scholarly journals Efek pemberian metilprednisolon oral terhadap gambaran histopatologik hati tikus wistar (Rattus norvegicus)

2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Muhammad Rifaldi ◽  
Poppy M. Lintong ◽  
Meilany F. Durry
Keyword(s):  
Liver Injury ◽  
Low Dose ◽  
Clinical Manifestations ◽  
Control Group ◽  
High Dose ◽  
Drug Induced ◽  
Treatment Groups ◽  
Drug Induced Liver Injury ◽  
Histopathological Features ◽  
Group B

Abstract: Drug-induced liver injury (DILI) is an adverse drug reaction which vary in its clinical manifestations, ranging from an asymptomatic increase in liver enzymes to fulminant hepatic failure. Several drugs can cause DILI, one of which is corticosteroid. Methylprednisolone (MT) is a kind of corticosteroid drug which is considered to be a safe drug and it is not believed to cause DILI and often used for the treatment of severe hepatitis. However, there are some reports of DILI in patients treated with high-dose MT. The objectives of this study was to determine the effect of oral administration of MT on liver’s histological changes of witar rats. This study was using 15 rats which were divided into 3 groups; 1 negative control group (group A) and 2 treatment groups (group B and group C). Group B was given a low-dose oral MT, 2 mg/day, while group C was given oral high-dose MT, 4 mg/day for 14 consecutive days. The results showed steatohepatitis features in both low-dose and high-dose MT administration groups. Histopathological features of both treatment groups are similar. Qualitatively, high-dose MT group showed worse histopathological features than the low-dose MT group. Conclusion: Administration of MT by 2mg/day and 4mg/day may induced steatohepatitis in wistar rat’s liver.Keywords: methylprednisolone, liver histopathological features Abstrak: Drug-induced liver injury (DILI) atau cedera hati akibat obat merupakan reaksi efek samping obat dengan manifestasi klinis yang beragam, mulai dari peningkatan enzim-enzim hati yang bersifat asimptomatik sampai dengan timbulnya gagal hati fulminan. Banyak obat-obatan yang dapat menyebabkan DILI, salah satunya adalah golongan kortikosteroid. Metilprednisolon (MT) adalah obat golongan kortikosteroid yang dianggap sebagai obat yang aman dan tidak diyakini dapat menyebabkan DILI, bahkan sering digunakan untuk terapi pasien hepatitis berat. Akan tetapi, beberapa klinisi melaporkan kasus DILI pada pasien-pasien yang diterapi dengan MT dosis tinggi. Penelitian ini bertujuan untuk mengetahui efek pemberian MT oral terhadap perubahan histologik hati tikus wistar. Jenis penelitian yang dilakukan adalah eksperimental laboratorik menggunakan 15 ekor tikus yang dibagi dalam 3 kelompok; 1 kelompok kontrol negatif (kelompok A) dan 2 kelompok perlakuan (kelompok B dan kelompok C). Kelompok B diberikan MT oral dosis rendah sebanyak 2 mg/hari sedangkan kelompok C diberikan MT oral dosis tinggi sebanyak 4 mg/hari setiap hari selama 14 hari berturut-turut. Hasil penelitian menunjukkan gambaran yang sama secara mikroskopik pada kedua kelompok perlakuan yaitu terjadinya steatohepatitis. Tetapi secara kualitatif, kelompok tikus yang mendapatkan MT dosis tinggi memberikan gambaran histopatologik yang lebih jelek dibandingkan kelompok yang diberi dosis rendah. Simpulan: Pemberian metilprednisolon dosis 2mg/hari dan dosis 4 mg/hari dapat mencetuskan terjadinya steatohepatitis pada hati tikus wistar. Kata kunci: metilprednisolon, gambaran histopatologik hati

scholarly journals Nigella sativa can Cure Hepatotoxicity Caused by Pyrazinamide Administration; A Lead from Animal Experiment

2020 ◽  
Vol 34 (1) ◽  
pp. 44-48
Author(s):  
Zunera Hakim
Keyword(s):  
Liver Injury ◽  
Low Dose ◽  
Nigella Sativa ◽  
Control Group ◽  
High Dose ◽  
Multidisciplinary Research ◽  
Medical College ◽  
Group A ◽  
High Doses ◽  
Group B

Introduction: Hepatoxicity is a well known adverse effect of pyrazinamide a commonly used anti tuberculous drug, with no certified remedy. Phytochemicals could be a possible avenue for hepatoprotection. Aims & Objectives: To study the hepatoprotective effect of Nigella sativa in low and high doses on PZA induced liver injury in mice. P lace and duration of study: The study was conducted from April 2017 to June 2017 at Department of Pharmacology and Therapeutics & multidisciplinary research lab, Islamic International Medical College, Rawalpindi. Material & Methods: Sixty white albino mice (male) were divided into four groups randomly. Group A served as control group. Oral Pyrazinamide 500mg/kg/5ml glucose saline suspension was administered for 6 weeks to Group B (hepatotoxic group) alone and to Groups C and D in combination with Nigella sativa in a low dose of 500mg/kg and high dose of 1000mg/kg respectively. The extent of hepatotoxicity was determined by measurement of serum ALT, ALP and GGT. Results: PZA alone resulted in markedly elevated ALT, ALP and GGT (82.8, 319.1 and 37 U/L respectively) as compared to control group i.e (ALT=27.4U/L, ALP=96.4U/L, GGT=9.3U/L). In groups C and D a non-significant increase of biochemical markers i.e, (ALT=38.4±7.89U/L, ALP 185±39.74, GGT24.1±5.89 U/L) and (ALT=36.7U/L, ALP=93.5U/L, GGT=15.8U/L) respectively. Conclusion: Nigella sativa has hepatoprotective effects against PZA induced liver injury in both low and high doses.

High-dose methotrexate-induced reversible grade 4 hyperbilirubinaemia and transaminitis in an adolescent with Burkitt Leukaemia

2021 ◽  
Vol 14 (1) ◽  
pp. e237512
Author(s):  
Sanjeev Khera ◽  
Randhir Ranjan ◽  
Sateesh Ramachandran ◽  
Ajay Beriwal
Keyword(s):  
Liver Injury ◽  
Clinical Significance ◽  
Short Latency ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Drug Induced ◽  
Common Cause ◽  
Drug Induced Liver Injury ◽  
Dose Methotrexate

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.

scholarly journals SUBCHRONIC TOXICITY TEST OF COMBINATION ETHANOL EXTRACT OF DETAM 1 SOYBEAN (GLYCINE MAX L. MERR) AND JATI BELANDA (GUAZUMA ULMIFOLIA LAMK) TOWARD FUNCTION, WEIGHT, AND HISTOPATHOLOGICAL OF WISTAR RAT LIVER

2016 ◽  
Vol 9 (5) ◽  
pp. 197
Author(s):  
Meilinah Hidayat ◽  
Sijani Prahastuti ◽  
Estherolita Dewi ◽  
Dewi Safitri ◽  
Siti Farah Rahmawati ◽  
...  
Keyword(s):  
Liver Function ◽  
Toxicity Test ◽  
Low Dose ◽  
Ethanol Extract ◽  
Good Effect ◽  
Control Group ◽  
High Dose ◽  
Subchronic Toxicity ◽  
Treatment Groups ◽  
Significant Difference

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.

scholarly journals Bicyclol for the treatment of drug-induced liver injury: a propensity score matching analysis using a nationwide inpatient database

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Yongfeng Wang ◽  
Rongtao Lai ◽  
Peilan Zong ◽  
Qingling Xu ◽  
Jia Shang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Statistical Significance ◽  
Control Group ◽  
Time Interval ◽  
Potential Candidate ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Propensity Score Matching Analysis

ObjectiveTo evaluate the efficacy and safety of bicyclol in patients with drug-induced liver injury (DILI) using a nationwide database.MethodsWe retrospectively analyzed the clinical data of DILI patients in the DILI-R database. Propensity score matching was performed to balance the bicyclol and control groups, and alanine aminotransferase (ALT) recovery was compared between the two groups. Factors associated with ALT recovery and safety were identified.ResultsThe analysis included the data of 25,927 patients. Eighty-seven cases were included in the bicyclol group, with 932 cases in the control group. One-to-one propensity score matching created 86 matched pairs. The ALT normalization rate in the bicyclol group was significantly higher than that in the control group (50.00% vs. 24.42%), and statistical significance was found in the superiority test. After adjustment of baseline ALT levels, baseline total bilirubin levels, sex, age, acute or chronic liver diseases, and suspected drugs in the multivariate logic regression analysis, the major influencing factors for ALT recovery included the time interval between ALT tests (days) and the group factor (bicyclol treatment). There were no differences in the proportion of renal function impairment or blood abnormalities between the two groups.ConclusionsBicyclol is a potential candidate for DILI.

Genetic risk factors for drug-induced liver injury in rheumatoid arthritis patients using low-dose methotrexate

2013 ◽  
Vol 14 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Cristina Lucía Dávila-Fajardo ◽  
Jesse J Swen ◽  
José Cabeza Barrera ◽  
Henk-Jan Guchelaar
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Liver Injury ◽  
Genetic Risk ◽  
Low Dose ◽  
Genetic Risk Factors ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Dose Methotrexate

Blood Pressure Lowering Effect of Korea Ginseng Derived Ginseol K-g1

2014 ◽  
Vol 42 (03) ◽  
pp. 605-618 ◽  
Author(s):  
Moo-Yong Rhee ◽  
Belong Cho ◽  
Kwang-Il Kim ◽  
Joohee Kim ◽  
Mi Kyung Kim ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Low Dose ◽  
Favorable Effect ◽  
Control Group ◽  
High Dose ◽  
Blood Pressure Lowering Effect ◽  
Clinical Trial Registration ◽  
Ginseng Extract ◽  
Treatment Groups ◽  
Significant Difference

We investigated the effect of Panax ginseng extract, which is rich in the ginsenoside protopanaxatriol (Ginseol K-g1), on blood pressure (BP). Adults over 20 years old with a systolic BP (SBP) between 120 and 159 mm Hg or a diastolic BP (DBP) between 80 and 99 mm Hg were included. At the end of an initial 2-week washout period, the patients were divided into three groups: the control group (placebo), the low-dose Ginseol K-g1 group (100 mg), and the high-dose Ginseol K-g1 (300 mg) group. The primary end point was the difference in seated SBP (seSBP) and seated DBP (seDBP) changes between the placebo and Ginseol K-g1 groups after 8 weeks of treatment. A total of 90 subjects participated in the study (mean age; 55.2 ± 11.8 years, 43 males). At week 8, levels of seSBP and seDBP were significantly decreased from baseline in the high-dose Ginseol K-g1 group (-3.1 mm Hg and -2.3 mm Hg, respectively, p < 0.05). In contrast, there was no significant decrease in seSBP or seDBP in the control or low-dose Ginseol K-g1 groups. No significant difference of seSBP and seDBP was identified among the three treatment groups at week 8. In patients who had a seSBP ≥ 130 mm Hg or an seDBP ≥ 85 mm Hg, the high dose of Ginseol K-g1 decreased the BP compared with the control group at week 4; however, there was no significant difference at week 8. The proportions of patients who experienced adverse events were comparable among the treatment groups. In conclusion, Ginseol K-g1 has a favorable effect on BP after 4 weeks of treatment, especially at a high dose. However, the effect is not maintained over 8 weeks. (Clinical trial registration information is available at http://www.clinicaltrials.gov , identifier: NCT01483430.)

scholarly journals Relationship between CYP2E1 Gene Polymorphism and Anti-tuberculosis Drug-induced Liver Injury

2018 ◽  
Vol 1 (4) ◽  
pp. 105
Author(s):  
Donglin Zhu ◽  
Yun Xi ◽  
Jieming Dong ◽  
Fanhua Huang ◽  
Changzhi Xu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Gene Polymorphism ◽  
Liver Damage ◽  
Gene Polymorphisms ◽  
Control Group ◽  
Case Group ◽  
Chinese Han ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Cyp2e1 Gene

 Objective: To investigate the relationship between cytochrome P450 E1 (CYP2E1) gene polymorphisms and susceptibility to anti-tuberculosis drug-induced liver damage (ATDLI) in tuberculosis patients in the Chinese Han nationality. Methods: A retrospective analysis was performed on 360 patients with tuberculosis who had liver damage after tuberculosis treatment (case group) and 360 patients with tuberculosis who did not develop liver injury after treatment (control group). MassARRAY were used to detect CYP2E1 gene polymorphisms. Results: In a total of 8 tagged SNP loci selected, the rs8192773 locus failed to pass the test, and therefore, it is not included in subsequent analysis. At the remaining seven SNP sites, the difference in alleles was not statistically significant between the case group and the control group, suggesting that these sites may not be related to liver damage caused by anti-tuberculosis drugs. Three monomer domains were found in the seven tags SNP loci mentioned above. However, it was found that these haplotypes are not closely related to anti-tuberculosis drug-induced liver damage. Conclusion: The CYP2E1 gene polymorphism in the Chinese Han nationality is not related to the occurrence of anti-tuberculosis drug-induced liver injury.

scholarly journals Review: Effect of Red Cabbage Juice (Brassica oleracea var. Capitata f. Rubra) on SGPT Level

2020 ◽  
Vol 3 (1) ◽  
pp. 172-177
Author(s):  
Hesty Wahyuningsih ◽  
Andina Putri Aulia
Keyword(s):  
Liver Injury ◽  
Brassica Oleracea ◽  
Control Group ◽  
Drug Induced ◽  
Red Cabbage ◽  
Drug Induced Liver Injury ◽  
Post Test ◽  
Male Wistar Rats ◽  
Post Hoc ◽  
One Way Anova

Red cabbage (Brassica oleracea var. Capitata f. Rubra) is a vegetable widely used in Indonesian cuisine. Red cabbage is rich in anthocyanins to reduce SGPT levels in drug-induced liver injury (DILI). This study aims to determine the effect of red cabbage juice on SGPT levels in acetaminophen-induced liver injury. In this post-test, only the control group study, male Wistar rats (300g), were randomly divided into 5 groups (K1-K2-K3-K4-K5). Acetaminophen was given to induce liver injury in rats. The rats were treated with the cabbage juice (at the dose of 0.5g/ml or 0.7g/ml or 0.9g/ ml. Data were analyzed using One way ANOVA and LSD post hoc test. Mean SGPT levels for K1, K2, K3, K4, K5 was 58.43 ± 7.18 UI / L, 71.20 ± 9.13 UI/L, 55.73 ± 9.51 UI / L, 72.80 ± 3.47 UI /L, 72.63 ± 3.01 UI /L, respectively. One way ANOVA resulted in p=0.00 (p <0.05). The post hoc LSD test showed significant differences (P <0.05) between all groups except between groups K1-K3, K2-K4, and K2-K5 (p> 0.05). Red cabbage juice can reduce SGPT in acetaminophen-induced liver injury in rats. The most effective dose was 0.5 g/ml.

scholarly journals The Effect of Lactobacillus plantarum BW2013 on The Gut Microbiota in Mice Analyzed by 16S rRNA Amplicon Sequencing

2021 ◽  
Vol 70 (2) ◽  
pp. 235-243
Author(s):  
TONG TONG ◽  
XIAOHUI NIU ◽  
QIAN LI ◽  
YUXI LING ◽  
ZUMING LI ◽  
...  
Keyword(s):  
16S Rrna ◽  
Gut Microbiota ◽  
Dose Group ◽  
Low Dose ◽  
Amplicon Sequencing ◽  
Control Group ◽  
High Dose ◽  
Treatment Groups ◽  
16S Rrna Amplicon Sequencing ◽  
Medium Dose

Lactobacillus plantarum BW2013 was isolated from the fermented Chinese cabbage. This study aimed to test the effect of this strain on the gut microbiota in BALB/c mice by 16S rRNA amplicon sequencing. The mice were randomly allocated to the control group and three treatment groups of L. plantarum BW2013 (a low-dose group of 108 CFU/ml, a medium-dose group of 109 CFU/ml, and a high-dose group of 1010 CFU/ml). The weight of mice was recorded once a week, and the fecal samples were collected for 16S rRNA amplicon sequencing after 28 days of continuous treatment. Compared with the control group, the body weight gain in the treatment groups was not significant. The 16S rRNA amplicon sequencing analysis showed that both the Chao1 and ACE indexes increased slightly in the medium-dose group compared to the control group, but the difference was not significant. Based on PCoA results, there was no significant difference in β diversity between the treatment groups. Compared to the control group, the abundance of Bacteroidetes increased in the low-dose group. The abundance of Firmicutes increased in the medium-dose group. At the genus level, the abundance of Alloprevotella increased in the low-dose group compared to the control group. The increased abundance of Ruminococcaceae and decreased abundance of Candidatus_Saccharimonas was observed in the medium-dose group. Additionally, the abundance of Bacteroides increased, and Alistipes and Candidatus_Saccharimonas decreased in the high-dose group. These results indicated that L. plantarum BW2013 could ameliorate gut microbiota composition, but its effects vary with the dose.

scholarly journals Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges

2021 ◽  
Vol 22 (6) ◽  
pp. 2954
Author(s):  
Alison Jee ◽  
Samantha Christine Sernoskie ◽  
Jack Uetrecht
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Liver Injury ◽  
Clinical Manifestations ◽  
Adaptive Immune System ◽  
Human Leukocyte ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Adaptive Immune

Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Additionally, there is overwhelming evidence that most IDILI is mediated by the adaptive immune system; one example being the association of IDILI caused by specific drugs with specific human leukocyte antigen (HLA) haplotypes, and this may in part explain the idiosyncratic nature of these reactions. The T cell receptor repertoire likely also contributes to the idiosyncratic nature. Although most of the liver injury is likely mediated by the adaptive immune system, specifically cytotoxic CD8+ T cells, adaptive immune activation first requires an innate immune response to activate antigen presenting cells and produce cytokines required for T cell proliferation. This innate response is likely caused by either a reactive metabolite or some form of cell stress that is clinically silent but not idiosyncratic. If this is true it would make it possible to study the early steps in the immune response that in some patients can lead to IDILI. Other hypotheses have been proposed, such as mitochondrial injury, inhibition of the bile salt export pump, unfolded protein response, and oxidative stress although, in most cases, it is likely that they are also involved in the initiation of an immune response rather than representing a completely separate mechanism. Using the clinical manifestations of liver injury from a number of examples of IDILI-associated drugs, this review aims to summarize and illustrate these mechanistic hypotheses.

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