Safety of Antitheilerial Drug Buparvaquone in Rams

2018 ◽  
Vol 46 (1) ◽  
Author(s):  
Nermin Isik ◽  
Ozlem Derinbay Ekici ◽  
Ceylan Ilhan ◽  
Devran Coskun

 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) 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 > 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) in the level of Tn-I, which is a marker of specific cardiac damage (P < 0.05), whereas there was no statistically (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.Keywords: ram, buparvaquone, safety.

2018 ◽  
Vol 46 (1) ◽  
pp. 7
Author(s):  
Nermin Isik ◽  
Ozlem Derinbay Ekici ◽  
Ceylan Ilhan ◽  
Devran Coskun

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) 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 > 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) in the level of Tn-I, which is a marker of specific cardiac damage (P < 0.05), whereas there was no statistically (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.


1998 ◽  
Vol 17 (3) ◽  
pp. 163-171 ◽  
Author(s):  
Mohammad Iqbal ◽  
Hassan Rezazadeh ◽  
Sabah Ansar ◽  
Mohammad Athar

Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In this communication, we show the modulatory effect of DL-a-tocopherol (Vitamin-E) on ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, toxicity and hyperproliferative response in rats. Fe-NTA-treatment enhances the susceptibility of renal microsomal membrane for iron-ascorbate-induced lipid peroxidation and hydrogen peroxide generation which are accompanied by a decrease in the activities of renal antioxidant enzymes, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood urea nitrogen and serum creatinine has been observed. In addition, Fe-NTA-treatment also enhances renal ornithine decarboxylase activity (ODC) and increases [3H]thymidine incorporation in renal DNA. Prophylactic treatment of animals with Vit.E daily for 1 week prior to the administration of Fe-NTA resulted in the diminution of Fe-NTA-mediated damage. Enhanced susceptibility of renal microsomal membrane for lipid peroxidation induced by iron-ascorbate and hydrogen peroxide generation were significantly reduced (P50.05). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes recovered to significant levels (P50.05). Similarly, the enhanced blood urea nitrogen and serum creatinine levels which are indicative of renal injury showed a reduction of about 50% at a higher dose of Vit.E. The pretreatment of rats with Vit.E reduced the Fe-NTA-mediated induction in ODC activity and enhancement in [3H]thymidine incorporation in DNA. The protective effect of Vit.E was dose dependent. In summary, our data suggest that Vit.E is an effective chemopreventive agent in kidney and may suppress Fe-NTA-induced renal toxicity.


2019 ◽  
Vol 19 (1) ◽  
pp. 15-21
Author(s):  
A Alexandrova ◽  
L Petrov ◽  
R Makaveev ◽  
E Tsvetanova ◽  
A Georgieva ◽  
...  

Aim. The aim of this study was to determine the changes in the erythrocyte oxidative status of the wrestlers after performing the maximal aerobic test, by registering in erythrocytes the levels of lipid peroxidation (LPO), total glutathione (tGSH) and activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). Materials and methods. A group of 12 healthy wrestlers conducted a treadmill maximal aerobic test, and venous blood samples were obtained before and immediately after the exercise. Erythrocytes were separated from plasma and used for spectrophotometric determination of LPO, tGSH and enzyme activities. Plasma was used for determination of hemoglobin concentration (Hb) as an index of hemolysis. Results. The performance of the maximal aerobic test resulted in a significant increase of Hb in blood plasma, a decrease of LPO, and no changes of the tGSH level in erythrocytes. In regards to antioxidant enzymes, our results showed an increase in the activity of GPx, while the CAT and SOD activity remain unchanged. Conclusions. It can be concluded that in active athletes, predominate erythrocytes that are more resistant to oxidative stress, because of the accelerated hemolysis induced by physical exercise, lead to the elimination of the old and oxidative modified cells.


Poljoprivreda ◽  
2021 ◽  
Vol 27 (2) ◽  
pp. 15-24
Author(s):  
Magdalena Matić ◽  
◽  
Rosemary Vuković ◽  
Karolina Vrandečić ◽  
Ivna Štolfa Čamagajevac ◽  
...  

During cultivation, wheat is exposed to several abiotic and/or biotic stress conditions that may adversely impact the wheat yield and quality. The impact of abiotic stress caused by nitrogen deficiency and biotic stress caused by phytopathogenic fungus Fusarium culmorum on biomarkers of oxidative stress in the flag leaf of nine winter wheat varieties (Ficko, U-1, Galloper, BC Mandica, BC Opsesija, Ingenio, Isengrain, Felix, and Bezostaya-1) was analyzed in this study. Hydrogen peroxide concentration and lipid peroxidation level were measured as indicators of oxidative stress, while the antioxidant response was determined by measuring the concentration of phenolic compounds and activities of antioxidant enzymes. Wheat variety and nitrogen treatment had a significant effect on all examined biomarkers of oxidative stress in the flag leaf, while the impact of Fusarium treatment was less pronounced. The most significant impact on the measured stress biomarkers had a low nitrogen level, which mainly increased hydrogen peroxide concentration and lipid peroxidation level and decreased activities of antioxidant enzymes in most varieties. The obtained results were discussed and compared with the previous study in which biochemical analyzes were performed on the wheat spike. There was no significant strong correlation between flag leaf and spike response in the measured parameters, which, in addition to the variety-specific response, also indicates a tissue-specific antioxidant response.


Author(s):  
Aleksandra Vranic ◽  
Aleksandra Antovic ◽  
Nevena Draginic ◽  
Marijana Andjic ◽  
Marko Ravic ◽  
...  

Abstract The aim of this study was to assess oxidative status and to set baseline characteristics for female population with established rheumatoid arthritis. Total of 42 patients with rheumatoid arthritis and 48 age- and sex-matched controls were included in the study. Clinical examination was performed and assessed disease activity. Peripheral blood samples were used for all the assays. The markers of oxidative stress were assessed, including plasma levels of index of lipid peroxidation - thiobarbituric acid reactive substances, hydrogen peroxide, superoxide anion radical, nitrites and activity of superoxide dismutase, catalase and reduced glutathione levels as antioxidant parameters. In the patients group, levels of hydrogen peroxide and index of lipid peroxidation were higher than in controls. Patients with rheumatoid arthritis had decreased superoxide dismutase and catalase activity compared to healthy subjects. Interestingly, controls had higher levels of nitrites compared to patients. Patients showed a marked increase in reactive oxygen species formation and lipid peroxidation as well as decrease in the activity of antioxidant defense system leading to oxidative stress which may contribute to tissue and cartilage damage and hence to the chronicity of the disease.


2013 ◽  
Vol 3 (2) ◽  
pp. 65-70
Author(s):  
Sabah Ansar ◽  
Mohammad Iqbal ◽  
Noura Al Jameil

In this study the effect of butylated hydroxyanisole (BHA), a phenolic antioxidantused in food on Ferric‐Nitrilotriacetate (Fe–NTA) induced nephrotoxicity is reported. Fe‐NTA (9 mg Fe/kg body weight, intraperitoneally) treatment enhanced the renal microsomal lipid peroxidation and hydrogen peroxide generation to ~2‐2.5 folds compared to saline‐treated control and glutathione levels and the activities of antioxidant enzymes decreased to a range of 2–2.5 fold in kidney. These changes were reversed significantly in animals receiving a pretreatment of BHA. Pretreatment with BHA prior to Fe‐ NTA treatment reduced microsomal lipid peroxidation and hydrogen peroxide generation to 1.3‐1.5 fold compared to control group and glutathione and the activities of antioxidant enzymes increased to a range of 1.5‐2 folds in kidney. Fe‐NTA administration enhanced value of blood urea nitrogen and creatinine to 3.7 and 2.5 fold respectively as compared to their corresponding control group. Administration of Fe‐NTA to rats receiving a pretreatment of BHA led to a significant diminution in both of these values. The results indicate that BHA is a potent chemopreventive agent and suppresses Fe‐NTA induced nephrotoxicity in rats.


2017 ◽  
Vol 62 (No. 6) ◽  
pp. 342-350
Author(s):  
CS Lin ◽  
GH Chiang ◽  
CH Liu ◽  
HC Tsai ◽  
CC Yang ◽  
...  

In this study, we report the characterisation of a novel centrifugation and spectrum-integrated veterinary clinical analyser, the AmiShield<sup>TM</sup>, which has been developed for the multiplex measurement of biochemical, electrolyte and immunoassay parameters in a point-of-care testing environment. The aims of this study were to evaluate the analytical performance of the AmiShield<sup>TM</sup> and to compare it with six reference instruments using clinical blood samples. Two hundred and four canine and 120 feline blood samples collected from veterinary teaching hospitals were analysed in parallel using the AmiShield and appropriate reference instruments. All results were evaluated separately for canine and feline specimens. The instrument’s analytical performance was evaluated initially for short- and long-term precision, bias, and observed total error using quality control material. This was followed by comparison of clinical specimens on the AmiShield analyser in parallel with the Vitros and Hitachi for biochemical parameters, VetScan and SNAPshot for total bile acids, and VetLyte and Biolyte for electrolytes. Overall, the AmiShield analyser’s performance met the standards of the American Society for Veterinary Clinical Pathology for total allowable error for most analytes, and can be considered suitable for use in veterinary clinical practices. Using canine samples, excellent correlation coefficients (r ≧ 0.92) were identified for 14 analytes of various categories including glucose, total protein, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, amylase, blood urea nitrogen, creatinine, phosphorus, Na<sup>+</sup>, K<sup>+</sup>, Cl<sup>–</sup> and total bile acid, while good correlations (0.91 ≧ r ≧ 0.80) were recorded for albumin (r = 0.91). Bland-Altman difference plots also showed agreement (greater than 95% within Limits of Agreement) for glucose, total protein, albumin, alanine aminotransferase, alkaline phosphatase, total bilirubin, amylase, blood urea nitrogen, creatinine, Na<sup>+</sup>, K<sup>+</sup>, Cl<sup>–</sup> and total bile acid between AmiShield and the reference instruments. However, aspartate aminotransferase and phosphorus exhibited higher outliers, implying potential problems associated with matrix interferences such as lipemic samples, which warrant further study. This study demonstrates that the AmiShield compares favourably with standard reference instruments, and the new device generated data of high quality for most analytes in clinical canine and feline samples. The capability of reliably measuring multi-category analytes in one device using minute amounts (170 μl) of whole blood and short turn-around times (&lt; 15 min) underlines the high potential of the device as a good alternative in-house diagnostic application.


2010 ◽  
Vol 88 (5) ◽  
pp. 819-834 ◽  
Author(s):  
S. V. Rana ◽  
R. Pal ◽  
K. Vaiphei ◽  
R. P. Ola ◽  
K. Singh

This study evaluates the hepatoprotective effect of carotenoids against isoniazid (INH) and rifampicin (RIF). Thirty-six adult rats were divided into the following 4 groups: (1) control group treated with normal saline; (2) INH + RIF group treated with 50 mg·(kg body mass)–1·day–1 of INH and RIF each; (3) INH + RIF+ carotenoids group treated with 50 mg·(kg body mass)–1·day–1 of INH and RIF each and 10 mg·(kg body mass)–1·day–1 of carotenoids; and (4) carotenoids group treated with 10 mg·(kg body mass)–1·day–1 of carotenoids for 28 days intragastrically. Oxidative stress and antioxidant levels in liver and blood, liver histology and change in transaminases were measured in all the above-mentioned groups. There was an increase in lipid peroxidation with a reduction in thiols, catalase, and superoxide dismutase (SOD) in the liver and blood of rats accompanied by an increase in transaminases, bilirubin, and alkaline phosphatase. Treatment with carotenoids along with INH + RIF partially reversed lipid peroxidation, thiols, catalase, and SOD in the liver and blood of rats. Elevated levels of the enzymes in serum were also reversed partially by this treatment. The degree of necrosis, portal triaditis, and inflammation were also lowered in the carotenoids group. In conclusion, carotenoids supplementation in INH + RIF treated rats showed partial protection.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1766-1766
Author(s):  
Eitan Fibach ◽  
Johnny Amer ◽  
Ada Goldfarb ◽  
Eliezer Rachmilewitz

Abstract In sickle cell anemia (SCD) and thalassemia, although the basic lesions are mutations in the globin genes, the pathophysiology involves oxidative stress-mediated cell damage in the bone marrow (ineffective erythropoiesis due to apoptosis of early erythroid precursors) and in the peripheral blood (chronic hemolysis of mature RBC). In addition, some patients develop thromboembolic complications and recurrent bacterial infections, the etiology of which is related at least in part, to documented oxidative stress in platelets and neutrophils (PMN), respectively. To study the presence and the role of oxidative stress in thalassemia and SCD, we adapted flow cytometry techniques for measuring the generation of Reactive Oxygen Species (ROS), the content of reduced glutathione (GSH), membrane lipid peroxidation and externalization of phosphatidylserine (PS) moieties in RBC, platelets and PMN. Cells derived from the peripheral blood of patients with beta-thalassemia major, intermedia or SCD showed increased oxidative status (increased ROS, lipid peroxidation and PS externalization, and decreased GSH) compared with their normal counterparts. Incubating fresh blood samples from patients with thalassemia major and thalassemia intermedia with 10 mg/ml FPP for 16 hours at 37oC reduced the oxidative status of RBC as well as platelets and PMN. Experiments carried out in normal and thalassemic mice (Th3/+, a mouse model of human beta-thalassemia intermedia demonstrated that mice treated for one week with 10 mg/ml FPP (dissolved in the drinking water) had reduced oxidative stress compared to control mice. The in-vivo effect of FPP was tested on 9 patients with beta-thalassemia (6 - major and 3 - intermedia) treated with 3 gr FPP per os three times a day for 12–15 weeks. Following the treatment, the ROS in RBC, platelets and PMN decreased and the GSH increased in all patients (see table). Six of these patients responded by a modest increase in RBC, reticulocytes and hemoglobin levels. These results suggest that FPP may have an important clinical efficacy as an antioxidant in thalassemia and sickle cell anemia. The in vivo effect of FPP treatment of beta-thalassemia patients Baseline After treatment n Mean ± SE Mean ± SE P-value* * Paired samples t-test RBC 9 324.07 ± 29.19 209.55 ± 23.65 0.001 ROS Platelets 9 223.73 ± 26.49 109.11 ± 8.71 0.001 PMN 9 222.72 ± 46.42 117.61 ± 8.98 0.045 RBC 9 55.37 ± 5.37 94.88 ± 3.71 0.001 GSH Platelets 9 59.41 ± 4.98 97.55 ± 5.26 <0.0001 PMN 9 58.29 ± 5.35 90.06 ± 5.87 0.005


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