scholarly journals Effect of Experimentally Induced Hepatic and Renal Failure on the Pharmacokinetics of Topiramate in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Kamal M. Matar ◽  
Yasin I. Tayem
Keyword(s):  
Renal Failure ◽  
Pharmacokinetic Profile ◽  
Treated Group ◽  
Time Profile ◽  
Control Group ◽  
Sprague Dawley ◽  
Elimination Phase ◽  
Sprague Dawley Rats ◽  
And Control ◽  
Control Plasma

We aimed to investigate the effect of induced hepatic and renal failure on the pharmacokinetics of topiramate (TPM) in rats. Twenty-four Sprague-Dawley rats were used in this study. Renal or hepatic failure was induced by a single i.p. dose of 7.5 mg/kg cisplatin (n=8) or 0.5 mL/kg carbon tetrachloride (CCl4) (n=8), respectively. Three days after cisplatin dose or 24 h after CCl4dose, the rats were administered a single oral dose of 20 mg/kg TPM. The plasma samples were quantified by LC-MS/MS method. Compared to control, plasma concentration-time profile in CCl4-treated and, to a lesser extent, in cisplatin-treated rats decreased more slowly particularly in the elimination phase. TPM oral clearance (CL/F) in CCl4-treated group was significantly lower than that in control (P<0.001), whereasAUC0−∞, T1/2, and Vd/F were significantly higher in CCl4-treated rats compared to the control (P<0.01). The CL/F was not significantly different between cisplatin-treated rats and control (P>0.05). However, in cisplatin-treated rats, the T1/2 and Vd/F were significantly higher than that in the control group (P<0.01). Both conditions failed to cause a significant effect onCmaxorTmax. The present findings suggest that induced hepatic or renal failure could modify the pharmacokinetic profile of TPM in the rat.

scholarly journals Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation

2012 ◽  
Vol 27 (5) ◽  
pp. 301-305 ◽  
Author(s):  
Baohua Zhu ◽  
Chuanming Tong ◽  
Weitao Guo ◽  
Rong Pu ◽  
Guoping Zhang ◽  
...  
Keyword(s):  
Survival Time ◽  
Hyperacute Rejection ◽  
Cobra Venom ◽  
Control Group ◽  
Sprague Dawley ◽  
Donor Liver ◽  
Cobra Venom Factor ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
And Control

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

scholarly journals Ameliorative effects of Spinacia oleracea on sperm morphology, count, and motility by normalizing the obesity-induced oxidative stress in Sprague Dawley rats

2020 ◽  
Vol 14 (03) ◽  
pp. 124-127
Author(s):  
Somia Iqbal ◽  
Noman Sadiq ◽  
Saad Siddiqui ◽  
Hira Iqbal
Keyword(s):  
Sperm Concentration ◽  
Treated Group ◽  
Sperm Parameters ◽  
Control Group ◽  
Sprague Dawley ◽  
Normal Morphology ◽  
Sprague Dawley Rats ◽  
Group A ◽  
Group B ◽  
Experimental Group

Background: Obesity is a prevailing metabolic disorder that affects the functioning of the male reproductive system. Excessive adipose tissue enhances reactive oxygen species generation and is linked with male infertility. Spinach has demonstrated antioxidant effects. The present study was conducted to determine the antioxidant effects of spinach on sperm parameters in obese Sprague Dawley rats. Subjects and methods: This randomized control study was conducted at the animal house of the National Institute of Health Islamabad, Islamic International Medical College, Cosmesurge International Hospital, Rawalpindi, and Apollo lab, Islamabad, Pakistan from April 2016 to March 2017. Forty male Sprague Dawley rats having an age of 8 weeks and weight 160-200g were tagged from number 1 to 40. Every third rat was randomly allocated to control Group A (n=13) and remaining into the Experimental group (n=27). Rats of control Group A was given a standard diet while a high-fat diet was given to Experimental group rats to induce obesity for the duration of six weeks. Weight (g) was measured weekly and obesity was confirmed when rats attain more than 20% weight when compared with that of rats of control Group A. Then, after obesity induction, the experimental group was alienated into the obesity control group (Group B) and spinach treated group (Group C). For sample, rats of Group A and Group B were sacrificed, and the cauda epididymis of each rat was placed in a Petri dish containing normal saline and cut into pieces to allow the release of sperm and then sperm parameters (sperms concentration, motility, and morphology) were recorded under the microscope. Then, spinach (5% hot water extract) along with the persistence of fat diet was administered to Group C for 4 weeks and finally, sperm parameters were measured in this group. Results: Sperm concentration/ml, motility (%), and normal morphology (%) of Group B rats were significantly decreased as compared to Group A rats. However, sperm concentration/ml, motility (%), and normal morphology (%) of Group C (spinach treated group) rats was significantly increased (p<0.001) as compared to Group B (obesity control group) rats after administering spinach. Conclusion: The addition of Spinach in a normal diet regimen restores normal sperm morphology, improves sperm motility and concentration.

Dexamethasone attenuates reversal of hypertension in one-kidney, one-clip rats

1988 ◽  
Vol 255 (4) ◽  
pp. H717-H721
Author(s):  
H. M. McGowan ◽  
R. Vandongen ◽  
B. Smith
Keyword(s):  
Phospholipase A2 ◽  
Treated Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
The Third ◽  
Serum Thromboxane ◽  
And Control ◽  
Oral Doses ◽  
Prostanoid Synthesis

This study examines the effect of dexamethasone (Dex), a phospholipase A2 inhibitor, on the reversal of 1-kidney, 1-clip (1K,1C) hypertension and the synthesis of phospholipase A2-dependent products. Male Sprague-Dawley 1K,1C hypertensive rats [blood pressure (BP) greater than 190 mmHg] were allocated to three groups: two groups were given daily oral doses of Dex (0.142 mg/kg in water) for 72 h, whereas the third group was given water only (controls). One of the Dex-treated groups was then sham unclipped (n = 9), while the other Dex-treated group (n = 8) and the control group (n = 8) were unclipped. Dex attenuated the BP fall in the unclipped (223 +/- 8-148 +/- 9 mmHg) compared with the control unclipped (226 +/- 9-114 +/- 5 mmHg) animals (P less than 0.005). Aortic 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) was reduced in unclipped Dex-treated rats (13.4 +/- 1.2 ng/mg) compared with unclipped control rats (16.3 +/- 1.4 ng/mg; P less than 0.05) but was higher than in the sham-unclipped Dex group (11.5 +/- 1.2 ng/mg; P less than 0.05). Serum thromboxane B2 (TxB2) in the unclipped Dex-treated group was lower than in the unclipped control rats (P less than 0.05) but higher than in sham-unclipped rats (P less than 0.05). Dex significantly increased urinary prostaglandin E2 (PGE2) excretion, whereas urinary 6-keto-PGF1 alpha was unaltered. After unclipping, both urinary PGE2 and 6-keto-PGF1 alpha increased significantly, although there was no obvious difference between Dex-treated and control animals. These findings demonstrate opposite effects of Dex on renal compared with extrarenal prostanoid synthesis and support the hypothesis that attenuation of aortic 6-keto-PGF1 alpha synthesis may be responsible for the smaller fall in BP after unclipping in Dex-treated rats.

scholarly journals iTRAQ-Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha-1-Antitrypsin as Potential Biomarkers

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yu Yang ◽  
Junmeng Wei ◽  
Xuekuan Huang ◽  
Mingjun Wu ◽  
Zhenbing Lv ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Differentially Expressed ◽  
Coagulation Cascade ◽  
Control Group ◽  
Differentially Expressed Proteins ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Alpha 1 Antitrypsin ◽  
Global Health Problem

Background. Chronic renal failure (CRF) has become a global health problem and bears a huge economic burden. FuShengong Decoction (FSGD) as traditional Chinese medicine has multiple pharmacological effects. Objectives. To understand the underlying molecular mechanism and signaling pathway involved in the FSGD treatment of CRF and screen differentially expressed proteins in rats with CRF treated with FSGD. Methods. Thirty-three male Sprague-Dawley rats were randomly divided into control group, CRF group, and FSGD group. Differentially expressed proteins were screened by iTRAQ coupled with nanoLC-MS/MS, and these identified proteins were later analyzed by GO, KEGG, and STRING. Additionally, haptoglobin (HP) and alpha-1-antitrypsin (AAT) were finally verified by ELISA, Western blot, and real time PCR. Results. A total of 417 proteins were identified. Nineteen differentially expressed proteins were identified in the FSGD group compared with the model group, of which 3 proteins were upregulated and 16 proteins were downregulated. Cluster analysis indicated that inflammatory response was associated with these proteins and complement and coagulation cascade pathways were predominantly involved. The validation methods further confirmed that the levels of HP and AAT were significantly increased. Conclusions. HP and AAT may be the important biomarkers in the pathogenesis of CRF and FSGD therapy.

Role of CD11a and CD11b in ischemic acute renal failure in rats

1994 ◽  
Vol 267 (6) ◽  
pp. F1052-F1058 ◽  
Author(s):  
H. Rabb ◽  
C. C. Mendiola ◽  
J. Dietz ◽  
S. R. Saba ◽  
T. B. Issekutz ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Complete Blood Count ◽  
Leukocyte Adhesion ◽  
Treated Group ◽  
Organ Injury ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Ischemic Acute Renal Failure

Leukocytes, particularly neutrophils, have been implicated in ischemic-reperfusion organ injury (IRI). However, their role in kidney IRI is controversial. Leukocytes express the adhesion molecules CD11/CD18 on their surface, which mediate many functions that can lead to tissue damage. To determine the role of CD11a and CD11b in IRI in the kidney, uninephrectomized Sprague-Dawley rats were pretreated with monoclonal antibodies (MAbs) directed against CD11a and CD11b or control MAbs. The serum creatinine (SCr), complete blood count, and kidney histopathological damage scores (PDS) (scale: 0-4) were assessed prior to and 24 h after 60 min of ischemia. Mean SCr 24 h after ischemia was significantly decreased in the anti-CD11a- and -CD11b-treated group compared with the control MAb-treated group (2.5 +/- 0.3 mg/dl vs. 3.4 +/- 0.2 mg/dl, P <0.05). PDS were also reduced in the CD11a and CD11b group compared with controls (2.7 +/- 0.2 vs. 3.5 +/- 0.1, P < 0.001). These data show that the CD11/CD18 leukocyte adhesion pathway plays a role in mediating ischemic acute renal failure in rats.

scholarly journals Experimental Study of the Effects of Hypoxia Simulator on Osteointegration of Titanium Prosthesis in Osteoporotic Rats

2021 ◽  
Author(s):  
Jiangfeng Liu ◽  
Huijun Kang ◽  
Jiangfeng Lu ◽  
Yike Dai ◽  
Fei Wang
Keyword(s):  
Control Group ◽  
Osteoporotic Bone ◽  
Mrna Levels ◽  
Micro Ct ◽  
Sprague Dawley ◽  
Pull Out ◽  
Sprague Dawley Rats ◽  
Bone To Implant Contact ◽  
Polymerase Chain ◽  
And Control

Abstract Purpose: Poor osseointegration is the key reason for implant failure after arthroplasty, whether in osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine(DFO) can accelerate osteogenesis by activation of the hypoxia signal pathway. The purpose of this study is to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with titanium prosthesis in the bones of osteoporotic rats.Materials and Methods: 90 female sprague-dawley rats were used for the experiment. Ovariectomy and knee arthroplasty were performed. Then, the rats were randomly divided into DFO and control group(n=40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction(PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF and CD31. After 12 weeks, the specimens were examined by micro CT, biomechanics and histopathology to evaluate osteogenesis and osseointegration.Results: The results of PCR showed mRNA levels of VEGF and CD31 in DFO group were significantly higher than those in control group. The immunohistochemistry results indicated positive cell expressions of HIF-1a, VEGF and CD31 in DFO group were also higher. Compared to control group, the microCT parameters of BMD, BV/TV, TB.N, TB.Th were significantly higher. The maximal pull-out force and the bone-to-implant contact (BIC) value were also higher . Conclusions: The local administration of DFO which is used to activate HIF-1a signaling pathway can promote osteogenesis and osseointegration with the prosthesis in osteoporotic bone.

scholarly journals Altered norepinephrine turnover in the brain of rats with chronic renal failure.

1994 ◽  
Vol 4 (11) ◽  
pp. 1901-1907
Author(s):  
R Bigazzi ◽  
E Kogosov ◽  
V M Campese
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Locus Coeruleus ◽  
Turnover Rate ◽  
Nucleus Tractus Solitarius ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Norepinephrine Turnover ◽  
Hypothalamic Nuclei ◽  
And Control

Disturbances of the sympathetic nervous system have been described in chronic renal failure, but their role in the genesis and maintenance of hypertension frequently associated with this condition has not been established. The neuroadrenergic activity in brain nuclei involved in the regulation of blood pressure in uremic animals has also not been previously evaluated. In these studies, the neuroadrenergic activity was measured in the anterior, lateral, and posterior hypothalamic nuclei, in the locus coeruleus, and in the nucleus tractus solitarius of Sprague Dawley rats 5/6 nephrectomized or sham operated 4 wk before the experiments. Neuroadrenergic activity was determined by calculating norepinephrine (NE) turnover rate (in picograms per milligram per hour), 3, 6 and 12 h after inhibition of NE synthesis with L-methyltyrosine. The endogenous NE concentration was significantly greater in the posterior hypothalamic nuclei (21,501 +/- 1,777 pg/mg wet wt) and in the locus coeruleus (16,152 +/- 1,114 pg/mg wet tissue) of uremic compared with control rats (12,213 +/- 1,404 and 7,991 +/- 622 pg/mg wet wt, respectively). On the other hand, the endogenous NE content of the nucleus tractus solitarius and the anterior hypothalamic nuclei did not differ between uremic and control rats. The turnover rate of NE in the posterior hypothalamic nuclei of uremic rats (2150 +/- 430 pg/mg per hour) was significantly faster (P < 0.05) than in control rats (977 +/- 244 pg/mg per hour). The turnover rate of NE in the locus coeruleus of uremic rats (2,584 +/- 323 pg/mg per hour) was also significantly faster than in control animals (400 +/- 140 pg/mg per hour; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Effects of L-Arginine on Liver Damage in Experimental Acute Cholestasis an Immunohistochemical Study

HPB Surgery ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Yucel Ozsoy ◽  
Mustafa Ozsoy ◽  
Teoman Coskun ◽  
Kemal Namlı ◽  
Ahmet Var ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Biliary Obstruction ◽  
Hepatic Tissue ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Duct Ligation ◽  
And Control ◽  
Acute Cholestasis

Obstructive jaundice damages critical functions in the liver. Nitric oxide modulation would influence liver damage induced by biliary obstruction, and little is known about it Acute cholestasis was induced by bile duct ligation (BDL) in two groups of male Sprague-Dawley rats. L-Arginine or serum physiologic was administered to treatment and control group. Histopathological and immunohistochemical iNOS expression was investigated in hepatic tissue. Plasma enzyme activities were increased in acute cholestasis, and that L-arginine treatment partially but significantly prevented the elevation of these markers of liver damage (P< .05). Also histopathology scoring showed that the liver injury was prevented and immunohistochemical iNOS activity was increased significantly in L-arginine group (P< .05). This study shows that, after 7 days of biliary obstruction, liver damage is well established and exogenous L-arginine treatment partially but significantly prevented the liver injury in acute cholestasis.

scholarly journals Acute Toxicity Evaluation of a Crude Sap Isolated from Nypa fruticants Wurmb. in Sprague Dawley Rats

2021 ◽  
Vol 50 (3) ◽  
pp. 711-721
Author(s):  
SITI FATIMAH ROQIAH YAHAYA ◽  
NIZA SAMSUDDIN ◽  
SUHANA MAMAT ◽  
ROZITA HOD ◽  
NOR ZAMZILA ABDULLAH ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Histopathological Examination ◽  
Vital Signs ◽  
Treated Group ◽  
Female Rats ◽  
Full Blood Count ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Significant Difference

Nypa fruticans Wurmb. (nipa palm) sap, locally known as air nira or tuak, is a sweet natural beverage in Malaysia with antioxidant potency beneficial for human health. However, nypa sap lacks scientific attention with no toxicity study has been established. Therefore, this study was performed to evaluate the acute toxicity of nypa sap in the female Sprague Dawley rats. Twenty-five female rats were randomly divided into one control group and four treated groups. Treated groups were orally administered with doses of 5, 50, 300, and 2000 mg/kg of nypa sap, while the control group had received normal saline solution. The animals’ vital signs and mortality were recorded daily at an interval of 30 min and continued up to 14 days. Their blood samples and organs were harvested for toxicity analysis to assess liver and kidney function, lipid profile, and full blood count. The acute toxicity test via measurement of the biochemical and haematological parameters had shown that there was no significant difference between the treated and control groups. However, the blood glucose level in the treated groups (at higher doses of 300 and 2000 mg/kg, respectively) was significantly decreased. A similar trend was recorded for mean corpuscular volume (MCV) albeit in the treated group of 50 mg/kg doses. Histopathological examination of the organs showed no signs of abnormality in both treated and untreated groups. Overall, the results showed that consumption of nypa sap is potentially safe with no acute toxic effect on the laboratory rat models.

scholarly journals Possible Association Between DHEA and PKCε in Hepatic Encephalopathy Amelioration: A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Alessandro Di Cerbo ◽  
Luca Roncati ◽  
Carlotta Marini ◽  
Gianluca Carnevale ◽  
Manuela Zavatti ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Neuroprotective Effect ◽  
Brain Area ◽  
Control Group ◽  
Sprague Dawley ◽  
Kinase C ◽  
Sprague Dawley Rats ◽  
Protein Kinase C Epsilon ◽  
Neuronal Functions ◽  
And Control

Objective: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome caused by liver failure and by an impaired neurotransmission and neurological function caused by hyperammonemia (HA). HE, in turn, decreases the phosphorylation of protein kinase C epsilon (PKCε), contributing to the impairment of neuronal functions. Dehydroepiandrosterone (DHEA) exerts a neuroprotective effect by increasing the GABAergic tone through GABAA receptor stimulation. Therefore, we investigated the protective effect of DHEA in an animal model of HE, and the possible modulation of PKCε expression in different brain area.Methods: Fulminant hepatic failure was induced in 18 male, Sprague–Dawley rats by i.p. administration of 3 g/kg D-galactosamine, and after 30 min, a group of animals received a subcutaneous injection of 25 mg/kg (DHEA) repeated twice a day (3 days). Exploratory behavior and general activity were evaluated 24 h and 48 h after the treatments by the open field test. Then, brain cortex and cerebellum were used for immunoblotting analysis of PKCε level.Results: DHEA administration showed a significant improvement of locomotor activity both 24 and 48 h after D-galactosamine treatment (****p &lt; 0.0001) but did not ameliorate liver parenchymal degeneration. Western blot analysis revealed a reduced immunoreactivity of PKCε (*p &lt; 0.05) following D-galactosamine treatment in rat cortex and cerebellum. After the addition of DHEA, PKCε increased in the cortex in comparison with the D-galactosamine-treated (***p &lt; 0.001) and control group (*p &lt; 0.05), but decreased in the cerebellum (*p &lt; 0.05) with respect to the control group. PKCε decreased after treatment with NH4Cl alone and in combination with DHEA in both cerebellum and cortex (****p &lt; 0.0001). MTS assay demonstrated the synergistic neurotoxic action of NH4Cl and glutamate pretreatment in cerebellum and cortex along with an increased cell survival after DHEA pretreatment, which was significant only in the cerebellum (*p &lt; 0.05).Conclusion: An association between the DHEA-mediated increase of PKCε expression and the improvement of comatose symptoms was observed. PKCε activation and expression in the brain could inhibit GABA-ergic tone counteracting HE symptoms. In addition, DHEA seemed to ameliorate the symptoms of HE and to increase the expression of PKCε in cortex and cerebellum.

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