Displaying publications 81 - 100 of 205 in total

Abstract:
Sort:
  1. Koriem KM, Arbid MS, El-Gendy NF
    Toxicol. Mech. Methods, 2010 Nov;20(9):579-86.
    PMID: 20883155 DOI: 10.3109/15376516.2010.518171
    The protective role of Tropaelum majus (T.majus) methyl alcohol extract and vitamin E in the case of toxic effect induced by diethyl maleate was evaluated. Forty-two male albino rats were divided into seven groups of six rats each for 15 days. Group 1: normal control group. Group 2: taken daily oral dose of paraffin oil (0.25ml/100g b.wt rat). Group 3: received daily oral dose of vitamin E (100mg/kg b.wt rat). Group 4: taken daily oral dose of 10% of the LD50 of T.majus methyl alcohol extract. Groups 5–7: injected intra-peritoneally with diethyl maleate (5 μl/100g b.wt rat) but groups 6 and 7 received a daily oral dose of either vitamin E or 10% of the LD50 of T.majus methyl alcohol extract 1h prior to diethyl maleate injection. The present results revealed that diethyl maleate induced serum aspartate and alanine aminotransferases enzymes activities decreased in serum, but their activities in the hepatic tissue showed an increase. Glutathione and glucose-6-phosphate dehydrogenase levels showed a decrease, but thiobarbituric acid reactive substances level showed an increase in both serum and liver tissue. Serum and liver proteins decreased in serum and liver tissue. A significant decrease in blood parameters (hemoglobin, hematocrit, as well as red and white blood cells) and serum glucose occurred. Histopathological results showed that diethyl maleate induced a hoop of edema in the hepatic periportal area; while T.majus methyl alcohol extract or vitamin E prior to diethyl maleate injection shift blood and liver toxicity induced by diethyl maleate towards normal values and preserved hepatic lobular architecture. In conclusion, pre-treatment with either T.majus methyl alcohol extract or vitamin E provide protection against blood and liver toxicity induced by diethyl maleate in rats, these results were confirmed by histological examinations.
    Matched MeSH terms: Liver/drug effects*
  2. Harizal SN, Mansor SM, Hasnan J, Tharakan JK, Abdullah J
    J Ethnopharmacol, 2010 Sep 15;131(2):404-9.
    PMID: 20643198 DOI: 10.1016/j.jep.2010.07.013
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa Korth (ketum) is widely used in Malaysia as a medicinal agent for treating diarrhea, worm infestations and also acts as an analgesic and antipyretic.
    AIM: The aim of the study is to determine the acute toxicity of Mitragyna speciosa Korth standardized methanol extract in vivo in 4-weeks-old Sprague-Dawley rats.
    METHODOLOGY: Rats were orally administrated single dose of 100, 500 and 1000 mg/kg Mitragyna speciosa Korth standardized methanol extract and the control group received 430 mg/kg of morphine orally. There were 10 rats in each group. All animals were sacrificed after 14 days of treatment. Eight parameters were tested: cage side observation, body weight measurement, food and water consumption, blood pressure, absolute and relative organ weight, hematology, biochemical analysis and histopathology, to look for evidence of toxicity.
    RESULT: No mortality was noted after 14 days of treatment. In general, behavior, food and water consumption, hematological studies and organ weights showed no significant changes. The standardized methanol extraction of Mitragyna speciosa Korth increased rat blood pressure (systolic: 147.4+/-1.01, 131.64+/-4.94 and 137.8+/-4.46) after an hour of 100, 500 and 1000 mg/kg doses, respectively. Biochemical studies showed significant elevation of ALT, AST, albumin, triglycerides, cholesterol and albumin (p>0.05), at all levels of doses. But, nephrotoxicity evidenced by elevated creatinine was seen only at a dose of 1000 mg/kg. Histological examination showed congestion of sinusoids, hemorrhage hepatocytes, fatty change, centrilobular necrosis and increased number of Kuppfer cells in the liver of all Mitragyna speciosa Korth standardized methanol extract treated groups.
    CONCLUSION: Oral administration of standardized methanolic extraction of Mitragyna speciosa Korth resulted in increasing rat blood pressure after an hour of drug administration. The highest dose of extract also induced acute severe hepatotoxicity and mild nephrotoxicity. However, Mitragyna speciosa Korth shows no effects on body weight, food and water consumption, absolute and relative organ weight and also hematology parameters.
    Matched MeSH terms: Liver/drug effects*
  3. Hussin M, Hamid AA, Mohamad S, Saari N, Bakar F, Dek SP
    J Food Sci, 2009 Mar;74(2):H72-8.
    PMID: 19323754 DOI: 10.1111/j.1750-3841.2009.01045.x
    A study was carried out to investigate the effects of Centella asiatica leaf on lipid metabolism of oxidative stress rats. The rats were fed 0.1% hydrogen peroxide (H(2)O(2)) with either 0.3% (w/w) C. asiatica extract, 5%C. asiatica powder (w/w), or 0.3% (w/w) alpha-tocopherol for 25 wk. Results of the study showed that C. asiatica powder significantly (P < 0.05) lowered serum low-density lipoprotein compared to that of control rats (rats fed H(2)O(2) only). At the end of the study C. asiatica-fed rats were also found to have significantly (P < 0.05) higher high-density lipoprotein and lower triglyceride level compared to rats fed only normal diet. However, cholesterol level of rats fed both C. asiatica extract and powder was found to be significantly (P < 0.05) higher compared to that of control rats. It was interesting to note that consumption of C. asiatica significantly decreased body and liver weights of the rats. Histological examinations revealed no obvious changes in all rats studied. Quantitative analysis of C. asiatica leaf revealed high concentration of total phenolic compounds, in particular, catechin, quercetin, and rutin.
    Matched MeSH terms: Liver/drug effects
  4. Yaakub H, Masnindah M, Shanthi G, Sukardi S, Alimon AR
    Anim. Reprod. Sci., 2009 Oct;115(1-4):182-8.
    PMID: 19167847 DOI: 10.1016/j.anireprosci.2008.12.006
    Testes from nine male Malin x Santa-Ines rams with an average body weight of 43.1+/-3.53 kg, were used to study the effects of palm kernel cake (PKC) based diet on spermatogenic cells and to assess copper (Cu) levels in liver, testis and plasma in sheep. Animals were divided into three groups and randomly assigned three dietary treatments using restricted randomization of body weight in completely randomized design. The dietary treatments were 60% palm kernel cake plus 40% oil palm frond (PKC), 60% palm kernel cake plus 40% oil palm frond supplemented with 23 mg/kg dry matter of molybdenum as ammonium molybdate [(NH(4))(6)Mo(7)O(24).4H(2)O] and 600 mg/kg dry matter of sulphate as sodium sulphate [Na(2)SO(4)] (PKC-MS) and 60% concentrate of corn-soybean mix+40% oil palm frond (Control), the concentrate was mixed in a ratio of 79% corn, 20% soybean meal and 1% standard mineral mix. The results obtained showed that the number of spermatogonia, spermatocytes, spermatids and Leydig cells were not significantly different among the three treatment groups. However, spermatozoa, Sertoli cells and degenerated cells showed significant changes, which, may be probably due to the Cu content in PKC. Liver and testis Cu levels in the rams under PKC diet was found to be significantly higher (P<0.05) than rams in Control and PKC-MS diets. Plasma Cu levels showed a significant increase (P<0.05) at the end of the experiment as compared to at the beginning of the experiment for PKC and Control. In conclusion, spermatogenesis is normal in rams fed the diet without PKC and PKC supplemented with Mo and S. However spermatogenesis was altered in the PKC based diet probably due to the toxic effects of Cu and the significant changes in organs and plasma. Thus, Mo and S play a major role in reducing the accumulation of Cu in organs.
    Matched MeSH terms: Liver/drug effects
  5. Somchit N, Wong CW, Zuraini A, Ahmad Bustamam A, Hasiah AH, Khairi HM, et al.
    Drug Chem Toxicol, 2006;29(3):237-53.
    PMID: 16777703
    Itraconazole and fluconazole are potent wide spectrum antifungal drugs. Both of these drugs induce hepatotoxicity clinically. The mechanism underlying the hepatotoxicity is unknown. The purpose of this study was to investigate the role of phenobarbital (PB), an inducer of cytochrome P450 (CYP), and SKF 525A, an inhibitor of CYP, in the mechanism of hepatotoxicity induced by these two drugs in vivo. Rats were pretreated with PB (75 mg/kg for 4 days) prior to itraconazole or fluconazole dosing (20 and 200 mg/kg for 4 days). In the inhibition study, for 4 consecutive days, rats were pretreated with SKF 525A (50 mg/kg) or saline followed by itraconazole or fluconazole (20 and 200 mg/kg) Dose-dependent increases in plasma alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma-GT), and alkaline phosphatase (ALP) activities and in liver weight were detected in rats receiving itraconazole treatment. Interestingly, pretreatment with PB prior to itraconazole reduced the ALT and gamma-GT activities and the liver weight of rats. No changes were observed in rats treated with fluconazole. Pretreatment with SKF 525A induced more severe hepatotoxicity for both itraconazole and fluconazole. CYP 3A activity was inhibited dose-dependently by itraconazole treatment. Itraconazole had no effects on the activity of CYP 1A and 2E. Fluconazole potently inhibited all three isoenzymes of CYP. PB plays a role in hepatoprotection to itraconazole-induced but not fluconazole-induced hepatotoxicity. SKF 525A enhanced the hepatotoxicity of both antifungal drugs in vivo. Therefore, it can be concluded that inhibition of CYP may play a key role in the mechanism of hepatotoxicity induced by itraconazole and fluconazole.
    Matched MeSH terms: Liver/drug effects
  6. Grace-Lynn C, Chen Y, Latha LY, Kanwar JR, Jothy SL, Vijayarathna S, et al.
    Molecules, 2012 Nov 23;17(12):13937-47.
    PMID: 23178309 DOI: 10.3390/molecules171213937
    The aim of the present study was to evaluate the hepatoprotective activity of lantadene A against acetaminophen-induced liver toxicity in mice was studied. Activity was measured by monitoring the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin, along with histo-pathological analysis. Silymarin was used as positive control. A bimodal pattern of behavioural toxicity was exhibited by the lantadene A-treated group at the beginning of the treatment. However, treatment with lantadene A and silymarin resulted in an increase in the liver weight compared with the acetaminophen treated group. The results of the acetaminophen-induced liver toxicity experiments showed that mice treated with lantadene A (500 mg/kg) showed a significant decrease in the activity of ALT, AST and ALP and the level of bilirubin, which were all elevated in the acetaminophen treated group (p < 0.05). Histological studies supported the biochemical findings and a maximum improvement in the histoarchitecture was seen. The lantadene A-treated group showed remarkable protective effects against histopathological alterations, with comparable results to the silymarin treated group. The current study confirmed the hepatoprotective effects of lantadene A against the model hepatotoxicant acetaminophen, which is likely related to its potent antioxidative activity.
    Matched MeSH terms: Liver/drug effects
  7. Ponniah J, Muhammad K, Abdullah S, Ganapathy KK, bt Sheikh Abdul Hamid N
    PMID: 15691160
    Three ELISA test kits, the Randox ELISA beta-agonist test kit, Euro-Diagnostica test kit, and Ridascreen beta-agonist test kit, were evaluated for screening of meat and liver for beta-agonist residues in fortified and field-incurred samples. It was found that the Randox beta-agonist test kit was more suitable as a screening tool due to its accuracy, ease of use, and lower cost. The tests were able to detect beta-agonist residues at the minimum level of detection, as claimed by the suppliers. The performance of the method as assessed through recovery rates of beta-agonists in fortified samples was satisfactory with a low coefficient of variation (1-3%). Repeatability, as measured through the coefficient of correlation was also satisfactory. For field-incurred positive samples, the test kit showed a sensitivity of 100% and a low rate of false positives for goat and cow tissues. However, a high rate of apparent false positives was obtained for tissues of swine.
    Matched MeSH terms: Liver/drug effects
  8. 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: Liver/drug effects*
  9. Sabetghadam A, Ramanathan S, Sasidharan S, Mansor SM
    J Ethnopharmacol, 2013 Apr 19;146(3):815-23.
    PMID: 23422336 DOI: 10.1016/j.jep.2013.02.008
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa is a popular medicinal plant in Southeast Asia which is commonly used for its morphine-like effects. Although the analgesic properties of Mitragyna speciosa and its ability to ameliorate withdrawal signs after abrupt cessation of opioid abuse are well known, information about the long-term safety of the plant's active compounds is lacking. In this work, we evaluated the effects of sub-chronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa leaves in rats.

    MATERIALS AND METHODS: Male and female Sprague-Dawley rats received three doses of mitragynine (1, 10, 100mg/kg, p.o) for 28 days respectively. Food intake and relative body weight were measured during the experiment. After completion of drug treatment biochemical, hematological, and histological analyses were performed.

    RESULTS: No mortality was observed in any of the treatment groups. The groups of rats treated with the lower and intermediate doses showed no toxic effects during the study. However, the relative body weight of the group of female rats treated with the 100mg/kg dose was decreased significantly. Food intake also tended to decrease in the same group. Only relative liver weight increased after treatment with the high dose of mitragynine (100mg/ kg) in both the male and female treatment groups of rats. Biochemical and hematological parameters were also altered especially in high dose treatment group which corresponds to the histopathological changes.

    CONCLUSIONS: The study demonstrated that mitragynine is relatively safe at lower sub-chronic doses (1-10mg/kg) but exhibited toxicity at a highest dose (sub-chronic 28 days: 100mg/kg). This was confirmed by liver, kidney, and brain histopathological changes, as well as hematological and biochemical changes.

    Matched MeSH terms: Liver/drug effects
  10. Ansar S, Iqbal M
    Hum Exp Toxicol, 2016 Dec;35(12):1305-1311.
    PMID: 26825963
    The present study was undertaken to evaluate the effect of diallylsulphide (DAS) against mercuric chloride (HgCl2)-induced oxidative stress in rat livers. Rats were randomly divided into four groups of six rats each and exposed to HgCl2 (50 mg/kg/body weight (b.w.)) intraperitoneally and/or DAS (200 mg/kg/b.w.) by gavage. HgCl2 administration enhanced alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels (p < 0.05) with reduction in the levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). However, treatment with DAS markedly attenuated HgCl2-induced biochemical alterations in liver and serum transaminases (AST and ALT; p < 0.05). Further, biochemical results were confirmed by histopathological changes as compared to HgCl2-intoxicated rats. Histopathology of liver also showed that administration of DAS significantly reduced the damage generated by HgCl2 The present study suggests that DAS shows antioxidant activity and plays a protective role against mercury-induced oxidative damage in the rat livers.
    Matched MeSH terms: Liver/drug effects
  11. Lau CL, Chan ST, Selvaratanam M, Khoo HW, Lim AY, Modamio P, et al.
    Fundam Clin Pharmacol, 2015 Aug;29(4):404-16.
    PMID: 26011058 DOI: 10.1111/fcp.12126
    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P < 0.05), was higher in liver and brain (P < 0.001), and lower in kidney (P < 0.001) vs. male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P < 0.01), brain, liver, and kidney (all P < 0.001). However, in male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P < 0.001). The tissue-to-plasma AUC0→∞ ratio was similar between male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P < 0.001) while remained unchanged in female mice and in kidney (male and female mice) but decreased 55% in brain (P < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.
    Matched MeSH terms: Liver/drug effects
  12. Yaacob NS, Yankuzo HM, Devaraj S, Wong JK, Lai CS
    PLoS One, 2015;10(5):e0126426.
    PMID: 26000968 DOI: 10.1371/journal.pone.0126426
    Cancer patients seek alternative remedies such as traditional medicinal plants for safe and effective treatment and help overcome the side effects of conventional therapy. Current knowledge indicates that extracts of Strobilanthes crispus of the Acanthaceae family exhibit potent anticancer properties in vitro and are non-toxic in vivo. S. crispus was also reported to be protective against chemical hepatocarcinogenesis. We previously showed that a bioactive fraction of S. crispus leaves also synergized with tamoxifen to cause apoptosis of human breast cancer cell lines without damaging non-malignant epithelial cells. The present study aimed to evaluate the antitumor effect of S. crispus dichloromethane fraction (F3) using N-methyl-N-Nitrosourea (NMU)-induced rat mammary tumor model. Tumor regression was observed in 75% of the rats following 8-week oral administration of F3 with no secondary tumour formation and no signs of anemia or infection. However, no improvement in the liver and renal function profiles was observed. Major constituents of F3 were identified as lutein, 131-hydroxy-132-oxo-pheophytin a, campesterol, stigmasterol, β-sitosterol, pheophytin a and 132-hydroxy-pheophytin a. These compounds however, may not significantly contribute to the antitumor effect of F3.
    Matched MeSH terms: Liver/drug effects
  13. Mohamed MI, Mohammad MK, Abdul Razak HR, Abdul Razak K, Saad WM
    Biomed Res Int, 2015;2015:183525.
    PMID: 26075217 DOI: 10.1155/2015/183525
    Emerging syntheses and findings of new metallic nanoparticles (MNPs) have become an important aspect in various fields including diagnostic imaging. To date, iodine has been utilized as a radiographic contrast medium. However, the raise concern of iodine threats on iodine-intolerance patient has led to search of new contrast media with lower toxic level. In this animal modeling study, 14 nm iron oxide nanoparticles (IONPs) with silane-polyethylene glycol (SiPEG) and perchloric acid have been assessed for toxicity level as compared to conventional iodine. The nanotoxicity of IONPs was evaluated in liver biochemistry, reactive oxygen species production (ROS), lipid peroxidation mechanism, and ultrastructural evaluation using transmission electron microscope (TEM). The hematological analysis and liver function test (LFT) revealed that most of the liver enzymes were significantly higher in iodine-administered group as compared to those in normal and IONPs groups (P < 0.05). ROS production assay and lipid peroxidation indicator, malondialdehyde (MDA), also showed significant reductions in comparison with iodine group (P < 0.05). TEM evaluation yielded the aberration of nucleus structure of iodine-administered group as compared to those in control and IONPs groups. This study has demonstrated the less toxic properties of IONPs and it may postulate that IONPs are safe to be applied as radiographic contrast medium.
    Matched MeSH terms: Liver/drug effects
  14. Tan BL, Kassim NM, Mohd MA
    Toxicol Lett, 2003 Aug 28;143(3):261-70.
    PMID: 12849686
    The effects of bisphenol A and nonylphenol on pubertal development in the intact juvenile/peripubertal male Sprague-Dawley rats was observed in this study from PND23-52/53. Two groups of rats were administered orally with either 100 mg/kg body weight of nonylphenol or bisphenol A. Another group of rats were administered orally with a mixture of 100 mg/kg body weight of nonylphenol and bisphenol A. Control group was administered with the vehicle of Tween-80 with corn oil (1:9 v/v). Observations made in this study included growth, age at preputial separation, thyroid, liver, testis and kidney weight and histology, epididymal and seminal vesicle plus coagulation gland weight. Nonylphenol and bisphenol A have been observed to cause delay in puberty onset as well as testicular damage in the treatment groups when compared to the control; spermatogenesis was affected in most treated rats. Bisphenol A also caused the enlargement of the kidney and hydronephrosis. Administration of nonylphenol and bisphenol A as a mixture has caused less than additive effects.
    Matched MeSH terms: Liver/drug effects
  15. Makpol S, Shamaan NA, Jarien Z, Top AG, Khalid BA, Wan Ngah WZ
    Gen. Pharmacol., 1997 Apr;28(4):589-92.
    PMID: 9147029
    1. alpha-Tocopherol (alpha-T) and gamma-tocotrienol (gamma-T) were supplemented continuously for 8 weeks in the diets of normal rats and rats chemically induced with cancer using diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF) and partial hepatectomy. Hepatocarcinogenesis was followed by determining the plasma gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activities as well as placental glutathione S-transferase (PGST) and GGT activities histochemically, at 4-week intervals. 2. Male Rattus norvegicus were supplemented alpha-T and gamma-T at two different doses of 30 and 300 mg/kg diet. The supplementation was started at three different times: simultaneously with DEN administration; 4 weeks; and 8 weeks after DEN administration. 3. Elevation of plasma GGT activities and formation of PGST and GGT positive foci were attenuated significantly (P < 0.05) when alpha-T and gamma-T were supplemented simultaneously with cancer induction. Supplementation begun 4 and 8 weeks after cancer induction did not affect plasma enzyme activities and formation of enzyme-positive foci. 4. alpha-T was more effective than gamma-T, and a lower dose of 30 mg/kg was found to be more effective in reducing the severity of hepatocarcinogenesis.
    Matched MeSH terms: Liver/drug effects*
  16. Pihie AH, Stanslas J, Din LB
    Anticancer Res, 1998 May-Jun;18(3A):1739-43.
    PMID: 9673398
    The antiproliferative activity of a styrylpyrone derivative (SPD) plant extract, was studied in three different human breast cancer cell lines in culture, and was compared with tamoxifen. The number of living cells was evaluated by Methylene Blue staining technique. SPD showed strong antiproliferative activity in estrogen receptor (ER) and progestin receptor (PgR) positive MCF-7 cells (EC50 = 6.30 x 10(-7) M) and receptor-negative MDA-MB-231 (EC50 = 5.62 x 10(-7) M), but it partially inhibited the high progestin receptor positive T47D cells (EC50 = 1.58 x 10(-6) M). Whereas tamoxifen, a nonsteroidal antiestrogen exhibited strong inhibition on MCF-7 cells (EC50 = 1.41 x 10(-6) M) and partial inhibition on T47D cells (EC50 = 2.5 x 10(-6) M), but did not affect the MDA-MB-231 cells in the concentration range 0.1 nM-1 microM (EC50 = 5.01 microM). At the same concentration range SPD and tamoxifen did not inhibit the proliferation of normal human liver cell line CCL 13 and normal bovine kidney MDBK; whereas adriamycin, a common chemotherapy drug for the treatment of advance cancer, caused 95% inhibition at 10(-6) M. Competitive binding studies showed SPD had no ability to inhibit the binding of [3H]estradiol and [3H]progesterone to ER and PgR, respectively but, tamoxifen exhibited affinity for ER. Therefore, it can be concluded that the antiproliferative activity of SPD was selective towards breast cancer cell lines and not mediated by ER or PgR.
    Matched MeSH terms: Liver/drug effects
  17. Umpleby AM, Shojaee-Moradie F, Fielding B, Li X, Marino A, Alsini N, et al.
    Clin Sci (Lond), 2017 Nov 01;131(21):2561-2573.
    PMID: 28923880 DOI: 10.1042/CS20171208
    Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n = 11) and low liver fat 'controls' (n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the high (P<0.02) and low sugar (P<0.0002) diets, a lower VLDL1-TAG fractional catabolic rate after the high sugar diet (P<0.01), and a higher VLDL1-TAG production rate after the low sugar diet (P<0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL1-TAG (P<0.02) in the controls, but in contrast, a higher production of VLDL2-TAG (P<0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. The present study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars.
    Matched MeSH terms: Liver/drug effects
  18. Baki MA, Shojib MFH, Sehrin S, Chakraborty S, Choudhury TR, Bristy MS, et al.
    Environ Geochem Health, 2020 Feb;42(2):531-543.
    PMID: 31376046 DOI: 10.1007/s10653-019-00386-4
    This study aimed to assess the effects of major ecotoxic heavy metals accumulated in the Buriganga and Turag River systems on the liver, kidney, intestine, and muscle of common edible fish species Puntius ticto, Heteropneustes fossilis, and Channa punctatus and determine the associated health risks. K was the predominant and reported as a major element. A large concentration of Zn was detected in diverse organs of the three edible fishes compared with other metals. Overall, trace metal analysis indicated that all organs (especially the liver and kidney) were under extreme threat because the maximum permissible limit set by different international health organizations was exceeded. The target hazard quotient and target cancer risk due to the trace metal content were the largest for P. ticto. Thus, excessive intake of P. ticto from the rivers Buriganga and Turag could result in chronic risks associated with long-term exposure to contaminants. Histopathological investigations revealed the first detectable indicators of infection and findings of long-term injury in cells, tissues, and organs. Histopathological changes in various tissue structures of fish functioned as key pointers of connection to pollutants, and definite infections and lesion types were established based on biotic pointers of toxic/carcinogenic effects. The analysis of histopathological alterations is a controlling integrative device used to assess pollutants in the environment.
    Matched MeSH terms: Liver/drug effects
  19. Gautam A, Paudel YN, Abidin S, Bhandari U
    Hum Exp Toxicol, 2019 Mar;38(3):356-370.
    PMID: 30526076 DOI: 10.1177/0960327118817862
    The current study investigated the role of guggulsterone (GS), a farnesoid X receptor antagonist, in the choline metabolism and its trimethylamine (TMA)/flavin monooxygenases/trimethylamine-N-oxide (TMAO) inhibiting potential in a series of in vitro and in vivo studies as determined by high-performance liquid chromatography (HPLC), mass spectroscopy (MS), and liquid chromatography (LC)-MS techniques. Atherosclerosis (AS) was successfully induced in a group of experimental animals fed with 2% choline diet for 6 weeks. Serum lipid profiles such as total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were measured. Pro-inflammatory cytokines levels, markers for a hepatic injury, and oxidative stress markers were assessed. Interestingly, GS reduced the level of TMA/TMAO in both in vitro and in vivo studies as demonstrated by the peaks obtained from HPLC, MS, and LC-MS. Furthermore, GS exhibited cardioprotective and antihyperlipidemic effects as evidenced by the attenuation of levels of several serum lipid profiles and different atherogenic risk predictor indexes. GS also prevented hepatic injury by successfully restoring the levels of hepatic injury biomarkers to normal. Similarly, GS inhibited the production of pro-inflammatory cytokines levels, as well as GS, enhanced antioxidant capacity, and reduced lipid peroxidation. Histopathological study of aortic sections demonstrated that GS maintained the normal architecture in AS-induced rats. On the basis of results obtained from current investigation, we suggest that GS might have a great therapeutic potential for the treatment of AS.
    Matched MeSH terms: Liver/drug effects
  20. Eleazu C, Ekeleme CE, Famurewa A, Mohamed M, Akunna G, David E, et al.
    PMID: 30659555 DOI: 10.2174/1871530319666190119101058
    BACKGROUND: Research studies that holistically investigated the effect of administration of Virgin Coconut Oil (VCO) on diabetic humans or animals are limited in literature.

    OBJECTIVE: To investigate the effect of administration of VCO on lipid profile, markers of hepatic and renal dysfunction, and hepatic and renal antioxidant activities of alloxan induced diabetic rats.

    METHODS: Twenty-four male albino rats were used, and they were divided into four groups of six rats each. Group 1 (Normal Control, NC) received distilled water (1 mL/kg); Group 2 (VCO Control) received VCO (5 mL/kg); Group 3 (Diabetic Control, DC) received distilled water (1 mL/kg); Group 4 (Test Group, TG) received 5 ml/kg of VCO.

    RESULTS: There were no significant differences in blood glucose, body weights, relative liver weights, relative kidney weights, hepatic and renal Superoxide Dismutase (SOD) activities, Malondialdehyde (MDA), albumin, aspartate Amino Transaminase (AST), alanine Amino Transaminase (ALT), Alkaline Phosphatase (ALP), urea, creatinine, uric acid, total cholesterol, triacylglycerol, Very Low Density Lipoprotein cholesterol (VLDL) and Low Density Lipoprotein cholesterol (LDL) concentrations; significant increases in renal Glutathione (GSH), hepatic catalase, Glutathione Peroxidase (GPx) and GSH but significant reduction in renal GPx and catalase activities of VCO control group compared with NC group. There were significant increases in blood glucose, relative liver and kidney weights, hepatic GPx, hepatic and renal MDA concentration, ALP, AST, ALT, urea, creatinine, uric acid, triacylglycerol, total cholesterol, LDL and VLDL concentrations; and significant decreases in body weight, hepatic SOD and GSH activities and albumin concentration but no significant difference in hepatic catalase activity of DC group compared with NC group. Administration of VCO to diabetic rats positively modulated these parameters compared with the diabetic control.

    CONCLUSION: The study showed the potentials of VCO in the management of hyperlipidemia, renal and hepatic dysfunctions imposed by hyperglycemia and by oxidative stress in diabetic rats.

    Matched MeSH terms: Liver/drug effects
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links