a mixture of them are toxic to liver tissue, and developing female rats are especially more adversely affected. Furthermore, the results of this study show that adult female rats could better tolerate the adverse effects of these toxic gases.

The effects of lycopene on DNA damage and oxidative stress on indomethacin-induced gastric ulcer in rats.

BACKGROUND AND AIMS: Lycopene, the main antioxidant compound present in tomatoes, has high singlet oxygen- and peroxyl radicals-quenching ability, resulting in protection against oxidative damage in aerobic cell. Indomethacin is a nonsteroidal anti-inflammatory drug, and can promote oxidative damage in gastric tissue. The aim of this study was to investigate the protective effects of lycopene on an indomethacin-induced gastric ulcer model. METHODS: A total of 42 adult male Wistar rats were divided into six groups of seven animals as follows: control, indomethacin, lansoprazole, lycopene 10 mg/kg, lycopene 50 mg/kg and lycopene 100 mg/kg. Gastric ulcers were induced by oral administration of indomethacin, after which the differing doses of lycopene were administered by oral gavage. The efficacy of lycopene was compared with lansoprazole. DNA damage of lymphocytes was measured by comet assay. Activities of superoxide dismutase, catalase and myeloperoxidase, as well as malondialdehyde and glutathione levels were determined in stomach tissue. This tissue was also taken for pathological investigations. The TUNEL method was used to detect apoptotic cells in paraffin sections. RESULTS: The results showed that 100 mg/kg lycopene administration significantly decreased % Tail DNA and Mean Tail Moment in the gastric ulcer group, compared with the other treatment groups. This same dose of lycopene also significantly decreased high malondialdehyde level and myeloperoxidase activity, and increased the activity of antioxidant enzymes (with the exception of catalase) in tissue. Apoptosis rates in the stomachs of the rats correlated with the biochemical and histopathological findings. CONCLUSIONS: These results indicated that lycopene might have a protective effect against indomethacin-induced gastric ulcer and oxidative stress in rats.

The protective effects of vitamin C on the DNA damage, antioxidant defenses and aorta histopathology in chronic hyperhomocysteinemia induced rats.

The aim of this study was to investigate the protective effect of vitamin C towards hyperhomocysteinemia (hHcy) induced oxidative DNA damage using the comet assay. The increase in plasma homocysteine levels is an important risk factor for vascular and cardiovascular diseases through free radical production. This study was also conducted to investigate the histopathological changes in the thoracic aorta and the oxidant/antioxidant status in heart, liver and kidney tissues. Twenty-four adult male Wistar rats were divided as control, hHcy and hHcy+vitamin C group. Chronic hHcy was induced by oral administration of l-methionine (1g/kg/day) for 28 days. Vitamin C was given 150mg/kg/day within the specified days. DNA damage was measured by use of the comet assay in lymphocytes. Levels of malondialdehyde (MDA) and glutathione (GSH) as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in heart, liver and renal tissues. Results show that l-methionine administration significantly increased % Tail DNA and Mean Tail Moment in hHcy group as compared with other groups. Vitamin C treatment significantly decreased the high MDA levels and increased activity of antioxidant enzymes in tissues. Aortic diameter and thickness of aortic elastic laminae were significantly lower in hHcy+vitamin C group. Comet assay can be used for the assessment of primary DNA damage caused by hHcy. Histopathological findings showed that vitamin C may have a preventive effect in alleviating the negative effects of hHcy. Vitamin C might be useful in the prevention of endothelial dysfunction caused by hHcy.

Effects of carprofen and meloxicam on C-reactive protein, ceruloplasmin, and fibrinogen concentrations in dogs undergoing ovariohysterectomy.

OBJECTIVE: To evaluate the effects of perioperative oral administration of carprofen and meloxicam on concentrations of 3 acute-phase proteins in dogs undergoing elective ovariohysterectomy (OVH). ANIMALS: 18 healthy adult anestrous female dogs undergoing elective OVH. PROCEDURES: Dogs were allocated to 3 groups (6 dogs/group). A placebo treatment, carprofen (2.0 mg/kg), or meloxicam (0.2 mg/kg) was orally administered to the dogs of the respective groups. The initial doses were administered 30 minutes before premedication prior to OVH; additional doses were administered once daily for 4 days after surgery. Blood samples were collected 45 minutes before premedication and 4, 8, 12, 24, 36, 48, 72, 96, and 120 hours after the end of OVH; samples were used for measurement of total WBC and neutrophil counts and concentrations of C-reactive protein (CRP), ceruloplasmin, and fibrinogen. RESULTS: Values did not differ significantly among groups for WBC and neutrophil counts, serum concentrations of CRP and ceruloplasmin, and plasma concentrations of fibrinogen. Concentrations of all inflammatory markers, except serum ceruloplasmin, increased significantly following OVH, but in a similar manner for each group. No significant changes were detected in serum ceruloplasmin concentrations over time. CONCLUSIONS AND CLINICAL RELEVANCE: Perioperative administration of both carprofen and meloxicam did not significantly affect the concentrations of CRP, ceruloplasmin, and fibrinogen in dogs undergoing OVH. Thus, use of carprofen or meloxicam should not affect clinical interpretation of results for these 3 acute-phase proteins.

Comparison of in vitro antimicrobial susceptibility in Flavobacterium psychrophilum isolated from rainbow trout fry.

The aim of this study was to demonstrate the presence of Flavobacterium psychrophilum in the west Aegean region of Turkey and to evaluate the in vitro susceptibility of F. psychrophilum (isolated from the fry of rainbow trout Oncorhynchus mykiss) to seven antimicrobial agents, as determined by the disk diffusion and agar dilution methods. A total of 250 rainbow trout fry (weight = 2-5 g; total length = 3-6 cm) were examined, and 20 bacterial isolates were phenotypically identified. Antimicrobial agents included in this investigation were amoxicillin-clavulanic acid (AMC), erythromycin (E), enrofloxacin (ENR), florfenicol (FFC), gentamicin (CN), oxytetracycline (OT), and sulfamethoxazole-trimethoprim (SXT). Disk diffusion and agar dilution methods were performed according to published standards. Minimum inhibitory concentration (MIC) ranges were determined using the agar dilution method for F. psychrophilum isolates. Resistance of F. psychrophilum to CN (disk diffusion method: 70%; agar dilution method: 95%), E (65%; 100%), and SXT (75%; 100%) was high using both methods. Resistance to ENR (10%; 15%) and FFC (25%; 25%) was low with both methods; MIC90 (minimum concentration required to inhibit bacterial growth by 90%) was 4 microg/mL for ENR and 16 microg/mL for FFC. Ninety percent of the F. psychrophilum isolates were resistant to AMC based on the disk diffusion method, while only 15% of isolates showed resistance based on the agar dilution method. For OT, 20% of isolates were resistant based on disk diffusion, while 75% exhibited resistance based on agar dilution. The importance of susceptibility testing when facing an outbreak of F. psychrophilum at a fish farm is obvious; however, the discrepancies between testing methods for AMC and OT require further studies.

Effects of xylene and formaldehyde inhalations on renal oxidative stress and some serum biochemical parameters in rats.

In this study, it was aimed to demonstrate the possible renal oxidative stress and some serum biochemical parameters and their alterations caused by the exposure to xylene and formaldehyde (HCHO) in rats. Weighing 150-200g, 12-week-old, 24 female Sprague-Dawley rats were used. The rats were randomly divided into four groups: Group 1 (control), Group 2 (300-ppm technical xylene), Group 3 (6-ppm HCHO) and Group 4 (150-ppm technical xylene + 3-ppm HCHO). The animals were exposed to gases eight hours per day for six weeks. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, glutathione (GSH) and malondialdehyde (MDA) levels were measured. In addition, serum total protein, albumin, urea and creatinine levels were evaluated. Compared with the control animals, urea levels increased significantly in all groups (P < 0.001). GSH activities and MDA levels increased in xylene and xylene + HCHO groups (P < 0.05). No statistically considerable differences were found in SOD, CAT and GSH-Px activities, total protein, albumin and creatinine levels among all groups (P > 0.05). The present study indicates but not statistically confirms the renal toxicity of the exposures to xylene, HCHO and a mixture of them.