Displaying publications 61 - 73 of 73 in total

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  1. Roy P, Das S, Auddy RG, Mukherjee A
    Int J Nanomedicine, 2014;9:4723-35.
    PMID: 25336950 DOI: 10.2147/IJN.S65262
    Andrographolide (AG) is one of the most potent labdane diterpenoid-type free radical scavengers available from plant sources. The compound is the principal bioactive component in Andrographis paniculata leaf extracts, and is responsible for anti-inflammatory, anticancer, and immunomodulatory activity. The application of AG in therapeutics, however, is severely constrained, due to its low aqueous solubility, short biological half-life, and poor cellular permeability. Engineered nanoparticles in biodegradable polymer systems were therefore conceived as one solution to aid in further drug-like applications of AG. In this study, a cationic modified poly(lactic-co-glycolic) acid nanosystem was applied for evaluation against experimental mouse hepatotoxic conditions. Biopolymeric nanoparticles of hydrodynamic size of 229.7 ± 17.17 nm and ζ-potential +34.4 ± 1.87 mV facilitated marked restoration in liver functions and oxidative stress markers. Superior dissolution for bioactive AG, hepatic residence, and favorable cytokine regulation in the liver tissues are some of the factors responsible for the newer nanosystem-assisted rapid recovery.
    Matched MeSH terms: Drug-Induced Liver Injury/metabolism
  2. Zyoud SH, Awang R, Sulaiman SA, Al-Jabi SW
    Basic Clin Pharmacol Toxicol, 2010 Nov;107(5):887-92.
    PMID: 20456332 DOI: 10.1111/j.1742-7843.2010.00594.x
    Identifying indices of poor prognosis at first presentation after acetaminophen poisoning is the key to both improving clinical care and determining targets for intervention. This study intended to document the prevalence, clinical characteristics and predictors of vomiting and to investigate the relationship between episodes of vomiting at first hospital presentation and outcome in acetaminophen poisoning. This retrospective cohort study included patients who attended the emergency department and were admitted within 24 hr of acetaminophen ingestion. The study was conducted over a period of 5 years from 1 January 2004 to 31 December 2008. Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Data from 291 patients were included. Vomiting was present in 65.3% of patients with acetaminophen poisoning at the time of first presentation. Multiple logistic regression showed that significant risk factors for vomiting were present among patients who reported an ingested dose of acetaminophen ≥10 g (p < 0.001) and a latency time of more than 8 hr (p = 0.030). Overall, an increasing trend in prothrombin time (p = 0.03), serum bilirubin (p < 0.001), serum creatinine (p = 0.005), serum potassium (p < 0.001), length of hospital stay (p < 0.001) and the prevalence of patients who had a serum acetaminophen level above a 'possible toxicity' treatment line (p = 0.001) were associated with an increased number of episodes of vomiting. In conclusion, vomiting was common among patients with acetaminophen poisoning. This study suggests that an increase in episodes of vomiting at first presentation appears to be an important risk marker of subsequent nephrotoxicity and hepatotoxicity.
    Matched MeSH terms: Drug-Induced Liver Injury/etiology
  3. Ng LC, Lee YY, Lee CK, Wong SM
    Int J Dermatol, 2013 Jan;52(1):102-5.
    PMID: 23278617 DOI: 10.1111/j.1365-4632.2011.05436.x
    BACKGROUND: Methotrexate (MTX) is a common and efficacious systemic agent used for the treatment of moderate to severe psoriasis. Nevertheless, its use is associated with the risk of hepatotoxicity. This study was performed to study the association of MTX dose with regards to hepatotoxicity as evidenced by deranged transaminases.
    METHODS: This was a retrospective review of patients with psoriasis on MTX from 2000 to 2009 at the outpatient dermatology clinic, University Malaya Medical Centre (UMMC). We analyzed patients' demography, serial laboratory investigations, liver ultrasounds, and liver biopsies of patients on MTX.
    RESULTS: Sixty-six of 710 (9.30%) patients with psoriasis were prescribed MTX throughout the 10-year period. Among them 57.6% developed deranged transaminases, with six requiring MTX withdrawal due to hepatotoxicity. The mean cumulative dose of MTX at the detection of liver enzyme derangement was 552.3 ± 596.1 mg.
    CONCLUSION: A high proportion of patients on MTX had deranged transaminases. However, the number of serious events was low. We concluded from this study that the use of MTX is relatively safe in patients with moderate to severe psoriasis.

    Study site: outpatient dermatology clinic, University Malaya Medical Centre (UMMC
    Matched MeSH terms: Drug-Induced Liver Injury/etiology*
  4. Jamila N, Khan N, Khan AA, Khan I, Khan SN, Zakaria ZA, et al.
    PMID: 28573253 DOI: 10.21010/ajtcam.v14i2.38
    BACKGROUND: Garcinia hombroniana, known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract.

    MATERIALS AND METHODS: In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl4)/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl4. Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1H, 13C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract.

    RESULTS: In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (p<0.05) potency. In cytotoxicity study, MEA extract was more toxic towards MCF-7 and DBTRG cell lines causing 78.7% and 64.3% cell death, respectively. MEA extract in 1H, 13C-NMR, and IR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents.

    CONCLUSIONS: From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.

    Matched MeSH terms: Drug-Induced Liver Injury/prevention & control*
  5. Salama SM, Abdulla MA, AlRashdi AS, Ismail S, Alkiyumi SS, Golbabapour S
    PMID: 23496995 DOI: 10.1186/1472-6882-13-56
    Hepatology research has focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Thus, this study evaluated mechanisms of the hepatoprotective activity of Curcuma longa rhizome ethanolic extract (CLRE) on thioacetamide-induced liver cirrhosis in rats.
    Matched MeSH terms: Drug-Induced Liver Injury/metabolism; Drug-Induced Liver Injury/pathology; Drug-Induced Liver Injury/prevention & control*
  6. Lakshmanan H, Raman J, Pandian A, Kuppamuthu K, Nanjian R, Sabaratam V, et al.
    Regul Toxicol Pharmacol, 2016 Aug;79:25-34.
    PMID: 27177820 DOI: 10.1016/j.yrtph.2016.05.010
    Senecio candicans DC. (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris, district, Tamil Nadu. The present investigation was carried out to evaluate the sub-chronic toxicity of an aqueous extract of Senecio candicans (AESC) plant in Wistar albino rats. The study was conducted in consideration of the OECD 408 study design (Repeated Dose 90-Day Oral Toxicity Study in Rodents) and the extract was administered via gavage at doses of 250, 500 or 750 mg/kg body weight per day for 90-days. Hematological, biochemical parameters were determined on days 0, 30, 60 and 90 of administration. Animals were euthanized after 90 d treatment and its liver and kidney sections were taken for histological study. The results of sub-chronic study showed significant increase (P liver showed mild mononuclear infiltration in the portal trait, enlarged nucleus around the central vein and mild loss of hepatocyte architecture in rats treated with 750 mg/kg of AESC. Histological examination of kidney showed focal interstitial fibrosis, crowding of glomeruli and mild hydropic change with hypercellular glomeruli in rats treated with 750 mg/kg of AESC. However, no remarkable histoarchitectural change in hepatocytes and glomeruli were observed in rats treated with lower concentrations (250 and 500 mg/kg b.w.) of AESC compared to control group animals. The no-observed adverse effect level (NOAEL) of AESC in the present study was 500 mg/kg b.w. Signs of toxic effects are evident from the current study. Although AESC contains low concentrations of PA, findings from this study suggest that regular consumers of herbal remedies derived from this plant may develop kidney and liver toxicity. Further studies on the isolation and characterization of PAs are necessary to determine the safe dose level of the extract for therapeutic use in traditional medicine.
    Matched MeSH terms: Drug-Induced Liver Injury/blood; Drug-Induced Liver Injury/etiology*; Drug-Induced Liver Injury/pathology
  7. Gnanaraj C, Shah MD, Song TT, Iqbal M
    Biomed Pharmacother, 2017 Aug;92:1010-1022.
    PMID: 28609838 DOI: 10.1016/j.biopha.2017.06.014
    Plants have been consumed in medicinal practices for centuries. Lygodium microphyllum (Cav.) R.Br. (Lygodiaceae), also known as Old World Climbing Fern, is a medicinal plant used by local communities in Sabah for skin and dysentery ailments. This study aims to test aqueous extract of L. microphyllum leaves for hepatoprotective and immunosuppressive activity in rats. Animal studies were carried out to evaluate hepatoprotection of aqueous extract of L. microphyllum at different doses (200, 400 and 600mg/kg b.w.) against carbon tetrachloride (CCl4)-mediated liver injury and histopathological alterations. Total phenolic content in aqueous extract of L. microphyllum leaves was 206.38±9.62mg gallic acid equivalent/g. The inhibitory concentration (IC50) for free radical scavenging activity of L. microphyllum was reached at a concentration of 65μg/ml.L. microphyllum was able to prevent the increase in levels of serum alanine aminotransferase, serum aspartate aminotransferase and hepatic malondialdehyde formation in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal, 8-hydroxydeoxyguanosine) and pro-inflammatory cytokines (Tumor Necrosis Factor-α, Interleukin-6, Prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations showed protective effects by L. microphyllum against CCl4-mediated oxidative stress. Hepatoprotective mechanism of L. microphyllum can be attributed to its antioxidative effects through protection of ultrastructural organelles.
    Matched MeSH terms: Drug-Induced Liver Injury/metabolism; Drug-Induced Liver Injury/pathology; Drug-Induced Liver Injury/prevention & control*
  8. Khan HU, Aamir K, Jusuf PR, Sethi G, Sisinthy SP, Ghildyal R, et al.
    Life Sci, 2021 Jan 15;265:118750.
    PMID: 33188836 DOI: 10.1016/j.lfs.2020.118750
    BACKGROUND: Lipopolysaccharide (LPS) is an endotoxin that leads to inflammation in many organs, including liver. It binds to pattern recognition receptors, that generally recognise pathogen expressed molecules to transduce signals that result in a multifaceted network of intracellular responses ending up in inflammation. Aim In this study, we used lauric acid (LA), a constituent abundantly found in coconut oil to determine its anti-inflammatory role in LPS-induced liver inflammation in Sprague Dawley (SD) rats.

    METHOD: Male SD rats were divided into five groups (n = 8), injected with LPS and thereafter treated with LA (50 and 100 mg/kg) or vehicle orally for 14 days. After fourteen days of LA treatment, all the groups were humanely killed to investigate biochemical parameters followed by pro-inflammatory cytokine markers; tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β. Moreover, liver tissues were harvested for histopathological studies and evaluation of targeted protein expression with western blot and localisation through immunohistochemistry (IHC).

    RESULTS: The study results showed that treatment of LA 50 and 100 mg/kg for 14 days were able to reduce the elevated level of pro-inflammatory cytokines, liver inflammation, and downregulated the expression of TLR4/NF-κB mediating proteins in liver tissues.

    CONCLUSION: These findings suggest that treatment of LA has a protective role against LPS-induced liver inflammation in rats, thus, warrants further in-depth investigation through mechanistic approaches in different study models.

    Matched MeSH terms: Drug-Induced Liver Injury/metabolism
  9. Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al.
    Hepatol Int, 2019 Jul;13(4):353-390.
    PMID: 31172417 DOI: 10.1007/s12072-019-09946-3
    The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.
    Matched MeSH terms: Drug-Induced Liver Injury/etiology
  10. Koh PH, Mokhtar RA, Iqbal M
    Redox Rep, 2011;16(3):134-43.
    PMID: 21801496 DOI: 10.1179/1351000211Y.0000000003
    Andrographis paniculata (hempedu bumi) is a plant that possesses many medicinal values in treating several diseases and for health care maintenance. However, its hepatoprotective activity and mechanism of action have not been fully investigated. Therefore, this study aimed to evaluate the hepatoprotective effects of A. paniculata and its mechanism of action in rats. Carbon tetrachloride (CCl(4)) challenge of rats at a dose of 1.2 ml/kg body weight-induced oxidative stress in the liver. This was evidenced by augmentation in lipid peroxidation, which was accompanied by a decrease in the activities of antioxidant enzymes and depletion in the level of reduced glutathione (P < 0.05). Parrallel to these changes, CCl(4) challenge too, enhanced hepatic damage as evidenced by sharp increase in serum transaminases (e.g. alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) (P < 0.05). Additionally, the impairment of liver function corresponded to histolopathological changes. However, most of these changes were reversed in a dose-dependent fashion by pre-treatment of animals with A. paniculata (P < 0.05). The ability of A. paniculata to scavenge the 2,2-Diphenyl-2-picrylhydrazyl radical was determined through its EC(50) value. The EC(50) value of A. paniculata was 583.60 ± 4.25 µg/ml. In addition, A. paniculata was found to contain 65.37 ± 1.20 mg/g total phenolics expressed as gallic acid equivalent. From these studies, it is concluded that A. paniculata could be used as a hepatoprotective agent and possesses the potential to treat or prevent degenerative diseases where oxidative stress is implicated.
    Matched MeSH terms: Drug-Induced Liver Injury/drug therapy*
  11. Latif IK, Karim AJ, Zuki AB, Zamri-Saad M, Niu JP, Noordin MM
    Poult Sci, 2010 Jul;89(7):1379-88.
    PMID: 20548065 DOI: 10.3382/ps.2009-00622
    Aftermath in several air pollution episodes with high concentrations of polycyclic aromatic hydrocarbons did not significantly affect health and performance of broilers despite its renowned sensitivity to polycyclic aromatic hydrocarbons. The aim of the study was to elucidate the previous lack of response in birds exposed to such severe episodes of air pollution. Benzo[a]pyrene (BaP) was used to simulate the influence of air pollution on hematology, selected organ function, and oxidative stress in broilers. One-day-old chicks were assigned to 5 equal groups composed of a control group, tricaprylin group, and 3 groups treated with BaP (at 1.5 microg, 150 microg, or 15 mg/kg of BW). The BaP was intratracheally administered to 1-d-old chicks for 5 consecutive days. The hematology, liver and kidney function, P450 activity, and malondialdehyde level especially in the group receiving 15 mg of BaP/kg of BW demonstrated evidence of hemato- and hepatoxicity via BaP-induced oxidative stress. The deleterious effect of exposure to high concentration of BaP in broiler chickens was probably due to the anatomy of this species and the half-life of BaP. Although the effect of BaP may be transient or irreversible, pathogen challenges faced during the period of suppression may prove fatal.
    Matched MeSH terms: Drug-Induced Liver Injury/etiology*; Drug-Induced Liver Injury/metabolism
  12. Au A, Aziz Baba A, Goh AS, Wahid Fadilah SA, Teh A, Rosline H, et al.
    Biomed Pharmacother, 2014 Apr;68(3):343-9.
    PMID: 24581936 DOI: 10.1016/j.biopha.2014.01.009
    The introduction and success of imatinib mesylate (IM) has become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, the high efficacy of IM has been hampered by the issue of clinical resistance that might due to pharmacogenetic variability. In the current study, the contribution of three common single nucleotide polymorphisms (SNPs) of ABCB1 (T1236C, G2677T/A and C3435T) and two SNPs of ABCG2 (G34A and C421A) genes in mediating resistance and/or good response among 215 CML patients on IM therapy were investigated. Among these patients, the frequency distribution of ABCG2 421 CC, CA and AA genotypes were significantly different between IM good response and resistant groups (P=0.01). Resistance was significantly associated with patients who had homozygous ABCB1 1236 CC genotype with OR 2.79 (95%CI: 1.217-6.374, P=0.01). For ABCB1 G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with variant TT/AT/AA genotype, compared to other genotype groups (OR=0.48, 95%CI: 0.239-0.957, P=0.03). Haplotype analysis revealed that ABCB1 haplotypes (C1236G2677C3435) was statistically linked to higher risk to IM resistance (25.8% vs. 17.4%, P=0.04), while ABCG2 diplotype A34A421 was significantly correlated with IM good response (9.1% vs. 3.9%, P=0.03). In addition, genotypic variant in ABCG2 421C>A was associated with a major molecular response (MMR) (OR=2.20, 95%CI: 1.273-3.811, P=0.004), whereas ABCB1 2677G>T/A variant was associated with a significantly lower molecular response (OR=0.49, 95%CI: 0.248-0.974, P=0.04). However, there was no significant correlation of these SNPs with IM intolerance and IM induced hepatotoxicity. Our results suggest the usefulness of genotyping of these single nucleotide polymorphisms in predicting IM response among CML patients.
    Matched MeSH terms: Drug-Induced Liver Injury/genetics
  13. Yam MF, Basir R, Asmawi MZ, Ismail Z
    Am J Chin Med, 2007;35(1):115-26.
    PMID: 17265556
    Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.
    Matched MeSH terms: Drug-Induced Liver Injury
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