scholarly journals STANDARDIZATION OF MODEL OF INDUCTION OF HEPATOTOXICITY WITH ANTI-TUBERCULOSIS DRUGS IN WISTAR ALBINO RATS

2017 ◽  
Vol 10 (6) ◽  
pp. 150
Author(s):  
Sarita M Kapgate ◽  
Abhijit B Patil
Keyword(s):  
Liver Injury ◽  
Animal Studies ◽  
Hepatic Injury ◽  
Albino Rats ◽  
Histopathological Changes ◽  
First Line ◽  
Drug Induced ◽  
Significant Development ◽  
Reported Study ◽  
Wistar Albino Rats

Objective: The objective of the study to standardize the model of hepatotoxicity induced by ATT drugs in Wistar Albino rats. Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), the first line drugs used in the treatment of tuberculosis (TB) associated with the potential adverse effect. Numerous animal studies were reported endeavoring induction and cure of anti-TB (ATT) drug-induced hepatotoxicity using herbal and chemical drugs. However, the previous reported study failed to replicate where Wistar albino rats were treated with INH, RMP, and PZA and had shown the significant development of liver injury. Hence in present paper, aimed to develop a standardize model of induction of hepatotoxicity with ATT drugs.Methods: Wistar rats were treated with ATT drugs in combination in various doses up to 4-8 weeks. Total nine experiments were conducted to achieve successful hepatotoxicity. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were the biochemical parameters of assessment. Histopathological changes in the liver were also examined.Results: No evidence of any liver injury or an inflammatory infiltrate has been observed as had been reported in the previous studies. Rather decrease in serum ALT levels has been observed by researcher. In short, hepatic injury cannot be developed with the doses used in previous reported papers. The successful attempt to induce hepatotoxicity can be achieved with the doses of INH - 100, RMP - 300, PZA - 700 mg/kg. The findings were confirmed by the raised ALT, AST, and ALP levels compared with baseline. The histopathological changes also support the findings.Conclusion: The dose of INH - 100, RMP – 300 and PZM - 700 mg/kg. Succeeds to induce hepatotoxicity in Wistar albino rats and Swiss albino mice as well.

scholarly journals Drug-Induced Hepatic Injury in Newborns and Children in Intensive Care Unit: A Retrospective Study of China

2021 ◽  
Author(s):  
Ling Ye ◽  
Chengxian Guo ◽  
Zeying Feng ◽  
Longjian Huang ◽  
Chengjun Guo ◽  
...  
Keyword(s):  
Intensive Care ◽  
Liver Injury ◽  
Hepatic Injury ◽  
Sodium Succinate ◽  
Drug Combinations ◽  
Fat Emulsion ◽  
Drug Induced ◽  
Multiple Drugs ◽  
Enzyme Metabolism ◽  
Long Chain

Abstract Purpose Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China. Methods Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). We also collated drug combinations that may affect CYP enzyme metabolism, which may be one of the mechanisms that lead to DILI. Results A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while children’s hepatic injury types were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the assessment by the RUCAM, in newborns, the drugs that were most considered to cause or associated with hepatic injury comprised medium and long chain fat emulsion (17%), sodium glycerophosphate (12%) and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%) and meropenem (8%) are the primary culprit of DILI in children. Drug combinations that may affect CYP enzyme metabolism frequently seen in neonates are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%) and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%) and diazepam + omeprazole (15.3%). Conclusions The drugs that have been found to have hepatotoxicity (meropenem, medium and long chain fat emulsion, ibuprofen.etc.) are also related to DILI in newborns and children. When giving these drugs to newborns and children, physicians need to be more cautious. Also, pay attention to the effect on CYP 450 enzymes when using multiple drugs at the same time.

Pharmacological and Pathological Studies on Taiwan Folk Medicine (IX): The Hepatoprotective Effect of the Methanolic Extract from Echinops Grijisii

1993 ◽  
Vol 21 (01) ◽  
pp. 33-44 ◽  
Author(s):  
Chun-Ching Lin ◽  
Cheng-Hung Lin
Keyword(s):  
Liver Biopsy ◽  
Ethyl Acetate ◽  
Liver Damage ◽  
Methanol Extract ◽  
Methanolic Extract ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
Albino Rats ◽  
Histopathological Changes ◽  
Wistar Albino Rats

In order to isolate the main hepatoprotective component of Echinops grijisii, the crude drug was extracted with methanol and subjected to continuous extractions using n-hexane chloroform, ethyl acetate and n-butanol. The hepatoprotective studies of each fraction from the methanol extract of E. grijisii was conducted in Wistar albino rats with CC14-induced liver damage. Hepatoprotective activity was evaluated in terms of the modification of serum transaminase values such as SGOT and SGPT, and histopathological changes of liver biopsy. The results indicated that the main hepatoprotective component was concentrated in n-butanol and aqueous fractions.

scholarly journals Severe Drug-Induced Liver Injury from Combination Encorafenib/Binimetinib

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Nicholas Gravbrot ◽  
Srinath Sundararajan
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Combination Therapy ◽  
Hepatic Injury ◽  
Mek Inhibitor ◽  
New Combination ◽  
Normal Range ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
First Case

Encorafenib/binimetinib is a new combination BRAF/MEK inhibitor used in the treatment of advanced or metastatic BRAFV600-mutant melanoma. Though generally tolerated well, mild to moderate aminotransferase elevations are common. However, significant liver injury has not been demonstrated in the literature. Here, we report the first case of severe hepatic injury associated with encorafenib/binimetinib in a 58-year-old gentleman requiring admission and extensive workup. He was successfully treated by withdrawing the combination therapy, and liver function returned to normal range.

scholarly journals Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Christine Lin ◽  
Salman R. Khetani
Keyword(s):  
Liver Injury ◽  
Human Liver ◽  
Animal Studies ◽  
Drug Exposure ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Rapid Decline ◽  
Cellular Mechanisms ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions. The latest platforms coculture PHHs with stromal cells to achieve hepatic stability and enable crosstalk between the various liver cell types towards capturing complex cellular mechanisms in DILI. The recent introduction of induced pluripotent stem cell-derived human hepatocyte-like cells can potentially allow a better understanding of interindividual differences in idiosyncratic DILI. Liver models are also being coupled to other tissue models via microfluidic perfusion to study the intertissue crosstalk upon drug exposure as in a live organism. Here, we review the major advances being made in the engineering of liver models and readouts as they pertain to DILI investigations. We anticipate that engineered human liver models will reduce drug attrition, animal usage, and cases of DILI in humans.

The protective and therapeutic effects of linalool against doxorubicin-induced cardiotoxicity in Wistar albino rats

2019 ◽  
Vol 38 (7) ◽  
pp. 803-813 ◽  
Author(s):  
Z Oner ◽  
E Altınoz ◽  
H Elbe ◽  
N Ekinci
Keyword(s):  
Caspase 3 ◽  
Inflammatory Cell ◽  
Cardiac Tissue ◽  
Saline Solution ◽  
Albino Rats ◽  
Therapeutic Effects ◽  
Histopathological Changes ◽  
Treatment Groups ◽  
Wistar Albino Rats ◽  
Plasma Creatine Kinase

The aim of the present study was to determine the protective and therapeutic effects of linalool (LIN) against doxorubicin (DOX)-induced cardiotoxicity in rats histologically and biochemically. In experiments, 64 male Wistar albino rats were randomly divided into eight groups ( n = 8). These groups were control (C) (0.9% saline solution), DOX (20 mg/kg DOX), LIN50 (50 mg/kg LIN), LIN100 (100 mg/kg LIN), DOX + LIN50 (20 mg/kg DOX and 50 mg/kg LIN), DOX + LIN100 (20 mg/kg DOX and 100 mg/kg LIN), LIN50 + DOX (50 mg/kg LIN and 20 mg/kg DOX), and LIN100 + DOX (100 mg/kg LIN and 20 mg/kg DOX). It was determined that necrosis and extensive inflammatory cell infiltration were observed in the DOX group. It was determined that histopathological changes significantly decreased in groups treated with LIN after DOX administration. While the caspase-3 immunostaining was highly evident in DOX group apoptotic cells ( p < 0.001, for all), the intensity of caspase-3 immunostaining in the treatment groups decreased ( p < 0.05). While DOX administration resulted in a significant increase in malondialdehyde (MDA) levels and plasma Creatine kinase (CK) and lactate dehydrogenase (LDH) levels in cardiac tissue when compared to the C groups, it was observed that DOX + LIN administration led to a significant decrease in MDA, plasma CK and LDH levels and a significant increase in glutathione (GSH), superoxide dismutase, and catalase enzyme levels. Finally, it was concluded that DOX led to heavy cardiotoxicity and DOX + LIN administration could remove cardiomyopathy symptoms.

scholarly journals Ascites management by cell-free concentrated ascites reinfusion therapy during recovery from drug-induced acute liver injury: a case report

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Koya Yasuda ◽  
Mea Asou ◽  
Tomohiko Asakawa ◽  
Makoto Araki
Keyword(s):  
Liver Injury ◽  
Liver Regeneration ◽  
Hepatic Injury ◽  
Acute Liver Injury ◽  
Artery Bypass ◽  
Severe Disease ◽  
International Normalized Ratio ◽  
Cardiac Complications ◽  
Massive Ascites ◽  
Drug Induced

Abstract Background The symptoms of drug-induced hepatic injury are manifold; however, the presence of ascites indicates a severe disease condition. The rapid accumulation of ascites is distressing and requires palliative treatment. Because many cases are addressed by repeated large-volume paracentesis, often resulting in impairment due to protein and electrolyte loss, a different approach is required. Case presentation A 61-year-old Japanese man on maintenance dialysis was admitted to our hospital with acute liver injury. Our patient was diagnosed as having drug-induced liver injury due to warfarin or diltiazem, which started immediately after coronary artery bypass grafting 7 months previously. One month after admission, our patient’s hepatic encephalopathy remained grade 1 and his prothrombin time international normalized ratio was maintained at < 1.5. However, the liver was markedly atrophied with massive ascites. Although liver transplantation was desired, he was considered unfit for transplantation because of his renal and cardiac complications. Therefore, we devised a strategy to manage the massive ascites with cell-free concentrated ascites reinfusion therapy while awaiting liver regeneration. At first, cell-free concentrated ascites reinfusion therapy was required frequently because ascites accumulated rapidly. But the fluid retention interval was gradually extended as intended, and cell-free concentrated ascites reinfusion therapy was withdrawn after 8 months. During that time, the size of his liver increased from 1419 cm3 to 1587 cm3 on computed tomography. Conclusions Cell-free concentrated ascites reinfusion therapy is an apheresis therapy in which ascites are collected aseptically by paracentesis, concentrated, and then reinfused intravenously. This treatment has the advantage of preserving nutrition by reusing the fluid. Previously, cell-free concentrated ascites reinfusion therapy was used only for the management of ascites in patients with cirrhosis or carcinomatous peritonitis. This case suggests that palliation and maintenance of nutritional status with cell-free concentrated ascites reinfusion therapy may be useful as an adjunct to liver regeneration in drug-induced hepatic injury.

Beneficial effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin in rats

2015 ◽  
Vol 35 (3) ◽  
pp. 276-281 ◽  
Author(s):  
H Elbe ◽  
Z Dogan ◽  
E Taslidere ◽  
A Cetin ◽  
Y Turkoz
Keyword(s):  
Oxidative Stress ◽  
Renal Injury ◽  
Kidney Tissue ◽  
Albino Rats ◽  
Therapeutic Effects ◽  
Histopathological Changes ◽  
Tubular Atrophy ◽  
Beneficial Effects ◽  
Wistar Albino Rats ◽  
And Oxidative Stress

Ciprofloxacin is a broad-spectrum quinolone antibiotic commonly used in clinical practice. Quercetin is an antioxidant belongs to flavonoid group. It inhibits the production of superoxide anion. In this study, we aimed to evaluate the effects of quercetin on renal injury and oxidative stress caused by ciprofloxacin. Twenty-eight female Wistar albino rats were divided into four groups: control, quercetin (20 mg kg−1 day−1 gavage for 21 days), ciprofloxacin (20 mg kg−1 twice a day intraperitoneally for 10 days), and ciprofloxacin + quercetin. Samples were processed for histological and biochemical evaluations. Malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), and catalase (CAT) activities were measured in kidney tissue. The ciprofloxacin group showed histopathological changes such as infiltration, dilatation in tubules, tubular atrophy, reduction of Bowman’s space, congestion, hemorrhage, and necrosis. In the ciprofloxacin + quercetin group, these histopathological changes markedly reduced. MDA levels increased in the ciprofloxacin group and decreased in the ciptofloxacin + quercetin group. SOD and CAT activities and GSH levels significantly decreased in the ciprofloxacin group. On the other hand, in the ciprofloxacin + quercetin group, SOD and CAT activities and GSH levels significantly increased with regard to the ciprofloxacin group. We concluded that quercetin has antioxidative and therapeutic effects on renal injury and oxidative stress caused by ciprofloxacin in rats.

scholarly journals BIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES OF TRADITIONAL SIDDHA FORMULATION ON CCL4 INDUCED LIVER FIBROSIS IN RATS

2017 ◽  
Vol 9 (7) ◽  
pp. 120
Author(s):  
Diwakar Manickam ◽  
Sri Kamatchi Priya Ramamoorthy ◽  
B. Santhosh Kumar ◽  
Samu Subramaniam ◽  
Shyama Subramaniam
Keyword(s):  
Liver Fibrosis ◽  
Serum Levels ◽  
Control Group ◽  
Albino Rats ◽  
Intragastric Administration ◽  
Free Access ◽  
Equal Proportion ◽  
Histopathological Changes ◽  
Wistar Albino Rats ◽  
Access To Food

ABSTRACTObjective:The main objective of this study is to evaluate therapeutic activity of traditional siddha formulation on CCl4 induced liver fibrosis in rats.Methods:Plant materials collected, shade dried, mixed equal proportion. This mixture was used for extract or kasayam preparation. Twenty four male Wistar albino rats were randomly divided into four groups of six rats each. The normal control group was allowed free access to food and water. Drug control group was allowed to daily intragastric administration of traditional siddha formulation 400mg per kg b.wt per day. Liver damage was performed in the remaining two groups with an i.p.injection of a 1.0 mL/kg b.wt CCl4 and olive oil (2:3 v/v) mixture, twice weekly for 8 weeks. All rats, with the exception of the injury model group, were intragastrically administered traditional siddha formulation (TSF) dosage 400 mg/ kg b.wt /day from 5th week to end of experiment of CCl4 intoxicated rats. The serum levels of hepatic markers and hydroxyproline (Hyp) in the rat livers were measured. Histopathological changes in the liver were assessed for each group using H&E staining and Masson Trichrome examination.Results:Traditional siddha formulation significantly reverse the liver function in CCl4 intoxicated rats correlate with both biochemical and histopathological changesConclusion:Traditional siddha formulation a promising drug for treating liver fibrosis.Keywords: Traditional siddha formulation, Liver fibrosis, CCl4 and Vaithiyars

scholarly journals Crocus sativus L. Extract Containing Polyphenols Modulates Oxidative Stress and Inflammatory Response against Anti-Tuberculosis Drugs-Induced Liver Injury

Plants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 167 ◽  
Author(s):  
Adil Farooq Wali ◽  
Jayachithra Ramakrishna Pillai ◽  
Yusra Al Dhaheri ◽  
Muneeb U. Rehman ◽  
Ambreen Shoaib ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Hepatic Injury ◽  
Standard Dose ◽  
Crocus Sativus ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Response Status ◽  
Crocus Sativus L

The purpose of this study is to analyze the polyphenolic rich extract of Crocus sativus L. petals (CSP) in modulating liver oxidative stress and inflammatory response status against rifampicin isoniazid (INH-RIF) drug-induced liver injury. The INH-RIF was administered for 14 days with varying doses in Wistar rats, while silymarin was administered as standard dose. We report the defensive impacts of CSP against INH-RIF induced liver oxidative stress and proinflammatory cytokine. The CSP treatment at both doses significantly controlled all modulating biochemical hepatic injury indicators and resulted in the attenuation of arbitral INH-RIF damage. The components present in CSP identified by LC–ESI-Q-TOF–MS were found to be flavonoids and fatty acids. It can be inferred that CSP possesses a hepatoprotective capacity against INH-RIF-mediated hepatic injury, which may prove to be a medically beneficial natural product for the management of drug-induced liver injury.

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