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  1. Marzilawati AR, Ngau YY, Mahadeva S
    PMID: 23021009 DOI: 10.1186/2050-6511-13-8
    The metabolism of paracetamol in Asians is thought to differ from Westerners. Detailed clinical features of paracetamol -induced hepatotoxicity among Asians remains largely unreported.
    Matched MeSH terms: Acetaminophen/toxicity*
  2. Zakaria ZA, Sahmat A, Azmi AH, Nur Zainol AS, Omar MH, Balan T, et al.
    BMC Complement Med Ther, 2021 Jan 14;21(1):35.
    PMID: 33446155 DOI: 10.1186/s12906-020-03200-2
    INTRODUCTION: Water-soluble, but not lipid-soluble, extract of Dicranopteris linearis leaves has been proven to possess hepatoprotective activity. The present study aimed to validate the hepatoprotective and antioxidant activities, and phytoconstituents of lipid-soluble (chloroform) extract of D. linearis leaves.

    METHODS: The extract of D. linearis leaves (CEDL; 50, 250 and 500 mg/kg) was orally administered to rats for 7 consecutive days followed by the oral administration of 3 g/kg PCM to induce liver injury. Blood was collected for liver function analysis while the liver was obtained for histopathological examination and endogenous antioxidant activity determination. The extract was also subjected to antioxidant evaluation and phytochemicals determination via phytochemical screening, HPLC and UPLC-HRMS analyses.

    RESULTS: CEDL exerted significant (p 

    Matched MeSH terms: Acetaminophen/toxicity*
  3. Ismail NA, Shamsahal-Din NS, Mamat SS, Zabidi Z, Wan Zainulddin WN, Kamisan FH, et al.
    Pak J Pharm Sci, 2014 Jul;27(4):831-5.
    PMID: 25015448
    The present study aimed to determine the hepatoprotective activity of Dicranopteris linearis L. (family Gleicheniaceae) leaf aqueous extract (DLAE) using two models of liver injury in rats. Rats were divided into ten groups (n=6) and received dH2O (negative control), 200 mg/kg silymarin (positive control) or DLAE (50, 250 and 500 mg/kg) orally once daily for 7 consecutive days and on the 8th day subjected to the hepatotoxic induction either using carbon tetrachloride (CCl4) or paracetamol (PCM). The bloods and livers were collected and subjected to biochemical and microscopical analysis. From the data obtained, only the highest dose of DLAE significantly (P<0.05) reduced the ALP, ALT and AST levels in CCl4-and PCM-induced hepatotoxic rats while the other doses caused significant (P<0.05) reduction only in the levels of ALT and AST. The histological results obtained were in line with the biochemical analysis wherein reduction in the CCl4- and PCM-induced tissue formation of necrosis, steatosis and inflammation occurred in a dose-dependent manner. In conclusion, the DLAE possesses hepatoprotective activity, which could be attributed to its free radicals scavenging and antioxidant activities, and high flavonoids content. Thus, in-depth studies regarding the hepatoprotective activity of DLAE are warranted.
    Matched MeSH terms: Acetaminophen/toxicity*
  4. Nassar I, Pasupati T, Judson JP, Segarra I
    Malays J Pathol, 2010 Jun;32(1):1-11.
    PMID: 20614720 MyJurnal
    Imatinib, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukaemia (CML) and gastrointestinal stromal tumors (GIST). Several fatal cases have been associated with imatinib hepatotoxicity. Acetaminophen, an over-the-counter analgesic, anti-pyretic drug, which can cause hepatotoxicity, is commonly used in cancer pain management. We assessed renal and hepatic toxicity after imatinib and acetaminophen co-administration in a preclinical model. Four groups of male ICR mice (30-35 g) were fasted overnight and administered either saline solution orally (baseline control), imatinib 100 mg/kg orally (control), acetaminophen 700 mg/kg intraperitoneally (positive control) or co-administered imatinib 100 mg/kg orally and acetaminophen 700 mg/kg intraperitoneally (study group), and sacrificed at 15 min, 30 min, 1 h, 2 h, 4 h and 6 h post-administration (n = 4 per time point). The liver and kidneys were harvested for histopathology assessment. The liver showed reversible cell damage like feathery degeneration, microvesicular fatty change, sinusoidal congestion and pyknosis, when imatinib or acetaminophen were administered separately. The damage increased gradually with time, peaked at 2 h but resolved by 4 h. When both drugs were administered concurrently, the liver showed irreversible damage (cytolysis, karyolysis and karyorrhexis) which did not resolve by 6 h. Very minor renal changes were observed. Acetaminophen and imatinib co-administration increased hepatoxicity which become irreversible, probably due to shared P450 biotransformation pathways and transporters in the liver.
    Matched MeSH terms: Acetaminophen/toxicity*
  5. Chua YA, Nurhaslina H, Gan SH
    Methods Find Exp Clin Pharmacol, 2008 Dec;30(10):739-43.
    PMID: 19271022 DOI: 10.1358/mf.2008.30.10.1316830
    Because durian (Durio zibethinus), which is known in Southeast Asia as "the king of fruits", is thought to have special body-warming properties, it should not be consumed with paracetamol due to a risk of toxic effects. The claim of warming properties, however, has not been scientifically proven. This study was conducted to investigate durian's hyperthermic effect and its toxicity when consumed together with paracetamol in rats. Five groups of rats (n=6) were fed with: 1) distilled water (4 ml/250 g), 2) homogenized durian (4 g/250 g), 3) paracetamol solution (2400 mg/kg), 4) durian (4 g/250 g) followed by paracetamol solution (2400 mg/kg), or 5) prazosin solution (15 mg/kg, pregavaged) followed 1 h later by durian (4 g/250 g) and paracetamol solution (2400 mg/kg). Rectal temperature, systolic blood pressure and serum alanine aminotransferase (ALT) levels were taken from each rat at baseline and after the various administrations at 1, 2 and 5 h. Our results showed that the body temperature of rats in the durian-treated group was not significantly elevated when compared to the control. However, there was a significant decrease in body temperature over time in animals from groups 4 and 5. We did not, however, observe a consistent pattern of blood pressure change. Serum chemical analysis for ALT also did not show any significant change in any of the groups. In conclusion, contrary to what some believe, even though durian was found to increase body temperature in some rats, this increment was not significant. Rats receiving the durian-paracetamol combination showed a significant drop in body temperature, which may explain the belief that the two mixtures are toxic. However, the exact mechanism of toxicity is still unknown.
    Matched MeSH terms: Acetaminophen/toxicity*
  6. Vakiloddin S, Fuloria N, Fuloria S, Dhanaraj SA, Balaji K, Karupiah S
    Pak J Pharm Sci, 2015 May;28(3):951-7.
    PMID: 26004728
    The objective of present study was to explore the hepatoprotective and antioxidant profile of Citrullus colocynthis fruits. Hepatoprotective profile of methanolic extract of Citrullus colocynthis fruits (MECCF) was investigated on rats, which were made hepatotoxic using paracetamol. The antioxidant profile of MECCF was evaluated by conducting Catalase, Super oxide Dismutase, Lipid Peroxidation and Diphenyl Picryl Hydrazyl tests. During hepatoprotective investigation, the Paracetamol treated group II showed significant increase in total bilirubin (TB), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP) level. The results so obtained showed that pretreatment of rats with MECCF 300mg/kg p.o. decreases the elevated TB, SGOT, SGPT and ALP serum levels. Also, MECCF inhibitory profile was found comparable with toxicant group (Paracetamol 2g/kg, p.o.). The present study concludes that MECCF fruit possess significant hepatoprotective and antioxidant activity.
    Matched MeSH terms: Acetaminophen/toxicity*
  7. Zakaria ZA, Kamisan FH, Kek TL, Salleh MZ
    Pharm Biol, 2020 Dec;58(1):478-489.
    PMID: 32476526 DOI: 10.1080/13880209.2020.1764058
    Context:Dicranopteris linearis L. (Gleicheniaceae) leaves have been reported to exert hepatoprotective activity.Objective: The hepatoprotective and antioxidant effects of ethyl acetate partition of D. linearis (EADL) are investigated.Materials and methods: EADL was subjected to antioxidant and anti-inflammatory studies, and phytochemical analyses. In vivo study involved six groups (n = 6) of overnight fasted Sprague Dawley rats. The test solutions [10% DMSO (normal), 10% DMSO (negative), 200 mg/kg silymarin (positive) or EADL (50, 250 or 500 mg/kg)] were administered orally once daily for 7 consecutive days followed by oral vehicle (only for normal) or hepatotoxic induction using 3 g/kg paracetamol (PCM).Results: EADL exerted ≈ 90% radical scavenging effects based on the DPPH and superoxide anion radical scavenging assays, high antioxidant capacity in the oxygen radical absorbance capacity assay (≈ 555,000 units), high total phenolic content (≈ 350 mg GAE/100 g extract) (p 
    Matched MeSH terms: Acetaminophen/toxicity*
  8. Zakaria ZA, Kamisan FH, Mohd Nasir N, Teh LK, Salleh MZ
    Nutrients, 2019 Dec 04;11(12).
    PMID: 31817058 DOI: 10.3390/nu11122945
    This study aimed to determine the antioxidant and hepatoprotective activities of semi-purified aqueous partition obtained from the methanol extract of Dicranopteris linearis (AQDL) leaves against paracetamol (PCM)-induced liver intoxication in rats. The test solutions, AQDL (50, 250, and 500 mg/kg), were administered orally to rats (n = 6) once daily for seven consecutive days followed by the hepatotoxicity induction using 3 g/kg PCM (p.o.). Blood was collected for serum biochemical parameters analysis while the liver was collected for histopathological examination and endogenous antioxidant enzymes analysis. AQDL was also subjected to antioxidant determination and phytochemical analysis. Results obtained show that AQDL possessed high total phenolic content (TPC) value and remarkable radical scavenging activities. AQDL also significantly (p < 0.05) reduced the liver weight/body weight (LW/BW) ratio or serum level of ALT, AST, and total bilirubin while significantly (p < 0.05) increase the level of superoxide dismutase (SOD) and catalase (CAT) without affecting the malondialdehyde (MDA) in the liver indicating its hepatoprotective effect. Phytoconstituents analyses showed only the presence of saponins and triterpenes, but lack of flavonoids. In conclusion, AQDL exerts hepatoprotective activity via its high antioxidant potential and ability to modulate the endogenous enzymatic antioxidant defense system possibly via the synergistic action of saponins and triterpenes.
    Matched MeSH terms: Acetaminophen/toxicity*
  9. Gupta G, Chellappan DK, Kikuchi IS, Pinto TJA, Pabreja K, Agrawal M, et al.
    J Environ Pathol Toxicol Oncol, 2017;36(2):113-119.
    PMID: 29199592 DOI: 10.1615/JEnvironPatholToxicolOncol.2017019457
    Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Significant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential.
    Matched MeSH terms: Acetaminophen/toxicity*
  10. Sasidharan S, Aravindran S, Latha LY, Vijenthi R, Saravanan D, Amutha S
    Molecules, 2010 Jun 23;15(6):4478-89.
    PMID: 20657455 DOI: 10.3390/molecules15064478
    BACKGROUND: The objective of this study was to investigate the antioxidant and hepatoprotective effects of methanolic extracts of L. edodes and the determination of their total phenolics content.

    RESULTS: The amount of total phenolics was estimated to be 70.83 mg Gallic Acid Equivalent (GAE) per gram of dry extract. The antioxidant activity of the L. edodes extract was 39.0% at a concentration of 1 mg/mL and was also concentration dependant, with an EC(50) value of 4.4 mg/mL. Different groups of animals (Wister albino mice) were administered paracetamol (1 g/kg, p.o.). L. edodes extract at a dose of 200 mg/kg was administered to the paracetamol treated mice for seven days. The effects of L. edodes extract on serum transaminases (SGOT, SGPT), alkaline phosphatase (ALP) and bilirubin were measured in the paracetamol-induced hepatotoxic mice. L. edodes extract produced significant (p < 0.05) hepatoprotective effects by decreasing the activity of serum enzymes and bilirubin.

    CONCLUSIONS: From these results, it was suggested that L. edodes extract could perhaps protect liver cells from paracetamol-induced liver damage by its antioxidative effect on hepatocytes, hence diminishing or eliminating the harmful effects of toxic metabolites of paracetamol.

    Matched MeSH terms: Acetaminophen/toxicity*
  11. Mamat SS, Kamarolzaman MF, Yahya F, Mahmood ND, Shahril MS, Jakius KF, et al.
    PMID: 24267313 DOI: 10.1186/1472-6882-13-326
    Melastoma malabathricum L. (Melastomaceae) is a small shrub with various medicinal uses. The present study was carried out to determine the hepatoprotective activity of methanol extract of M. malabathricum leaves (MEMM) against the paracetamol-induced liver toxicity in rats model.
    Matched MeSH terms: Acetaminophen/toxicity
  12. Abdul Hamid Z, Budin SB, Wen Jie N, Hamid A, Husain K, Mohamed J
    J Zhejiang Univ Sci B, 2012 Mar;13(3):176-85.
    PMID: 22374609 DOI: 10.1631/jzus.B1100133
    Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. In this study, the effects of ethyl acetate extract of Zingiber zerumbet rhizome [200 mg per kg of body weight (mg/kg) and 400 mg/kg] on PCM-induced nephrotoxicity were examined. Rats were divided into five groups containing 10 rats each. The control group received distilled water while other groups were treated with extract alone (400 mg/kg), PCM alone (750 mg/kg), 750 mg/kg PCM+200 mg/kg extract (PCM+200-extract), and 750 mg/kg PCM+400 mg/kg extract (PCM+400-extract), respectively, for seven consecutive days. The Z. zerumbet extract was given intraperitoneally concurrent with oral administration of PCM. Treatment with Z. zerumbet extract at doses of 200 and 400 mg/kg prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (P<0.05) level of plasma creatinine, plasma and renal malondialdehyde (MDA), plasma protein carbonyl, and renal advanced oxidation protein product (AOPP). Furthermore, both doses were also able to induce a significant increment (P<0.05) of plasma and renal levels of glutathione (GSH) and plasma superoxide dismutase (SOD) activity. The nephroprotective effects of Z. zerumbet extract were confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findings. Moreover, Z. zerumbet extract administered at 400 mg/kg was found to show greater protective effects than that at 200 mg/kg. In conclusion, ethyl acetate extract of Z. zerumbet rhizome has a protective role against PCM-induced nephrotoxicity and the process is probably mediated through its antioxidant properties.
    Matched MeSH terms: Acetaminophen/toxicity*
  13. Akhter S, Basirun WJ, Alias Y, Johan MR, Bagheri S, Shalauddin M, et al.
    Anal Biochem, 2018 06 15;551:29-36.
    PMID: 29753720 DOI: 10.1016/j.ab.2018.05.004
    In the present study, a nanocomposite of f-MWCNTs-chitosan-Co was prepared by the immobilization of Co(II) on f-MWCNTs-chitosan by a self-assembly method and used for the quantitative determination of paracetamol (PR). The composite was characterized by field emission scanning electron microscopy (FESEM) and energy dispersive x-ray analysis (EDX). The electroactivity of cobalt immobilized on f-MWCNTs-chitosan was assessed during the electro-oxidation of paracetamol. The prepared GCE modified f-MWCNTs/CTS-Co showed strong electrocatalytic activity towards the oxidation of PR. The electrochemical performances were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). Under favorable experimental conditions, differential pulse voltammetry showed a linear dynamic range between 0.1 and 400 μmol L-1 with a detection limit of 0.01 μmol L-1 for the PR solution. The fabricated sensor exhibited significant selectivity towards PR detection. The fabricated sensor was successfully applied for the determination of PR in commercial tablets and human serum sample.
    Matched MeSH terms: Acetaminophen/toxicity
  14. Mohamad NE, Yeap SK, Beh BK, Ky H, Lim KL, Ho WY, et al.
    BMC Complement Altern Med, 2018 Jun 25;18(1):195.
    PMID: 29940935 DOI: 10.1186/s12906-018-2199-4
    BACKGROUND: Coconut water has been commonly consumed as a beverage for its multiple health benefits while vinegar has been used as common seasoning and a traditional Chinese medicine. The present study investigates the potential of coconut water vinegar in promoting recovery on acetaminophen induced liver damage.

    METHODS: Mice were injected with 250 mg/kg body weight acetaminophen for 7 days and were treated with distilled water (untreated), Silybin (positive control) and coconut water vinegar (0.08 mL/kg and 2 mL/kg body weight). Level of oxidation stress and inflammation among treated and untreated mice were compared.

    RESULTS: Untreated mice oral administrated with acetaminophen were observed with elevation of serum liver profiles, liver histological changes, high level of cytochrome P450 2E1, reduced level of liver antioxidant and increased level of inflammatory related markers indicating liver damage. On the other hand, acetaminophen challenged mice treated with 14 days of coconut water vinegar were recorded with reduction of serum liver profiles, improved liver histology, restored liver antioxidant, reduction of liver inflammation and decreased level of liver cytochrome P450 2E1 in dosage dependent level.

    CONCLUSION: Coconut water vinegar has helped to attenuate acetaminophen-induced liver damage by restoring antioxidant activity and suppression of inflammation.

    Matched MeSH terms: Acetaminophen/toxicity*
  15. Uthaya Kumar US, Chen Y, Kanwar JR, Sasidharan S
    Oxid Med Cell Longev, 2016;2016:6841348.
    PMID: 28053693 DOI: 10.1155/2016/6841348
    The therapeutic potential of Cassia surattensis in reducing free radical-induced oxidative stress and inflammation particularly in hepatic diseases was evaluated in this study. The polyphenol rich C. surattensis seed extract showed good in vitro antioxidant. C. surattensis seed extract contained total phenolic content of 100.99 mg GAE/g dry weight and there was a positive correlation (r > 0.9) between total phenolic content and the antioxidant activities of the seed extract. C. surattensis seed extract significantly (p < 0.05) reduced the elevated levels of serum liver enzymes (ALT, AST, and ALP) and relative liver weight in paracetamol-induced liver hepatotoxicity in mice. Moreover, the extract significantly (p < 0.05) enhanced the antioxidant enzymes and glutathione (GSH) contents in the liver tissues, which led to decrease of malondialdehyde (MDA) level. The histopathological examination showed the liver protective effect of C. surattensis seed extract against paracetamol-induced histoarchitectural alterations by maximum recovery in the histoarchitecture of the liver tissue. Furthermore, histopathological observations correspondingly supported the biochemical assay outcome, that is, the significant reduction in elevated levels of serum liver enzymes. In conclusion, C. surattensis seed extract enhanced the in vivo antioxidant status and showed antihepatotoxic activities, which is probably due to the presence of phenolic compounds.
    Matched MeSH terms: Acetaminophen/toxicity*
  16. Lim AY, Segarra I, Chakravarthi S, Akram S, Judson JP
    BMC Pharmacol., 2010;10:14.
    PMID: 20950441 DOI: 10.1186/1471-2210-10-14
    BACKGROUND: Sunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D). Paracetamol was administered 15 min before sunitinib. Mice were sacrificed 4 h post sunitinib administration.
    RESULTS: Group-A serum ALT and AST levels were 14.29 ± 2.31 U/L and 160.37 ± 24.74 U/L respectively and increased to 249.6 ± 222.7 U/L and 377.1 ± 173.6 U/L respectively in group-B; group-C ALT and AST ranged 36.75-75.02 U/L and 204.4-290.3 U/L respectively. After paracetamol coadministration with low sunitinib doses (group-D), ALT and AST concentrations ranged 182.79-221.03 U/L and 259.7-264.4 U/L respectively, lower than group-B. Paracetamol coadministration with high sunitinib doses showed higher ALT and AST values (range 269.6-349.2 U/L and 430.2-540.3 U/L respectively), p < 0.05. Hepatic histopathology showed vascular congestion in group-B; mild congestion in group-C (but lesser than in group-B and D). In group-D, at low doses of sunitinib, lesser damage than in group-B occurred but larger changes including congestion were observed at high sunitinib doses. BUN levels were higher (p < 0.05) for group-B (33.81 ± 5.68 mg/dL) and group-D (range 35.01 ± 6.95 U/L to 52.85 ± 12.53 U/L) compared to group-A (15.60 ± 2.17 mg/dL) and group-C (range 17.50 ± 1.25 U/L to 26.68 ± 6.05 U/L). Creatinine remained unchanged. Renal congestion and necrosis was lower in group-C than group-B but was higher in group-D (p > 0.05). Mild cardiotoxicity occurred in groups B, C and D. Brain vascular congestion occurred at high doses of sunitinib administered alone or with paracetamol. Hepatic and renal biomarkers correlated with histopathology signs.
    CONCLUSIONS: Paracetamol and sunitinib coadministration may lead to dose dependent outcomes exhibiting mild hepatoprotective effect or increased hepatotoxicity. Sunitinib at high doses show renal, cardiac and brain toxicity. Liver and renal function monitoring is recommended.
    Matched MeSH terms: Acetaminophen/toxicity*
  17. Fakurazi S, Hairuszah I, Nanthini U
    Food Chem Toxicol, 2008 Aug;46(8):2611-5.
    PMID: 18514995 DOI: 10.1016/j.fct.2008.04.018
    Initiation of acetaminophen (APAP) toxicities is believed to be promoted by oxidative stress during the event of overdosage. The aim of the present study was to evaluate the hepatoprotective action of Moringa oleifera Lam (MO), an Asian plant of high medicinal value, against a single high dose of APAP. Groups of five male Sprague-Dawley rats were pre-administered with MO (200 and 800 mg/kg) prior to a single dose of APAP (3g/kg body weight; p.o). Silymarin was used as an established hepatoprotective drug against APAP induced liver injury. The hepatoprotective activity of MO extract was observed following significant histopathological analysis and reduction of the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in groups pretreated with MO compared to those treated with APAP alone. Meanwhile, the level of glutathione (GSH) was found to be restored in MO-treated animals compared to the groups treated with APAP alone. These observations were comparable to the group pretreated with silymarin prior to APAP administration. Group that was treated with APAP alone exhibited high level of transaminases and ALP activities besides reduction in the GSH level. The histological hepatocellular deterioration was also evidenced. The results from the present study suggested that the leaves of MO can prevent hepatic injuries from APAP induced through preventing the decline of glutathione level.
    Matched MeSH terms: Acetaminophen/toxicity*
  18. Mahmood ND, Mamat SS, Kamisan FH, Yahya F, Kamarolzaman MF, Nasir N, et al.
    Biomed Res Int, 2014;2014:695678.
    PMID: 24868543 DOI: 10.1155/2014/695678
    Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups (n=6) and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of hepatic structure was observed in group pretreated with N-acetylcysteine and MEMC. Hepatotoxic rats pretreated with NAC or MEMC exhibited significant decrease (P<0.05) in ALT and AST enzymes level. Moreover, the extract also exhibited good antioxidant activity. In conclusion, MEMC exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and, thus warrants further investigations.
    Matched MeSH terms: Acetaminophen/toxicity*
  19. Srivastava N, Mishra S, Iqbal H, Chanda D, Shanker K
    J Ethnopharmacol, 2021 May 10;271:113911.
    PMID: 33571614 DOI: 10.1016/j.jep.2021.113911
    ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga L. rhizome (KGR) is part of more than sixty-one Ayurvedic formulations and commonly known as 'Chandramula'. KGR is widely used in traditional Indian medicines to treat fever (jwar), rheumatism (Amavata), respiratory (Shwasa), hypertension (Vyanabala vaishamya) and cardiovascular disorders (Vyanavayu Dushtijanya Hrudrog). Although ethnomedicinal properties have extensively been demonstrated in traditional medicines of south-east countries i.e. China, India, Indonesia, and Malaysia, the chemico-biological validation are still lacking.

    AIM OF THE STUDY: Chemico-biological standardization with respect to its vasorelaxation potential is the main objective of the present study. To investigate the vasorelaxation potential of key phytochemical of KGR, i.e., ethyl-p-methoxycinnamate (EPMC) and to study it's the mechanism of action.

    MATERIALS AND METHODS: A HPLC method was developed and validated for the quality assessment of KGR using its two major phytochemicals i.e. ethyl-p-methoxycinnamate (EPMC) and ethyl cinnamate (EC) in KGR. The vasorelaxation effect of major phytochemicals of KGR was evaluated on the main mesenteric arteries isolated from male Wistar rats. Specific BKca channel blocker tetraethylammonium (TEA), receptor antagonist, nitric oxide scavenging capacity, and antioxidant potential were also evaluated for its plausible mechanism.

    RESULTS: Present validated HPLC method facilitates simultaneous quantitation of EPMC and EC faster than classical GC techniques. EPMC has shown a dose-dependent relaxation in rat main mesenteric arteries (MMA) contracted by U46619 with an Emax of 58.68 ± 3.31%. Similarly, in endothelium-denuded MMA rings, relaxation was also observed (Emax of 61.83 ± 3.38%). Moreover, relaxation response to EPMC has strongly inhibited (Emax 14.76 ± 2.29%) when the tissue exposed to depolarizing high K+ containing buffer for the contraction. The point correlation dimension (pD2) values were also significantly decreased in high K+ treated arterial rings compared to control. Interestingly, when MMA rings incubated with a specific BKca channel blocker (TEA, 1 mM), the relaxation response to EPMC was also significantly blocked.

    CONCLUSIONS: The first time this study demonstrated the chemical standardization of K. galanga rhizome and EPMC is responsible for its vasorelaxation potential as demonstrated by the endothelium-independent response mediated by Ca2+ dependent potassium channels.

    Matched MeSH terms: Acetaminophen/toxicity
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