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1.
BMC Nephrol ; 21(1): 38, 2020 01 31.
Article in English | MEDLINE | ID: mdl-32005171

ABSTRACT

BACKGROUND: Chronic Kidney Disease of unknown etiology (CKDu) is prevalent in North Central Province (NCP) of Sri Lanka. Consumption of un-boiled dug well water has been identified as one of the causative factors. This in-vivo study was performed to investigate some of the suspected factors associated with the pathogenesis of CKDu mediated via ground water. METHOD: Rats were given water, collected from high and low disease prevalent areas from the NCP of Sri Lanka and the results compared with those obtained from previously identified low disease prevalent area; Colombo. Blood Urea Nitrogen, creatinine, urinary microalbumin:creatinine ratio together with ALT and AST levels were analyzed and results were compared using one-way ANOVA and paired t-Test. Histopathology was analyzed using non-parametric method. RESULTS: Rats that ingested water from New Town Medirigiriya (NTM) from high disease prevalent NCP reported significantly elevated microalbumin:creatinine ratios compared to other water sources after 8 months, whilst boiled water from NTM had been able to significantly reduce it. Histopathological findings after the 14 months experimental period revealed significantly high tubular lesion index in rats that ingested water from NCP compared to Colombo. Rats that ingested water from high disease prevalent Divuldamana (DD) from NCP showed the highest kidney lesion index though the fluoride content was relatively low in this area compared to other water sources from high disease prevalent NCP. Rats that ingested boiled and un-boiled water from NTM also developed severe lesions whilst the group from Colombo reported the lowest. Low disease prevalent area from NCP, Huruluwewa (HW) also reported elevated liver enzymes and altered renal histopathology. Association of Na+:Ca2+ ratio in the disease progression was not reflected by the current study. Compared to Colombo, high fluoride, calcium and sodium contents were observed in water from high disease prevalent areas. All the water samples were negative for heavy metals. CONCLUSIONS: Though Fluoride is a known kidney toxic agent it cannot be the sole reason for CKDu in NCP, Sri Lanka. Various toxic elements present in NCP water may contribute to different grade of kidney and liver lesions in Wistar rats.


Subject(s)
Drinking Water/adverse effects , Drinking Water/chemistry , Groundwater/chemistry , Renal Insufficiency, Chronic/etiology , Alanine Transaminase/blood , Albuminuria/urine , Animals , Aspartate Aminotransferases/blood , Blood Urea Nitrogen , Calcium/analysis , Creatinine/blood , Creatinine/urine , Drinking Water/administration & dosage , Female , Fluorides/analysis , Hepatitis/blood , Hepatitis/etiology , Hepatitis/pathology , Kidney Tubules/pathology , Male , Random Allocation , Rats , Rats, Wistar , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/pathology , Renal Insufficiency, Chronic/urine , Sodium/analysis , Sri Lanka
2.
Pharmacogn Mag ; 6(23): 186-90, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20931077

ABSTRACT

Aqueous extracts of mature leaves of Artocarpus heterophyllus (jak) are used by traditional medical practitioners in Sri Lanka and India for the treatment of diabetes. This study was conducted to investigate the hypoglycemic and hypolipidemic effects of an ethylacetate (EA) fraction of the mature leaves of A. heterophyllus in a streptozotocin (STZ) induced diabetic rat model. In normoglycemic rats, administration of a single dose (20 mg/kg) of the EA fraction resulted in a significant (P < 0.05) reduction in the fasting blood glucose concentration and a significant improvement in glucose tolerance (P < 0.05), compared to the controls. In STZ-induced diabetic rats, chronic administration of the EA fraction of A. heterophyllus leaves daily for 5 weeks resulted in a significant lowering of serum glucose, cholesterol and triglyceride (TG) levels. Compared to control diabetic rats, the extract-treated rats had 39% less serum glucose, 23% lower serum total cholesterol and 40% lower serum TG levels and 11% higher body weight at the end of the fifth week. The percentage reductions in the serum parameters mediated by the test fraction were comparable with those produced by glibenclamide (0.6 mg/kg), the reference drug used in this study. It can be concluded that the EA fraction of A. heterophyllus leaves contains one or more hypoglycemic and hypolipidemic principles which have the potential to be developed further for the treatment of diabetes specifically associated with a hyperlipidemic state.

3.
J Ethnopharmacol ; 127(3): 750-4, 2010 Feb 17.
Article in English | MEDLINE | ID: mdl-19963056

ABSTRACT

AIM OF THE STUDY: The aim of the present study was to scientifically investigate whether Trichosanthes cucumerina Linn (Family: Cucurbitaceae) has gastroprotective activity. MATERIALS AND METHODS: All the experiments were conducted using Wistar strain rats (weight: 200-220 g). The food and water given to rats was withdrawn for 36 and 12h respectively, before the commencement of the experiment. These rats were randomly divided into 6 groups (n=8 rats/group; 4 males+4 females) and groups 1-3 were orally administrated with hot water extract (HWE) at a dose of 375, 500 and 750 mg/kg, respectively. Group 4 was orally treated with equal volume of distilled water (1 mL; control), group 5 was orally treated with a reference drug, cimetidine (100mg/kg) while the group 6 was orally treated with another reference drug, sucralfate (400mg/kg). In the indomethacin experiment, only one dose of HWE (750 mg/kg) was tested, as this was found to have the maximum effect in the alcohol model also. RESULTS: Results show that the HWE of Trichosanthes cucumerina possesses significant (P

Subject(s)
Anti-Ulcer Agents/therapeutic use , Gastric Mucosa/drug effects , Histamine Antagonists/pharmacology , Plant Extracts/therapeutic use , Stomach Ulcer/drug therapy , Trichosanthes/chemistry , Animals , Anti-Ulcer Agents/pharmacology , Cimetidine/pharmacology , Disease Models, Animal , Ethanol , Female , Gastric Juice/drug effects , Hydrogen-Ion Concentration , Indomethacin , Male , Mucus/metabolism , Plant Components, Aerial , Plant Extracts/pharmacology , Random Allocation , Rats , Rats, Wistar , Stomach Ulcer/chemically induced , Sucralfate/pharmacology
4.
J Carcinog ; 5: 11, 2006 May 09.
Article in English | MEDLINE | ID: mdl-16684351

ABSTRACT

BACKGROUND: A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root bark and Smilax glabra rhizome is being recommended for cancer patients by a family of traditional medical practitioners of Sri Lanka. Previous investigations have demonstrated that a short term (10 weeks) treatment with the decoction can significantly inhibit diethylnitrosamine (DEN) mediated expression of Glutathione S-transferase P form (GST-P) in rat liver. The objective of the present investigation was to determine whether long term (16 months) treatment with the decoction would be successful in inhibiting in rat livers, not only DEN- mediated expression of GST-P, but also the carcinogen mediated development of overt tumours (OT) or histopathological changes leading to tumour development (HT). METHODS: Thirty-six male Wistar rats were divided into 3 groups of 12 each. Groups 1 and 2 were injected intraperitoneally (i.p) with DEN (200 mg/kg) while group 3 was injected normal saline (NS). Twenty-four hours later, decoction (DC; 6 g/kg body weight/day) was orally administered to group 1 rats, while groups 2 and 3 (DEN-control and normal control) were given distilled water (DW). Treatment with DC or DW continued for 16 months. At the end of the 9th month and 16th months (study 1 and study 2 respectively), six rats from each group were sacrificed, and livers observed for OT or HT, both visually and by subjecting liver sections to staining with Haemotoxylin and Eosin (H & E), Sweet's Silver stain (for reticulin fibers), Periodic Acid Schiff (PAS) staining (for glycogen), and immunohistochemical staining (for GST-P). RESULTS: At the end of 9 months (study 1) a hepatocellular adenoma (HA) developed in one of the rats in the DEN + DW treated group (group 2). At the end of 16 months (study 2), livers of all rats of group 2 developed OT and HT. Large areas of GST-P positive foci were also observed. No OT, HT or GST-P positive foci were detected in any of the other groups. CONCLUSION: Protection against DEN-mediated carcinogenic changes in rat liver can be achieved by long term treatment with the DC comprised of N. sativa seeds, S. glabra rhizome and H. indicus root bark.

5.
Drug Metabol Drug Interact ; 20(4): 263-72, 2004.
Article in English | MEDLINE | ID: mdl-15663295

ABSTRACT

The effects of concurrent administration of herbal tea prepared from dried flowers of Cassia auriculata or aerial parts of Cardospermum halicacabum and steady state serum levels of theophylline was investigated in Wistar rats. Results obtained demonstrate that a significant increase in the steady state levels of theophylline occur when this drug is administered concurrently with herbal tea prepared from either of the above plants. C. auriculata and C. halicacabum enhanced the steady state levels of theophylline by 32.5% (p < 0.02) and 48.2% (p < 0.02), respectively, when compared with the levels in animals receiving theophylline alone for the same time period. Herbal teas prepared from C. auriculata or C. halicacabum should therefore be avoided by patients treated with theophylline as these herbal teas have the potential to influence the bioavailability of the prescription drug.


Subject(s)
Beverages , Cassia , Herb-Drug Interactions , Plant Preparations/pharmacology , Theophylline/blood , Animals , Biological Availability , Bronchodilator Agents/blood , Chromatography, High Pressure Liquid/methods , Male , Rats , Rats, Wistar , Sapindaceae
6.
J Ethnopharmacol ; 84(1): 47-50, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12499076

ABSTRACT

Liv.52, a hepatoprotective agent of herbal origin, is used empirically for the treatment of alcoholic liver disease in Sri Lanka. We conducted a controlled trial to assess the efficacy of Liv.52 in patients with alcoholic liver disease. Patients with evidence of alcoholic liver disease attending outpatient clinics were included in a prospective, double blind, randomized, placebo controlled trial. During the trial period, 80 patients who fulfilled inclusion criteria were randomly assigned Liv.52 (cases; n = 40) or placebo (controls) the recommended dose of three capsules twice daily for 6 months. All patients underwent clinical examination (for which a clinical score was computed), and laboratory investigations for routine blood chemistry and liver function before commencement of therapy (baseline). Thereafter, clinical assessments were done monthly for 6 months, while laboratory investigations were done after 1 and 6 months of therapy. There was no significant difference in the age composition, alcohol intake and baseline liver function between the two groups. The two-sample t-test was used to analyze data obtained after 1 and 6 months of therapy against baseline values. There was no significant difference in clinical outcome and liver chemistry between the two groups at any time point. There were no reports of adverse effects attributable to the drug. Our results suggest that Liv.52 may not be useful in the management of patients with alcohol induced liver disease.


Subject(s)
Liver Diseases, Alcoholic/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Plants, Medicinal , Adult , Aged , Alcoholism/complications , Drug Combinations , Female , Humans , Liver Diseases, Alcoholic/complications , Liver Diseases, Alcoholic/physiopathology , Liver Function Tests , Male , Middle Aged , Plant Extracts/adverse effects , Random Allocation , Treatment Outcome
7.
Phytother Res ; 15(6): 519-23, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11536382

ABSTRACT

Reactive oxygen species (ROS) are implicated in many pathogenic processes including the cardiovascular system. Detoxification of ROS by antioxidants (AO) therefore affords protection against such diseases. There is a growing body of evidence suggesting that antioxidants contribute to cardioprotection. Therefore, nine plants that are components of Ayurvedic formulations used for the therapy of cardiovascular diseases were investigated to determine whether antioxidant activity is one of the mechanisms by which these plants exert cardioprotection. Initially aqueous freeze dried extracts of the plants were prepared and the antioxidant activity was measured (a) in vitro, by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging and deoxyribose damage protection assays, and (b) in vivo, by effects on lipid peroxidation. Terminalia arjuna showed significant DPPH radical scavenging activity with EC(50) 8.3 +/- 0.3 microg/mL (similar to L-ascorbic acid). The potency of this activity was much lower in Cassia fistula (EC(50) = 59.0 +/- 2.7 microg/mL). The other seven extracts demonstrated no such activity in the concentration range tested. In the deoxyribose damage protection assay, T. arjuna> demonstrated no significant effect in the concentration range 0-20 microg/mL, but above -20 microg/mL concentration (20-125 microg/mL), a pro-oxidant activity was observed (although markedly less than demonstrated by L-ascorbic acid). A similar trend was observed with Vitex negundo. In contrast, C. fistula afforded a 30% protection against such damage at 125 microg/mL concentration. Other plant extracts did not show any activity in this assay. At a dose of 90 mg/kg (single dose) T. arjuna, cardiac lipid peroxidation in male Wistar rats was reduced by 38.8% +/- 2.6% (p<0.05) whereas the reduction was only 11.6% +/- 3.5% in the case of C. fistula even at a dose of 120 mg/kg. Of all the plants tested, T. arjuna demonstrated the highest antioxidant activity. Overall results show that only some plants used in the therapy of cardiovascular disease exert their beneficial effects via antioxidant activity.


Subject(s)
Antioxidants/pharmacology , Bepridil/analogs & derivatives , Cardiotonic Agents/pharmacology , Cardiovascular Diseases/prevention & control , Lipid Peroxidation/drug effects , Magnoliopsida , Medicine, Ayurvedic , Phytotherapy , Picrates , Plant Extracts/pharmacology , Animals , Antioxidants/therapeutic use , Bepridil/metabolism , Biphenyl Compounds , Cardiotonic Agents/therapeutic use , Deoxyribose/metabolism , Free Radical Scavengers/pharmacology , Free Radicals/metabolism , Herbal Medicine , Male , Plant Extracts/therapeutic use , Plants, Medicinal , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Sri Lanka , Thiobarbituric Acid Reactive Substances/metabolism
8.
J Ethnopharmacol ; 76(3): 285-91, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11448551

ABSTRACT

Reactive oxygen intermediates (ROI) are together with prostanoids, leukotrienes and proteases, believed to be the mediators of inflammation and responsible for the pathogenesis of tissue destruction in RA. Antioxidant (AO) activity is one of the mechanisms by which many conventional drugs used in day to day treatment of RA alleviate the painful symptoms associated with this disease. An investigation has been carried out to compare the antioxidant potentials of two polyherbal formulations, Maharasnadhi quathar (MRQ) and Weldehi choornaya (WC), used by Ayurvedic medical practitioners in Sri-Lanka for the treatment of RA patients. AO potentials of these preparations were assessed by their effects in RA patients on: (a) activities of the AO enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase; (b) lipid peroxidation (as estimated by thiobarbituric acid reacting substances (TBARS) generation); and (c) concentrations of serum iron and haemoglobin (Hb), and the total iron binding capacity (TIBC). The overall results of the study demonstrate that MRQ has much greater AO potential than WC. Thus, on treatment with MRQ for 3 months, the initial activities of plasma SOD, GPX and catalase, were enhanced by 44.6, 39.8 and 25.2%, respectively. There was no significant improvement in any of these enzyme activities in patients treated with WC for the same time period as MRQ. Although the extent of lipid peroxidation in plasma of RA patients could be decreased by both drug preparations, the reduction mediated in 3 months by MRQ (34%) was markedly greater than that due to WC (21.8%). The total serum iron and Hb concentrations and TIBC in the RA patients included in the study could be significantly improved by treatment with MRQ but not by WC. Thus, at the end of 3 months treatment with MRQ, concentrations of the total serum iron and Hb, and the TIBC of patients improved by 26.8, 24.8 and 16.1%, respectively. Possible reasons for differences in the AO potentials of MRQ and WC are discussed.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/pharmacology , Arthritis, Rheumatoid/drug therapy , Medicine, Ayurvedic , Phytotherapy , Plant Extracts/therapeutic use , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Catalase/blood , Catalase/drug effects , Drug Therapy, Combination , Female , Glutathione Peroxidase/blood , Glutathione Peroxidase/drug effects , Hemoglobins/analysis , Humans , Iron/metabolism , Lipid Peroxidation/drug effects , Middle Aged , Plant Extracts/blood , Plant Extracts/pharmacology , Plants, Medicinal , Sri Lanka , Superoxide Dismutase/blood , Superoxide Dismutase/drug effects
9.
Phytother Res ; 14(3): 215-7, 2000 May.
Article in English | MEDLINE | ID: mdl-10815020

ABSTRACT

The effects of oral garlic supplementation on the activities of (a) the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) and (b) lipid peroxidation, as assessed by malondialdehyde (MDA) production in red blood cells of normal mice and those subject to oxidative stress by chronic administration of the anti-tumour drug adriamycin has been investigated. As expected, adria-mycin administration resulted in a significant increase in MDA generation (by 105.4%) and a decrease in GPX activity (by 23.8%) in the red blood cells. Although garlic had no significant effects on the basal levels of the antioxidant enzymes or MDA generation in red blood cells of normal mice (untreated with adriamycin), at doses of 20 mg/kg or 100 mg/kg, garlic was able to decrease significantly the adriamycin induced changes in the oxido-reductive status of the red blood cells. Thus, on administration of adriamycin to mice fed diets containing 20 mg/kg or 100 mg/kg garlic, the drug-induced increase in MDA generation was 38.2% and 22.5% respectively, less than that produced by adriamycin in mice fed normal diets, containing no garlic (105.4%). Similarly, in mice fed diets providing 20 mg/kg and 100 mg/kg garlic, adriamycin was able to decrease GPX activity by only 15.1% and 7.6% respectively, less than that produced by adriamycin in rats fed normal diets, containing no garlic (23.9%).


Subject(s)
Doxorubicin/toxicity , Erythrocytes/metabolism , Garlic/therapeutic use , Phytotherapy , Plants, Medicinal , Animals , Dietary Supplements , Erythrocytes/drug effects , Glutathione Peroxidase/blood , Lipid Peroxidation/drug effects , Male , Malondialdehyde/blood , Mice , Oxidation-Reduction , Rats , Superoxide Dismutase/blood
10.
J Pharm Pharmacol ; 52(4): 461-5, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10813559

ABSTRACT

Previous investigations have confirmed the protective effect of Osbeckia aspera leaf extract on carbon tetrachloride-mediated liver injury in rat models. It is well known that the earliest alterations in liver cell structure and function following carbon tetrachloride poisoning involve the endoplasmic reticulum and its drug metabolizing enzymes. Therefore, we investigated whether an aqueous leaf extract of O. aspera could offer protection against carbon tetrachloride-induced changes in the microsomal drug metabolizing enzymes aniline hydroxylase and p-aminopyrine N-demethylase. This enzyme activity was compared with phenobarbital-induced righting reflex and lipid peroxidation. Treatment of rats with the aqueous leaf extract of O. aspera (before or after the administration of carbon tetrachloride) resulted in a marked decrease in carbon tetrachloride-mediated alterations in aniline hydroxylase and p-aminopyrine N-demethylase activity, phenobarbital-induced loss of righting reflex and malondialdehyde formation due to lipid peroxidation. The Km value of these enzymes in control and Osbeckia-treated rats were the same. These results show that the plant extract can markedly decrease the carbon tetrachloride-mediated reduction in aniline hydroxylase and p-aminopyrine N-demethylase activity and inhibit peroxidative damage to the cell membrane. Phenobarbital-induced sleeping time in rats and kinetic enzyme studies suggested that the effects of the plant extract was neither due to an induction of the drug-metabolizing enzymes under investigation, nor due to an alteration in the Km values of these enzymes.


Subject(s)
Carbon Tetrachloride/administration & dosage , Microsomes, Liver/drug effects , Plant Extracts/pharmacology , Aminopyrine N-Demethylase/drug effects , Aminopyrine N-Demethylase/metabolism , Aniline Hydroxylase/drug effects , Aniline Hydroxylase/metabolism , Animals , Dose-Response Relationship, Drug , Kinetics , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Malondialdehyde/metabolism , Medicine, Traditional , Microsomes, Liver/enzymology , Plant Extracts/chemistry , Plant Leaves/chemistry , Rats , Rats, Wistar , Reflex/drug effects
11.
Ceylon Med J ; 45(3): 119-22, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11192991

ABSTRACT

OBJECTIVE: To identify possible gender related differences in performance at undergraduate medical examinations in Sri Lanka. STUDY DESIGN AND METHODS: Results of examinations conducted by the faculty of medicine, University of Kelaniya in 1997 and 1998, and data published by the University Grants Commission (UGC) on final examinations conducted by 4 other Sri Lankan medical faculties (in the Universities of Colombo, Peradeniya, Ruhuna and Jaffna) in 1996 and 1997, were analysed for sex related differences. RESULTS: The proportion of women in each batch of students who sat for 8 examinations conducted at the faculty of medicine, University of Kelaniya in 1997 and 1998, ranged from 40.7 to 48.4% (average 44.3%). Among students sitting for the final MBBS examinations in other medical faculties in 1996 and 1997, the proportion of women ranged from 37.3% in Peradeniya to 53.7% in Jaffna. The proportions of women who obtained "classes" were higher than that of men in 12/15 examinations, with statistically significant differences in four. Higher proportions of men were referred or failed in all 8 examinations analysed; the differences were statistically significant in two. CONCLUSIONS: Women appear to do marginally better than men in undergraduate medical examinations in Sri Lanka.


Subject(s)
College Admission Test , Students, Premedical , Adult , Female , Humans , Male , Sex Factors , Sri Lanka
12.
Ann Clin Biochem ; 36 ( Pt 2): 216-20, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10370740

ABSTRACT

The effect of oral vitamin E supplementation on the oxido-reductive status of red blood cells in normal mice and those subject to oxidative stress by chronic administration of the anti-tumour drug Adriamycin was investigated. Mice were randomly separated into three groups of 20 animals each and maintained on diets identical in all respects except for vitamin E content. Group 1 received a low vitamin E diet that provided 10 mg vitamin E/kg body weight/day, group 2 received a normal mice chow diet (45 mg vitamin E/kg body weight/day) while group 3 received a high vitamin E diet (200 mg vitamin E/kg body weight/day). In comparison with the normal mice in group 1, their counterparts in groups 2 and 3 exhibited significantly higher (P < 0.001) activities of superoxide dismutase (SOD) in red blood cells (79.4% higher in group 2 and 114.2% higher in group 3, respectively) and produced lower concentrations of malondialdehyde (MDA) (22.9% less in group 2 and 51.2% less in group 3, respectively), with little difference in the glutathione peroxidase (GPX) activity. In Adriamycin-treated animals on the low vitamin E diet (group 1) the red blood cell SOD activity and MDA production were 46.2% and 200.7% higher (P < 0.001), respectively, and the GPX activity was 39.1% lower than in the red blood cells of untreated (normal) animals in the same group. The Adriamycin-induced changes were significantly less in animals receiving higher doses of vitamin E (groups 2 and 3). Thus, in the group maintained on the high vitamin E diet (group 3), Adriamycin administration resulted in only a 38.9% increase in the MDA production above that generated by red blood cells of normal mice in the same group, with no significant change in the SOD or GPX activities. Thus, in normal conditions as well as in conditions of oxidative stress, high doses of vitamin E appear to be able to protect the oxido-reductive status of red blood cells by modulating the extent of lipid peroxidation as well as the activities of antioxidant enzymes.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Doxorubicin/adverse effects , Erythrocytes/metabolism , Vitamin E/pharmacology , Administration, Oral , Animals , Erythrocytes/drug effects , Glutathione Peroxidase/metabolism , Lipid Peroxidation/drug effects , Male , Malondialdehyde/metabolism , Mice , Oxidation-Reduction/drug effects , Oxidative Stress , Superoxide Dismutase/metabolism , Vitamin E/administration & dosage
13.
Int J Artif Organs ; 22(2): 113-7, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10212046

ABSTRACT

Patients with acute liver failure accumulate toxic substances in the circulation which may impair recovery of hepatic function. The aim of this study was to test an in vitro assay to detect inhibitory substances in the serum of patients with acute liver failure. Human liver-derived HepG2 cells were incubated for 24h in 96 well plates (30,000 cells/well) with sera (10%) from 24 patients with acute liver failure due to paracetamol overdose or NANB hepatitis and 11 normal controls. DNA synthesis was determined from the incorporation of 3H-thymidine and cell viability by the metabolism of the tetrazolium dye MTS. HepG2 cells exposed to acute liver failure sera incorporated significantly less 3H-thymidine (median 30% of control, range 0.2-169%) than normal sera (100%, 76-133%, p=0.002). Cell viability was also reduced (75%, 33-112% vs 100%, 96-105%, p<0.001). There was no correlation between these values and patient outcome or levels of plasma TNF-alpha or serum interferon-gamma. The assay detected inhibitory substances in sera of patients with acute liver failure and could be used to monitor the use of liver support systems.


Subject(s)
Hepatic Encephalopathy/blood , Acetaminophen/poisoning , Adolescent , Adult , Analgesics, Non-Narcotic/poisoning , Cell Survival , Cells, Cultured , DNA/biosynthesis , Enzyme-Linked Immunosorbent Assay , Female , Hepatic Encephalopathy/etiology , Hepatitis, Viral, Human/complications , Humans , Interferon-gamma/blood , Male , Middle Aged , Statistics, Nonparametric , Tumor Necrosis Factor-alpha/analysis
14.
J Pharm Pharmacol ; 49(11): 1132-5, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9401951

ABSTRACT

Identification of the active components of plants with hepatoprotective properties requires screening of large numbers of samples during fractionation and purification. A screening assay has been developed based on protection of human liver-derived HepG2 cells against toxic damage. Various hepatotoxins were incubated with HepG2 cells in 96-well microtitre plates (30,000 cells well-1) for 1 h and viability was determined by metabolism of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS). Bromobenzene (10 mM) and 2,6-dimethyl-N-acetyl-p-quinoneimine (2,6-diMeNAPQI, 200 mM) had greater toxic effects than tert-butyl hydroperoxide (1.8 mM) or galactosamine (10 mM), reducing mean viability to 44.6 +/- 1.2% (s.e.m.) and 56.1 +/- 2.1% of control, respectively. Protection against toxic damage by these agents was tested using a crude extract of a known hepatoprotective Sri Lankan plant, Osbeckia aspera, and two pure established hepatoprotective plant compounds, (+)-catechin and silymarin (1 mg mL-1). Viability was significantly improved by Osbeckia (by 37.7 +/- 2.4%, P < 0.05, and 36.5 +/- 2.1%, P < 0.05, for bromobenzene and 2,6-diMeNAPQI toxicity, respectively). Comparable values for (+)-catechin were 68.6 +/- 2.9% and 63.5 +/- 1.1%, and for silymarin 24.9 +/- 1.4% and 25.0 +/- 1.6%. This rapid and reproducible assay should prove useful for the isolation and identification of active hepatoprotective compounds in crude plant extracts.


Subject(s)
Bromobenzenes/toxicity , Cell Survival/drug effects , Liver/drug effects , Plant Extracts/therapeutic use , Bromobenzenes/antagonists & inhibitors , Catechin/therapeutic use , Cells, Cultured , Drug Evaluation, Preclinical/methods , Humans , Liver/cytology , Silymarin/therapeutic use , Tetrazolium Salts/metabolism , Thiazoles
15.
J Ethnopharmacol ; 49(2): 69-76, 1995 Dec 01.
Article in English | MEDLINE | ID: mdl-8847886

ABSTRACT

Ayurvedic and other 'traditional' medical practitioners in Sri Lanka use the mature leaves of the plant Osbeckia octandra for its hepatoprotective properties. In this study the effects of an aqueous extract of Osbeckia octandra against injury induced by D-galactosamine and tert-butyl hydroperoxide (TBH) were investigated in freshly isolated rat hepatocytes. The plant extract (500 micrograms/ml) significantly reduced the inhibition of protein synthesis (as assessed by the incorporation of 14C-leucine into protein) in hepatocytes incubated for 1 h with 10 mM galactosamine by a mean of 25.6 +/- 3.6% and decreased the release of cellular lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) enzyme activities into the medium by 55.3% and 32.8%, respectively. With TBH, the plant extract decreased lipid peroxidation (estimated from malondialdehyde formation) by a mean of 29.9 +/- 1.1% together with a 46.8% and 54.7% decrease in the release of LDH and AST, respectively into the incubation medium. Significant protection was also obtained when the Osbeckia extract was added to the incubation medium up to 30 min after pre-exposure of the hepatocytes to either galactosamine or, to a lesser extent, TBH. The results support the use of Osbeckia as a hepatoprotective agent.


Subject(s)
Galactosamine/pharmacology , Hydrogen Peroxide/pharmacology , Liver/drug effects , Plant Extracts/pharmacology , Animals , Dose-Response Relationship, Drug , Male , Medicine, Traditional , Rats , Rats, Wistar , Sri Lanka
16.
Xenobiotica ; 25(9): 1009-17, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8553682

ABSTRACT

1. Osbeckia octandra is a plant used in traditional medicine to treat jaundice and other liver disorders. In this study, the effects of Osbeckia leaf extract on paracetamol-induced liver injury were investigated both in vivo in mice and in rat hepatocytes in vitro. 2. Oral administration of Osbeckia extract (330 mg/kg) at the same time as paracetamol (450 mg/kg) to mice, resulted in a significant protection (p < 0.05) against liver damage, as assessed by improvements in the blood Normotest (39.1 +/- 1.9 versus 46.3 +/- 2.0 s), total liver glutathione (730 +/- 39 versus 574 +/- 27 micrograms/250 mg liver), plasma aspartate aminotransferase level (916 +/- 225 versus 1965 +/- 291 iu/l), and liver histopathology at 24 h after paracetamol administration. 3. In experiments to assess the direct effects of Osbeckia extract, significant protection was also found in freshly isolated rat hepatocytes against damage induced by 185 microM 2,6-dimethyl N-acetyl p-quinoneimine (2,6-diMeNAPQI, an analogue of NAPQI, the toxic metabolite of paracetamol) in vitro. When Osbeckia extract (500 micrograms/ml) was added to the incubation medium at the same time as 2,6-diMeNAPQI significant changes in cell viability (78.4 +/- 3.3 versus 47.2 +/- 5.8% of control, p < 0.001), cell reduced glutathione (GSH) level (35.0 +/- 3.1 versus 23.8 +/- 1.5%, p = 0.009), and reduced release of lactate dehydrogenase (129.9 +/- 6.6 versus 224.6 +/- 12.1%, p < 0.001) were demonstrated after 1 h incubation as compared with 2,6-diMeNAPQI alone. 4. Significant protection was still obtained against 2,6-diMeNAPQI in vitro when addition of Osbeckia extract was delayed by 20 min. These results indicate that Osbeckia extract can protect against paracetamol-induced liver injury.


Subject(s)
Acetaminophen/toxicity , Analgesics, Non-Narcotic/toxicity , Chemical and Drug Induced Liver Injury/prevention & control , Liver/drug effects , Plant Extracts/pharmacology , Plants, Medicinal , Animals , Cells, Cultured , Liver/metabolism , Liver/pathology , Mice , Mice, Inbred C57BL , Rats
17.
J Ethnopharmacol ; 33(1-2): 63-6, 1991.
Article in English | MEDLINE | ID: mdl-1943175

ABSTRACT

The effects of aqueous extracts of Osbeckia octandra whole plant, Melothria maderaspatana whole plant and Phyllanthus debelis leaves on the human immune system were investigated. The extracts showed strong anticomplement effects on both the classical and alternate pathways of the human complement system in vitro. The effects were dose-dependent and most pronounced in the classical complement pathway assay. The extracts also exhibited a direct dose-dependent inhibition of luminol-induced chemiluminescence of human polymorphonuclear leukocytes upon stimulation with zymosan.


Subject(s)
Adjuvants, Immunologic/pharmacology , Liver Diseases/drug therapy , Plants, Medicinal/chemistry , Antibody Formation/drug effects , Complement Pathway, Alternative/drug effects , Complement Pathway, Classical/drug effects , Humans , Immunity, Cellular/drug effects , In Vitro Techniques , Luminescent Measurements , Luminol/pharmacology , Neutrophils/drug effects , Phagocytosis/drug effects , Plant Extracts/pharmacology , Respiration/drug effects , Respiratory Burst/drug effects , Sri Lanka
18.
J Ethnopharmacol ; 31(3): 277-82, 1991 Mar.
Article in English | MEDLINE | ID: mdl-2056756

ABSTRACT

Investigations were carried out to evaluate the effects of hot-water extracts of Artocarpus heterophyllus leaves and Asteracanthus longifolia whole plant material on the glucose tolerance of normal human subjects and maturity-onset diabetic patients. The extracts of both Artocarpus heterophyllus and Asteracanthus longifolia significantly improved glucose tolerance in the normal subjects and the diabetic patients when investigated at oral doses equivalent to 20 g/kg of starting material.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Glucose Tolerance Test , Hypoglycemic Agents , Plant Extracts/pharmacology , Plants, Medicinal/analysis , Adult , Blood Glucose/metabolism , Humans , Male , Middle Aged , Sri Lanka
19.
J Ethnopharmacol ; 30(1): 97-105, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2214827

ABSTRACT

Treatment with an aqueous extract of the aerial parts of Melothria maderaspatana, before or after CCl4 administration in rats markedly decreased CCl4-mediated reductions in aniline hydroxylase and p-aminopyrine N-demethylase activities. Phenobarbital-induced sleeping time in rats and kinetic enzyme studies showed that the effect of the plant was neither due to an induction of the drug metabolizing enzymes nor due to an alteration in the Km values of the enzymes.


Subject(s)
Carbon Tetrachloride/toxicity , Microsomes, Liver/enzymology , Mixed Function Oxygenases/metabolism , Pharmaceutical Preparations/metabolism , Plant Extracts/pharmacology , Aminopyrine N-Demethylase/metabolism , Aniline Hydroxylase/metabolism , Animals , Chemical and Drug Induced Liver Injury/pathology , Glutathione/blood , Glutathione/metabolism , In Vitro Techniques , Kinetics , Lipid Peroxidation/drug effects , Liver/pathology , Male , Malondialdehyde/metabolism , Microsomes, Liver/drug effects , Phenobarbital/pharmacology , Rats , Rats, Inbred Strains , Sleep/drug effects
20.
Gen Pharmacol ; 21(5): 779-82, 1990.
Article in English | MEDLINE | ID: mdl-2276596

ABSTRACT

1. Investigations were carried out to determine whether aqueous extracts of Osbeckia octandra, Artocarpus heterophyllus and Bambusa vulgaris truly possess oral hypoglycaemic activity. 2. All three plant extracts significantly lowered the fasting blood glucose level and markedly improved glucose tolerance in Sprague-Dawley rats. 3. A maximum hypoglycaemic activity was observed at +3 hr with O. octandra and B. vulgaris; with A. heterophyllus a maximum effect was not observed even at +5 hr. 4. The hypoglycaemic activity of O. octandra was comparable with that of tolbutamide while that of A. heterophyllus or B. vulgaris was better than that of tolbutamide. 5. The magnitude of the hypoglycaemic effects varied with the dosage used and the time of storage (except with A. heterophyllus, whose activity did not change with storage even up to 3 days).


Subject(s)
Hypoglycemic Agents , Plants, Medicinal/analysis , Animals , Blood Glucose/metabolism , Dose-Response Relationship, Drug , Glucose Tolerance Test , Male , Plant Extracts/pharmacology , Rats , Rats, Inbred Strains , Sri Lanka , Tolbutamide/pharmacology
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