Metabolization of nifurtimox and benznidazole in cellular fractions of rat mammary tissue

2010 ◽  
Vol 29 (10) ◽  
pp. 813-822 ◽  
Author(s):  
Laura Cecilia Bartel ◽  
María Montalto de Mecca ◽  
Carmen Rodríguez de Castro ◽  
Florencia Matilde Bietto ◽  
José Alberto Castro
Keyword(s):  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Protein Carbonyl ◽  
Reduced Form ◽  
Mammary Tissue ◽  
Intragastric Administration ◽  
Lipid Hydroperoxides ◽  
Sprague Dawley ◽  
Protein Carbonyl Content ◽  
Sprague Dawley Rats ◽  
Protein Sulfhydryl

Two nitroheterocyclic drugs, nifurtimox (NFX) and benznidazole (BZ), used in the treatment of Chagas’ disease have serious side effects attributed to their nitroreduction to reactive metabolites. Here, we report that these drugs reach the mammary tissue and there they could undergo in situ bioactivation. Both were detected in mammary tissue from female Sprague-Dawley rats after their intragastric administration. Only NFX was biotransformed by pure xanthine-oxidoreductase and from tissue cytosol. These activities were purine dependent and were inhibited by allopurinol. Also, only NFX was biotransformed by microsomes in the presence of β-nicotinamide adenine dinucleotide phosphate, reduced form (NADPH), and was inhibited by carbon monoxide and partially by diphenyleneiodonium. NFX treatment produced significant decrease in protein sulfhydryl content after 1, 3 and 6 hours; no increases in protein carbonyl content at any time tested and significantly higher levels of lipid hydroperoxides at 3 and 6 hours; besides, ultrastructural observations after 24 hours showed significant differences in epithelial cells compared to control. These findings indicate that NFX might be more deleterious to mammary tissue than BZ and could correlate with early reports on its ability to promote rat mammary tissue toxicity.

Early nifurtimox-induced biochemical and ultrastructural alterations in rat heart

2007 ◽  
Vol 26 (10) ◽  
pp. 781-788 ◽  
Author(s):  
L.C. Bartel ◽  
M. Montalto de Mecca ◽  
S.L. Fanelli ◽  
C. Rodriguez de Castro ◽  
E.G. Diaz ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Rat Heart ◽  
Microsomal Fraction ◽  
Protein Carbonyl ◽  
Cytochrome P450 Reductase ◽  
Sprague Dawley ◽  
Protein Carbonyl Content ◽  
Ultrastructural Alterations ◽  
Protein Sulfhydryl

Nifurtimox (Nfx) and Benznidazole (Bz) are being used for the treatment of the acute phase of Chagas' disease. Recently, they were also considered for use in the indeterminate phase. Both the nitroheterocyclic drugs have serious toxic side effects. The mechanism of Nfx toxicity is associated with the formation of reactive oxygen species (ROS) generated during nitroreduction. Potential effects on cardiac function have not been established yet, despite the well-known cardiopathy often produced by the disease itself. We describe experiments testing some acute effects of Nfx on the male Sprague Dawley rat heart. Nifurtimox was present in the heart at 1, 3 and 6 h after intragastric (i.g) treatment. In vitro studies on Nfx microsomal and cytosolic nitroreductase activities showed that only the microsomal fraction had the ability to nitroreduce it. Cytochrome P450 and cytochrome P450 reductase would be involved in the process as suggested by their response to specific inhibitors. Nifurtimox increased the cardiac protein carbonyl content at 1 and 3 h and decreased the protein sulfhydryl content at 3 h. In addition, 24 h after treatment ultrastructural alterations such as marked cytoplasmic vacuolization, separation and loss of myofibrils and mitochondrial swelling were observed. Results suggest that Nfx administration might aggravate pre-existing adverse cardiac conditions. Human & Experimental Toxicology (2007) 26, 781 — 788

scholarly journals Simvastatin Attenuates Contrast-Induced Nephropathy through Modulation of Oxidative Stress, Proinflammatory Myeloperoxidase, and Nitric Oxide

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ketab E. Al-Otaibi ◽  
Abdulrahman M. Al Elaiwi ◽  
Mohammad Tariq ◽  
Abdulrahman K. Al-Asmari
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Femoral Vein ◽  
Lipid Hydroperoxides ◽  
Sprague Dawley ◽  
Glycerol Injection ◽  
Sprague Dawley Rats ◽  
Structural Abnormalities ◽  
Nephroprotective Effect

Contrast media- (CM-) induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN). Adult Sprague Dawley rats were divided into seven groups. After 24 h of water deprivation, all the rats except in control and SSTN-only groups were injected (10 ml/kg) with 25% glycerol. After 30 min, SSTN (15, 30, and 60 mg/kg) was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8 ml/kg) through femoral vein over a period of 2 min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels) and myeloperoxidase (MPO) and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity.

scholarly journals The Effects of Trimetazidine and Sildenafil on Bilateral Cavernosal Nerve Injury Induced Oxidative Damage and Cavernosal Fibrosis in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Dogan Atilgan ◽  
Bekir S. Parlaktas ◽  
Nihat Uluocak ◽  
Fikret Erdemir ◽  
Fatma Markoc ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Oxidative Damage ◽  
Nerve Injury ◽  
Rat Model ◽  
Protein Carbonyl ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Collagen Density ◽  
Cavernosal Nerve

Aim. The aim of this study was to compare the effects of sildenafil and trimetazidine on bilateral cavernosal nerve injury-induced oxidative damage and fibrotic changes in cavernosal tissue in rat model.Material and Methods. A total of 32 male Sprague-Dawley rats were randomly divided into 4 groups; each group consist 8 rats (control, BCI, BCI + TMZ, and BCI + sildenafil groups). Tissue superoxide dismutase (SOD), malondialdehyde (MDA), and protein carbonyl (PC) levels were determined biochemically and distribution of cavernosal fibrosis density among groups was performed histopathologically.Results. Tissue SOD levels in BCI group were significantly lower than the control group (P<0.05). Tissue MDA and PC levels in BCI group were significantly higher than the control group (P<0.05). TMZ and sildenafil administration significantly increased tissue SOD levels (P<0.05) and reduced tissue MDA and PC levels (P<0.05). Histologically, the degree of cavernosal fibrosis and collagen density was higher in BCI group in comparison to control, TMZ-treated, and sildenafil-treated groups.Conclusion. BCI caused oxidative damage and increased cavernosal fibrosis in rat penis. TMZ and sildenafil treatment decreased oxidative damage and reduced the degree of fibrosis in penile tissue due to BCI.

Epigallocatechin gallate effectively ameliorates fluoride-induced oxidative stress and DNA damage in the liver of rats

2013 ◽  
Vol 91 (7) ◽  
pp. 528-537 ◽  
Author(s):  
Shanmugam Thangapandiyan ◽  
Selvaraj Miltonprabu
Keyword(s):  
Dna Damage ◽  
Green Tea ◽  
Body Mass ◽  
Radical Scavenging ◽  
Epigallocatechin Gallate ◽  
Thiobarbituric Acid ◽  
Protein Carbonyl ◽  
Health Concern ◽  
Lipid Hydroperoxides ◽  
Protein Carbonyl Content

Environmental exposure to sodium fluoride (NaF) compounds is a worldwide health concern. Epigallocatechin gallate (EGCG) is a green tea catechin found in a variety of green tea preparations. The intention of this study was to investigate the hepatoprotective role of EGCG in NaF-intoxicated rats. Rats were orally treated with NaF alone (25 mg·(kg body mass)−1·day−1) or plus EGCG at different doses (20, 40, and 80 mg·(kg body mass)−1·day−1) for 4 weeks. Hepatotoxicity of NaF was determined by increased levels of serum hepatospecific markers and total bilirubin, along with increased levels of thiobarbituric acid reactive substances, lipid hydroperoxides, protein carbonyl content, and conjugated dienes. The hepatotoxic nature of NaF was further evidenced by the decreased activity of enzymatic and nonenzymatic antioxidant levels in liver. NaF-treated rats also showed increased DNA damage and fragmentation in hepatocytes. Administration of EGCG (40 mg·(kg body mass)−1) to NaF-intoxicated rats significantly recuperated the distorted biochemical indices, DNA damage, and pathological changes in the liver tissue. Thus, the results of the present study clearly demonstrate that EGCG has strong free radical scavenging, antioxidant, and antigenotoxic properties that protect against NaF-induced oxidative hepatic injury in rats.

Potential sources of oxidative stress that induce postexercise proteinuria in rats

2008 ◽  
Vol 104 (4) ◽  
pp. 1063-1068 ◽  
Author(s):  
Günnur Koçer ◽  
Ümit Kemal Şentürk ◽  
Oktay Kuru ◽  
Filiz Gündüz
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Protein Carbonyl ◽  
Exhaustive Exercise ◽  
Carbonyl Content ◽  
Protein Carbonyl Content ◽  
Nadph Oxidase Activity ◽  
Exercise Induced

Exercise-induced proteinuria is a common consequence of physical activity and is caused predominantly by alterations in renal hemodynamics. Although it has been shown that exercise-induced oxidative stress can also contribute to the occurrence of postexercise proteinuria, the sources of reactive oxygen species that promote it are unknown. We investigated the enzymes nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase (XO) as possible sources of oxidative stress in postexercise proteinuria. First, we evaluated the effect of blocking the NADPH oxidase enzyme on postexercise proteinuria. We found a significant increase in urinary protein level, kidney thiobarbituric acid-reactive substances (TBARS), and protein carbonyl content after exhaustive exercise, and NADPH oxidase activity was induced by exercise. Rats that were treated with an NADPH oxidase inhibitor for 4 days before exhaustive exercise showed no increase in kidney TBARS or protein carbonyl derivative level and no proteinuria or NADPH oxidase activation. In the next set of experiments, we investigated the effect of XO blockage on postexercise proteinuria. Oxypurinol, an XO inhibitor was administered to rats for 3 days before exercise. Although XO inhibition significantly decreased kidney TBARS levels and protein carbonyl content in exercised rats, the inhibition did not prevent exercise-induced proteinuria. However, plasma and kidney XO activity was not induced by exercise, but rather it was suppressed under oxypurinol treatment. These results suggest that increased NADPH oxidase activity induced by exhaustive exercise is an important source of elevated oxidative, stress during exercise, which contributes to the occurrence of postexercise proteinuria.

scholarly journals ANTI-CATARACT ACTIVITY OF GARCINIA INDICA AGAINST NAPHTHALENE-INDUCED CATARACT IN RATS

2018 ◽  
Vol 11 (6) ◽  
pp. 208
Author(s):  
Milap R Patel ◽  
Patel Bg
Keyword(s):  
Normal Control ◽  
Corn Oil ◽  
Protein Carbonyl ◽  
Control Group ◽  
Lipid Hydroperoxides ◽  
Enzymatic Antioxidants ◽  
Protein Carbonyl Content ◽  
Group Iii ◽  
Garcinia Indica ◽  
Group I

Objective: The objective of this study is to investigate the anti-cataract activity of the aqueous extract of Garcinia indica (AGI) fruit rinds on naphthalene-induced cataract using rats.Methods: Anti-cataract activity of AGI was evaluated using naphthalene model. Rats were divided into five groups (n=6 in each). Naphthalene solution was prepared by dissolving naphthalene in warm corn oil and administered at the dose of 0.5 g/kg/day p.o. for first 3 days and 1 g/kg/day p.o. thereafter for the induction of cataract. Group I normal control received corn oil 5 ml/kg/day. Group II cataract control received naphthalene solution. Group III received Vitamin E 50 mg/kg/day p.o., and Groups IV and V received AGI 200 mg/kg/day p.o and 400 mg/kg/day p.o., respectively, along with the naphthalene solution for 28 days. At the end of the treatment, levels of malondialdehyde, lipid hydroperoxides (LH), carbonyl and sulfhydryl content, and enzymatic and non-enzymatic antioxidants in lens homogenate were measured.Results: Administration of naphthalene produced a mature cataract and an increase in the opacity index. A significant increase in LH and protein carbonyl content while decrease in protein SH content and antioxidant enzymes was found in naphthalene control group as compared to normal control group. Simultaneous administration of AGI and naphthalene delayed the onset and maturation of cataract.Conclusion: The present investigation suggests that AGI protected the lens against naphthalene-induced oxidative damage which might be responsible for delaying the progression of cataract.

Neonatal Animal Models: Experimental Anencephaly and Similarities to Spina Bifida

1989 ◽  
Vol 8 (5) ◽  
pp. 997-1009
Author(s):  
Michael T. Smith ◽  
L. R. Wood
Keyword(s):  
Animal Models ◽  
Spina Bifida ◽  
Neural Tube ◽  
Developmental Stages ◽  
Neonatal Morbidity ◽  
Intragastric Administration ◽  
Sprague Dawley ◽  
Neural Tubes ◽  
Sprague Dawley Rats ◽  
Autopsy Specimens

Anencephaly and spina bifida are the two most common neural tube defects (NTDs) that occur in humans. They cause considerable fetal wastage and neonatal morbidity and mortality. Numerous animal models have been discovered and have been used to study these malformations. We used the scanning electron microscope (SEM) to compare the development of embryonic stages of spina bifida and anencephaly. Pregnant 180 g Sprague-Dawley rats were given either a 1 ml subcutaneous injection of 1% trypan blue on gestational days 7-8 or an intragastric administration of 75,000 units of vitamin A on gestational days 8-10 to produce embryos with spina bifida or anencephaly. Controls were given vehicle only. The SEM examination of day 9 and 10 embryos revealed no morphologic differences between controls and subjects. Subsequent gestational days showed closure of neural tubes in controls but progressive opening of neural tubes (in the rostral and caudal regions) in experimental subjects. Growth of the dysmorphic neural tube region with subsequent sponteneous necrosis late in gestation resulted in the mature malformations of anencephaly and spina bifida. This study emphasizes the similarities in the developmental stages of spina bifida and anencephaly. We also surveyed a large series of human anencephalic autopsy specimens and noted striking similarities to the animal model.

scholarly journals Tocotrienol Levels in Various Tissues of Sprague-Dawley Rats after Intragastric Administration of Tocotrienols

2002 ◽  
Vol 66 (8) ◽  
pp. 1768-1771 ◽  
Author(s):  
Masaaki OKABE ◽  
Mariko OJI ◽  
Ikuo IKEDA ◽  
Hirofumi TACHIBANA ◽  
Koji YAMADA
Keyword(s):  
Intragastric Administration ◽  
Sprague Dawley ◽  
Sprague Dawley Rats
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