scholarly journals Hepatoprotective Effect of Captopril on Liver Toxicity Induced by High and Low Dose of Paracetamol in Rats:Histological Study

2016 ◽  
Vol 8 (3) ◽  
pp. 92
Author(s):  
Turki M. Al-Shaikh ◽  
Mahmoud M. E. Mudawi ◽  
Abdelhadi Y. A. Yassin ◽  
Rami S. Habeballa ◽  
Vijay R. Chidrawar
Keyword(s):  
Normal Saline ◽  
Low Dose ◽  
Liver Toxicity ◽  
Hepatoprotective Effect ◽  
High Dose ◽  
Over The Counter ◽  
Single Oral Administration ◽  
High Single Dose ◽  
Two Phases ◽  
Histopathological Studies

Many patients may administered medications like captopril (ACE inhibitor) for treatment of chronic diseases and may also take Paracetamol as an Over The Counter (OTC) drug which may interact with captopril. Therefore, the aim of this study is to evaluate of the hepatoprotective effect of captopril on liver toxicity induced by low and high dose of paracetamol in rats. This study was conducted in two phases: first study for low dose of paracetamol (300 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were treated orally either 0.9 % Normal Saline (NS), captopril 20 mg/kg, paracetamol 300 mg/kg or captopril 20 mg/kg plus paracetamol 300 mg/kg for 10 consecutive days. Second study for single high dose of paracetamol (3000 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were pretreated orally either 0.9 % Normal Saline (NS) or captopril 20 mg/kg for 7 consecutive days followed by single oral administration of Paracetamol 3000 mg/kg or normal saline. The administration of Paracetamol or normal saline was performed 24 hours after the last administration of captopril. After 48 hours of hepatic injury induction, the animals were then sacrificed and the liver was removed for histopathological studies. Low dose (300 mg/kg) for 10 days and high single dose (3000 mg/kg) of paracetamol produced hepatotoxic effects. While captopril 20 mg/kg showed marked protection against changes induced by low and high dose of paracetamol on the liver.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

Sorafenib Is Contributing to Salvage Chemotherapy and Is Effective Given Alone for Maintenance in AML FLT3 ITD Patients Relapsing Post Allo Hematopoietic Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5265-5265 ◽  
Author(s):  
Emilia Jaskula ◽  
Janusz Lange ◽  
Mariola Sedzimirska ◽  
Andrzej Lange
Keyword(s):  
Maintenance Therapy ◽  
Low Dose ◽  
Liver Toxicity ◽  
Conflicts Of Interest ◽  
Normal Karyotype ◽  
Salvage Chemotherapy ◽  
Remission Induction ◽  
Comparative Genomic ◽  
High Dose ◽  
Hematopoietic Stem

Abstract Normal karyotype AML patients with FLT3 ITD have a higher risk of relapse than those lacking this mutation (Estey EH, Am J Hematol. 2013). Our comparative genomic hybridization study (77 patients) showed that AML cases with as compared to those without FLT3 ITD had significantly lower number of amplifications or deletions (number of total CNV aberrations: 18±4 vs 51±8, p=0.003). The latter observation in concert with that of others (Thiede, Blood 2002) suggest that FLT3 ITD mutation if present in normal karyotype patients is a key player in the pathogenesis of leukaemia and targeting this mutation may be used successfully in FLT3 ITD positive patients relapsing post HSCT. This was also the case in the two patients presented in this study. Patient UPN 952, male, 53 years old, AML M4 (FAB), normal karyotype, received alloHSCT in 2 CR after completion of two lines of remission induction therapies (first: DA3+7 (Daunorubicin, Ara-C), HAM, high dose Ara-C; second: ICE (IDA, Ara-C, VP-16)) and then promptly transplanted. He relapsed 56 days after transplantation. Patient UPN 938, female, 50 years old, AML, normal karyotype, received as an induction DA 3+7, and for consolidation HAM and high dose Ara-C and completed only one course of the maintenance therapy and transplanted in CR. Both cases were transplanted from unrelated donors (10/10 HLA A, B, C, DR and DQ alleles matched), they received myeloablative conditioning (i.v. Busulfan and Cyclophosphamide) and Cyclosporin A as GvHD prophylaxis. At relapse they received salvage chemotherapy tailored to their biological performance (UPN 938 having Age Adjusted Charlson Comorbidity Index 3 received FLAG and UPN 952 with the index 9, ECOG 3, DA2+5). Both cases received in addition Sorafenib (two times 400 mg per day). The response was prompt and the marrow was free from blasts beginning from 11 day post chemotherapy. UPN 952 received as a maintenance only one course of 6-TG with low dose of Ara-C. Due to the substantial comorbidity and liver toxicity WHO3 further chemotherapy treatment was terminated. The patient was left only on Sorafenib (2 times 200 mg per day). UPN 938 was receiving the maintenance therapy (AML protocol) in 6 – 8 weeks intervals based on low dose Ara-C with 6TG or DNR and also Sorafenib (2 times 200 mg per day). In both cases FLT3 signalling pathway (FLT3 Pathway Mutation PCR Array, SABiosciences, Qiagen) revealed a lack of any additional mutation at the check points in FLT3, KRAS, HRAS, NRAS, MEK1, PIK3CA, BRAF and PTEN genes. UPN 938 had in addition to FLT3 ITD mutation c.1807_1808insATGAATATGATCTCAAAT (p.K602_W603insYEYDLK) insertion which relevance was not so far describe. Sorafenib resistance mutations were not found. The patients were on Sorafenib for 8 (UPN 938) and 9 months (UPN 952). The course of UPN938 was uncomplicated. The second case showed mild aGvHD symptoms evolving into cGvHD (skin lesions and dry eye) slowed down with rapamicine. Up to now the patients are in CR and free from FLT3 ITD. The main observation points: - Sorafenib with chemotherapy tailored to the biologic performance of patients contributes to the efficient salvage in patients with relapsing FLT3 ITD positive AML post HSCT and is also effective given alone as a maintenance. - Side effects were seen in one out of two patients likely associated with the blocking of VEGFR signalling transmission (hand foot skin rash, von Willebrandt factor activity – 388%). Conclusion: The use of multikinase inhibitor (Sorafenib) contributes effectively to salvage therapy in FLT3+ AML patients relapsing post alloHSCTSorafenib given alone is able to maintain long-lasting remissionSide effects are individually dependent Supported by NBiR CellsTherpy grant and Byer Health Care Disclosures No relevant conflicts of interest to declare.

scholarly journals Antidiabetic Activity ofVinca roseaExtracts in Alloxan-Induced Diabetic Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Mohammed Fazil Ahmed ◽  
Syed Mohammed Kazim ◽  
Syed Safiullah Ghori ◽  
Syeda Sughra Mehjabeen ◽  
Shaik Rasheed Ahmed ◽  
...  
Keyword(s):  
Body Weight ◽  
Plant Extract ◽  
Low Dose ◽  
Diabetic Rats ◽  
Antidiabetic Activity ◽  
High Dose ◽  
Vinca Rosea ◽  
Methanolic Extracts ◽  
Whole Plant ◽  
Histopathological Studies

The present study was carried out to evaluate the antidiabetic activity ofVinca roseamethanolic whole plant extracts in alloxan induced diabetic rats for 14 days. The methanolic whole plant extract at high dose (500 mg/kg) exhibited significant anti-hyperglycemic activity than whole plant extract at low dose (300 mg/kg) in diabetic rats. The methanolic extracts also showed improvement in parameters like body weight and lipid profile as well as regeneration ofβ-cells of pancreas in diabetic rats. Histopathological studies reinforce the healing of pancreas, by methanolicVinca roseaextracts, as a possible mechanism of their antidiabetic activity.

Demonstration of the protective effect of ghrelin in the livers of rats with cisplatin toxicity

2021 ◽  
pp. 096032712110267
Author(s):  
R Bademci ◽  
MA Erdoğan ◽  
E Eroğlu ◽  
A Meral ◽  
A Erdoğan ◽  
...  
Keyword(s):  
Toxic Effect ◽  
Low Dose ◽  
Liver Toxicity ◽  
Histopathological Examination ◽  
Normal Liver ◽  
Chemotherapeutic Agents ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Group 2

Despite the various and newly developed chemotherapeutic agents in recent years, cisplatin is still used very frequently as a chemotherapeutic agent, even though cisplatin has toxic effects on many organs. The aim of our study is to show whether ghrelin reduces the liver toxicity of cisplatin in the rat model. Twenty-eight male Sprague Dawley albino mature rats were chosen to be utilized in the study. Group 1 rats (n = 7) were taken as the control group, and no medication was given to them. Group 2 rats (n = 7) received 5 mg/kg/day cisplatin and 1 ml/kg/day of 0.9% NaCl, Group 3 rats (n = 7) received 5 mg/kg/day cisplatin and 10 ng/kg/day ghrelin, Group 4 rats (n = 7) received 5 mg/kg/day cisplatin and 20 ng/kg/day ghrelin for 3 days. Glutathione, malondialdehyde (MDA), superoxide dismutase (SOD), plasma alanine aminotransferase (ALT) levels, and liver biopsy results were measured in rats. It was determined that, especially in the high-dose group, the MDA, plasma ALT, and SOD levels increased less in the ghrelin group as compared to the cisplatin group, and the glutathione level decreased slightly with a low dose of ghrelin, while it increased with a higher dose. In histopathological examination, it was determined that the toxic effect of cisplatin on the liver was reduced with a low dose of ghrelin, and its histopathological appearance was similar to normal liver tissue when given a high dose of ghrelin. These findings show that ghrelin, especially in high doses, can be used to reduce the toxic effect of cisplatin.

scholarly journals HEPATOPROTECTIVE EFFECT OF PERILLYL ALCOHOL (POH) ON HIGH-FAT DIET-LOW-DOSE STREPTOZOTOCIN-INDUCED TYPE 2 DIABETES IN EXPERIMENTAL RATS

2019 ◽  
pp. 266-270
Author(s):  
TOWSEEF HASSAN ◽  
ELANCHEZHIYAN C ◽  
INSHA NASEER
Keyword(s):  
Body Weight ◽  
High Fat Diet ◽  
Low Dose ◽  
Perillyl Alcohol ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Hepatoprotective Effect ◽  
High Fat ◽  
Standard Drug ◽  
Histopathological Studies

Objective: The aim of the present study was to investigate the hepatoprotectivity effect of perillyl alcohol in high-fat diet (HFD)-low-dose streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced in male albino Wistar rats by 4 weeks diet manipulation followed by a low single intraperitoneal injection of STZ (35 mg/kg body weight). Perillyl alcohol was administered orally (50 mg/kg body weight and 100 mg/kg body weight) for 30 days. Glibenclamide was used as a standard drug and given orally 6 mg/kg body weight. At the end of treatment period, levels of alkaline phosphatase (ALP), aspartate transaminase (AST) alanine transaminase (ALT), and bilirubin and serum protein were measured in serum of experimental rats. Histopathological studies of liver were also done with microscope. Results: The levels of ALP, AST ALT, and bilirubin were increased significantly in HFD-STZ-induced diabetic rats. Perillyl alcohol-treated diabetic rats showed marked restoration in the activity of ALP, AST, ALT, and bilirubin when compared with diabetic control rats. Perillyl alcohol and glibenclamide drug-treated rats showed reversible tissue regeneration with prominent hepatocytes. Conclusion: The present results clearly indicate that the perillyl alcohol has a potent efficacy for hepatoprotective effect in HFD- low-dose STZ-induced diabetic rats.

scholarly journals Effectiveness and Toxicity of Methotrexate in Juvenile Idiopathic Arthritis: Comparison of 2 Initial Dosing Regimens

2010 ◽  
Vol 37 (4) ◽  
pp. 870-875 ◽  
Author(s):  
MARA L. BECKER ◽  
CARLOS D. ROSÉ ◽  
RANDY Q. CRON ◽  
DAVID D. SHERRY ◽  
WARREN B. BILKER ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Clinical Response ◽  
Dose Group ◽  
Low Dose ◽  
Liver Toxicity ◽  
High Dose Group ◽  
High Dose ◽  
Active Joint ◽  
Significant Difference ◽  
Dosing Regimens

Objective.To compare the incidence of liver toxicity and clinical response between 2 initial dosing regimens of methotrexate (MTX) for treatment of juvenile idiopathic arthritis (JIA).Methods.Clinical and laboratory data were abstracted from the medical records of 220 children newly prescribed MTX from the same geographic region. One cohort received initial doses of MTX > 0.5 mg/kg/week (“high-dose”) and one cohort received initial doses of MTX ≤ 0.5 mg/kg/week (“low-dose”). Toxicity was defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above the normal range, and positive clinical response was defined as a reduction in active joint count during the first 6 months of MTX therapy.Results.One hundred twenty-six children were in the high-dose MTX group, 94 in the low-dose MTX group. At 6 months, the high-dose group was more likely to have an elevated AST or ALT (adjusted OR 3.89, 95% CI 1.82–8.29, p < 0.0001). Subjects receiving both MTX and nonsteroidal antiinflammatory drugs (NSAID) had no significant difference between groups in change of active joint count, while subjects in the high-dose group but not taking NSAID had more active joints (p = 0.036) at 6 months compared to the low-dose group.Conclusion.Initial high-dose MTX was associated with an increased risk of at least one liver enzyme abnormality with no significant improvement in active joint count. This suggests that there is no apparent benefit, while the potential for liver toxicity is increased, when using higher doses of MTX at treatment inception in patients with JIA.

scholarly journals HYPOGLYCEMIC EFFECTS OF ETHANOLIC FRUIT & LEAVE EXTRACTS OF Solanum incanum (GARDEN EGG) IN STREPTOZOTOCIN-INDUCED DIABETIC WISTAR RATS

2021 ◽  
Author(s):  
Abah Moses Owoicho ◽  
Michael P Okoh ◽  
Lukman Adewale Alli
Keyword(s):  
Blood Glucose ◽  
Normal Saline ◽  
Wistar Rats ◽  
Low Dose ◽  
Aqueous Suspension ◽  
Fasting Blood Glucose ◽  
High Dose ◽  
Fruit Extracts ◽  
Solanum Incanum ◽  
Test Control

This research seeks to assess the hypoglycemic effect of the ethanolic leave and fruit extracts of Solanum incanum instreptozotocin-induced diabetic wistar rats. 200g of each of the extracted powder of fruit and leaf of Solanum incanum will be dissolved in 1600 ml of ethanol in a glass bottlerespectively for a period of 48 hours with intermittent vigorous shaking. The solution will be filteredwith, ASTM (American Society for Testing and Materials) 60 mesh size while the filtrate will becollected and evaporated at 45°C using water bath. The dried concentrate (extract) will then be storedin a sealed transparent bottle for subsequent use. Diabetes will be induced by a single intraperitoneal injection of streptozotocin (120 mg/kg body weight)after 18 hours fast while 5% glucose solution will be administered orally so as to prevent the druginduced hypoglycemic effect of streptozotocin. After 72 hours of streptozotocin injection, bloodsamples will be collected by tail snip method to determine the blood glucose concentrations to confirmthe development of Diabetes Mellitus. Albino rats with fasting blood glucose concentration of greaterthan 126 mg/dl will be considered hyperglycemic and will be selected for the study.The animals will be randomly divided into nine groups each containing five wistar rats while each wistar rat will be marked using black stain. The Non-Diabetic group:Group A: (NORMAL CONTROL/Non-Diabetic Wistar Rats): Will be administered 0.5 ml normalsaline only. On the 7th and 14th days of treatment, the blood glucose levels of the wistar rats will bedetermined using accu-check glucometer, the animals will then be weighed to determine the effect ofthe plant extract on their body weights. The results obtained will then be expressed in g of body weightand mg/d1 of blood respectively. While the Diabetic groups:Group B: (NEGATIVE CONTROL/Untreated Diabetic Wistar Rats): will Serve as diabeticcontrol; receiving 0.5 ml normal saline/day/rat.Group C: (POSITIVE CONTROL/Diabetic Wistar Rats): Will be administered Glibenclamide (10mg/kg b.wt./day) in 0.5 ml normal saline as a fine aqueous suspension orally.Group D 1: (TEST CONTROL Ia /Diabetic Wistar Rats): Will be administered a daily low dose ofethanolic fruit extract of Solanum incanum as a fine aqueous suspension orally in 0.5 ml normal saline. Group D 2: (TEST CONTROL Ib /Diabetic Wistar Rats): Will be administered a daily high dose ofethanolic fruit extract of Solanum incanum as a fine aqueous suspension orally in 0.5 ml normal saline Group E 1: (TEST CONTROL IIa /Dabetic Wistar Rats): Will be administered a daily low dose ofethanolic leaf extract of Solanum incanum as a fine aqueoussuspension orally in 0.5 ml normal salineGroup E 2: (TEST CONTROL IIb /Dabetic Wistar Rats): Will be administered a daily high dose ofethanolic leaf extract of Solanum incanum as a fine aqueoussuspension orally in 0.5 ml normal salineGroup F 1: (TEST CONTROL IIIa /Diabetic Wistar Rats): Will be administered a low dose ofcombined ethanolic leaf and fruit extracts of Solanum incanum as a fine aqueous suspension orally in0.5 ml normal salineGroup F 2: (TEST CONTROL IIIb /Diabetic Wistar Rats): Will be administered a high dose ofcombined ethanolic leaf and fruit extracts of Solanum incanum as a fine aqueous suspension orally in0.5 ml normal salineCollection and treatment of sample:The extracts will be reconstituted in normal saline water and administered orally on daily basis. Theextract group will be treated with high and low doses of the leaf and fruit ethanolic extacts respectively,while the diabetic control and the normal control will be given 0.5 ml of saline water for a period of 14days. At the end of 14 days, the fasting blood glucose levels of all the animals will be taken, afterwhich the animals will be weighed and anaesthetized using chloroform and bled by cardiac puncture24 h after the last treatment. The blood sample will then be collected in plain bottles, allowed to clotand the serum separated by centrifugation for 10 min, which will then be collected and stored at 37℃and finally subjected to biochemical analysis.Biochemical analysis: The serum levels of total cholesterol, triglyceride, High Density Lipoproteinsand Low Density Lipoprotein will be determined by a lipid profile auto analyzer.Statistical analysis: Data will be expressed as mean ± standard deviation. Comparative analysesbetween and amongst variables will be done using analysis of variance (ANOVA). A post hoccomparison (LSD) test will be performed to further ascertain significant differences between means.Statistical significance will be set at P<0.05. All statistical analysis will be done using SPSS.

scholarly journals N-Acetyl cysteine does not prevent liver toxicity from chronic low-dose plus subacute high-dose paracetamol exposure in young or old mice

2016 ◽  
Vol 30 (3) ◽  
pp. 263-275 ◽  
Author(s):  
Alice Elizabeth Kane ◽  
Aniko Huizer-Pajkos ◽  
John Mach ◽  
Catriona McKenzie ◽  
Sarah Jayne Mitchell ◽  
...  
Keyword(s):  
Low Dose ◽  
Liver Toxicity ◽  
High Dose ◽  
Acetyl Cysteine ◽  
Old Mice

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

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