Displaying publications 1 - 20 of 31 in total

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  1. Jarrar QB, Hakim MN, Cheema MS, Zakaria ZA
    Ultrastruct Pathol, 2017 8 23;41(5):335-345.
    PMID: 28829237 DOI: 10.1080/01913123.2017.1349850
    Mefenamic acid (MFA) is used as an anti-inflammatory, antinociceptive, and antipyretic agent for treatment of a wide range of pathological disorders. While the uncertainty of its safety and the poor oral bioavailability constitute the major limiting factors of its medical use, considerable efforts including liposomal encapsulation are needed to achieve maximum therapeutic advantages. The current work was conducted to investigate the ultrastructural alterations in the liver induced by free MFA and its liposomal preparation. Female Sprague-Dawley rats were treated with daily oral doses of either free MFA or MFA entrapped in Tween 80 inoculated liposomes at the concentration of 80 mg/kg for 28 days. Ultrathin sections were prepared from biopsies taken from the liver of each member of all animals under study and subjected to examination by transmission electron microscopy. The liver of rats that were exposed to liposomal MFA showed more ultrastructural alterations than the rats treated with the free drug. While both groups of rats demonstrated sinusoidal dilatation, Kupffer cell hyperplasia, mitochondrial damage, and nuclear alterations, rats treated with liposome-encapsulated MFA induced an increase in the multiple lysosomes formation, hepatocytic steatosis, and apoptotic activity than free MFA-treated rats. The ultrastructural findings of the present study indicate that the use of liposomal MFA induces more hepatic damage than the use of free MFA.
    Matched MeSH terms: Hepatocytes/drug effects
  2. Awang N, Kamaludin NF, Ghazali AR
    Pak J Biol Sci, 2011 Aug 01;14(15):768-74.
    PMID: 22303582
    Cancer is one of the main causes of mortality and morbidity in world. New compounds are currently being synthesized to combat this disease. The organotins are gaining more attention as anti-cancer agents due to their potent cytotoxicity properties. In this study, a series of newly synthesized organotins namely dimethyltin (IV) (compound 1), dibutyltin (IV) (compound 2) and triphenyltin (IV) benzylisopropyldithiocarbamate (compound 3) were assessed for their cytotoxic activities against human Chang liver cells and hepatocarcinoma HepG2 cells. The cytotoxicity of these organotins in both cells upon 24 h treatment was assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Compound 2 and 3 exhibited potent cytotoxic activities towards both cells where the IC50 values were less then 10 microM. The IC50 value for compound 2 was 2.5 microM in Chang liver cells and 7.0 microM in HepG2 cells whereas compound 3 exhibited an IC50 value of 1.5 microM in Chang liver cells and 2.5 microM in HepG2 cells. Therefore, compound 2 and 3 were more toxic against human Chang liver cells as compared to hepatocarcinoma HepG2 cells. Interestingly, compound 1 did not have any IC50 value in both cells and hence can be classified as non-toxic. In conclusion, organotin (IV) benzylisopropyldithiocarbamate with insertion of dibutyl and triphenyl functional group possess potent cytotoxicity properties. Structural modification of these compounds can be carried out in further studies to produce less or non toxic effects towards normal human cell.
    Matched MeSH terms: Hepatocytes/drug effects*
  3. Oskoueian E, Abdullah N, Idrus Z, Ebrahimi M, Goh YM, Shakeri M, et al.
    PMID: 25273634 DOI: 10.1186/1472-6882-14-368
    Palm kernel cake (PKC), the most abundant by-product of oil palm industry is believed to contain bioactive compounds with hepatoprotective potential. These compounds may serve as hepatoprotective agents which could help the poultry industry to alleviate adverse effects of heat stress on liver function in chickens.
    Matched MeSH terms: Hepatocytes/drug effects*
  4. Hu L, Yu W, Li Y, Prasad N, Tang Z
    Biomed Res Int, 2014;2014:341291.
    PMID: 24719856 DOI: 10.1155/2014/341291
    The antioxidant activities and protective effects of total phenolic extracts (TPE) and their major components from okra seeds on oxidative stress induced by carbon tetrachloride (CCl4) in rat hepatocyte cell line were investigated. The major phenolic compounds were identified as quercetin 3-O-glucosyl (1 → 6) glucoside (QDG) and quercetin 3-O-glucoside (QG). TPE, QG, and QDG from okra seeds exhibited excellent reducing power and free radical scavenging capabilities including α, α-diphenyl-β-picrylhydrazyl (DPPH), superoxide anions, and hydroxyl radical. Overall, DPPH radical scavenging activity and reducing power of QG and QDG were higher than those of TPE while superoxide and hydroxyl radical scavenging activities of QG and TPE were higher than those of QDG. Furthermore, TPE, QG, and QDG pretreatments significantly alleviated the cytotoxicity of CCl4 on rat hepatocytes, with attenuated lipid peroxidation, increased SOD and CAT activities, and decreased GPT and GOT activities. The protective effects of TPE and QG on rat hepatocytes were stronger than those of QDG. However, the cytotoxicity of CCl4 on rat hepatocytes was not affected by TPE, QG, and QDG posttreatments. It was suggested that the protective effects of TPE, QG, and QDG on rat hepatocyte against oxidative stress were related to the direct antioxidant capabilities and the induced antioxidant enzymes activities.
    Matched MeSH terms: Hepatocytes/drug effects*
  5. Oskoueian E, Abdullah N, Zulkifli I, Ebrahimi M, Karimi E, Goh YM, et al.
    BMC Complement Altern Med, 2015 Oct 30;15:392.
    PMID: 26518905 DOI: 10.1186/s12906-015-0921-z
    BACKGROUND: Palm kernel cake (PKC), a by-product of the palm oil industry is abundantly available in many tropical and subtropical countries. The product is known to contain high levels of phenolic compounds that may impede the deleterious effects of fungal mycotoxins. This study focused on the evaluation of PKC phenolics as a potential cytoprotective agent towards aflatoxin B1 (AFB1)-induced cell damage.

    METHODS: The phenolic compounds of PKC were obtained by solvent extraction and the product rich in phenolic compounds was labeled as phenolic-enriched fraction (PEF). This fraction was evaluated for its phenolic compounds composition. The antioxidant activity of PEF was determined by using 1,1-diphenyl-2-picryl-hydrazil scavenging activity, ferric reducing antioxidant power, inhibition of ß-carotene bleaching, and thiobarbituric acid reactive substances assays. The cytotoxicity assay and molecular biomarkers analyses were performed to evaluate the cytoprotective effects of PEF towards aflatoxin B1 (AFB1)-induced cell damage.

    RESULTS: The results showed that PEF contained gallic acid, pyrogallol, vanillic acid, caffeic acid, syringic acid, epicatechin, catechin and ferulic acid. The PEF exhibited free radical scavenging activity, ferric reducing antioxidant power, ß-carotene bleaching inhibition and thiobarbituric acid reactive substances inhibition. The PEF demonstrated cytoprotective effects in AFB1-treated chicken hepatocytes by reducing the cellular lipid peroxidation and enhancing antioxidant enzymes production. The viability of AFB1-treated hepatocytes was improved by PEF through up-regulation of oxidative stress tolerance genes and down-regulation of pro-inflammatory and apoptosis associated genes.

    CONCLUSIONS: The present findings supported the proposition that the phenolic compounds present in PKC could be a potential cytoprotective agent towards AFB1 cytotoxicity.

    Matched MeSH terms: Hepatocytes/drug effects*
  6. Mamikutty N, Thent ZC, Haji Suhaimi F
    Biomed Res Int, 2015;2015:895961.
    PMID: 26273656 DOI: 10.1155/2015/895961
    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD.

    AIMS: In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis.

    METHODS: The concentration of fructose-drinking water (FDW) used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph.

    RESULTS: After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density.

    CONCLUSION: We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.

    Matched MeSH terms: Hepatocytes/drug effects*
  7. Abdull Razis AF, Konsue N, Ioannides C
    Mol Nutr Food Res, 2018 09;62(18):e1700916.
    PMID: 29288567 DOI: 10.1002/mnfr.201700916
    The potential of isothiocyanates to antagonize the carcinogenicity of structurally diverse chemicals has been established in animals. A feasible mechanism of action involves protecting DNA by reducing the availability of the genotoxic metabolites of chemical carcinogens by either inhibiting their generation and/or stimulating their detoxification. In vivo as well as in vitro studies conducted in rat/human primary hepatocytes and precision-cut tissue slices have revealed that isothiocyanates can impair cytochrome P450 activity, including the CYP1 family which is the most active in the bioactivation of carcinogens, by virtue of being mechanism-based inactivators. The aromatic phenethyl isothiocyanate is the most effective of those studied, whereas aliphatic isothiocyanates such as sulforaphane and erucin necessitate high doses in order to manifest such effects that may not always be achievable through the diet. In all systems studied, isothiocyanates are strong inducers of detoxification enzyme systems including quinone reductase, glutathione S-transferase, epoxide hydrolase, and UDP-glucuronosyl transferase. Indeed, in smokers phenethyl isothiocyanate intake increases the urinary excretion of inactive mercapturate metabolites of toxic chemicals present in tobacco. Glucosinolates, the precursors of isothiocyanates, have also the potential to upregulate detoxification enzyme systems, but their contribution to the cancer chemoprevention linked to cruciferous vegetable consumption remains to be evaluated.
    Matched MeSH terms: Hepatocytes/drug effects
  8. Marlini M, Mabuchi A, Mallard BL, Hairulhisyam N, Akashi-Takamura S, Harper JL, et al.
    Exp Physiol, 2016 12 01;101(12):1492-1505.
    PMID: 27634415 DOI: 10.1113/EP085727
    NEW FINDINGS: What is the central question of this study? The liver regenerative process is complex and involves a sequence of signalling events, but the possible involvement of structural and haemodynamic changes in vivo during this process has never been explored. What is the main finding and its importance? Normal sinusoidal blood flow and velocity are crucial for a normal regenerative response, and delays in these haemodynamic events resulted in impaired liver regeneration in lipopolysaccharide-insensitive, C3H/HeJ mice. Toll-like receptor 4 signalling is required for restoration of normal liver architecture during the liver regenerative process. Liver regeneration is delayed in mice with a defective Toll-like receptor 4 (TLR4; C3H/HeJ mice) but is normal in TLR4 knockouts (TLR4-/- ). Here, we investigated the possible involvement of structural and haemodynamic changes in vivo in the underlying mechanism. In lipopolysaccharide-sensitive (C3H/HeN and C57BL/6) and lipopolysaccharide-insensitive (C3H/HeJ and TLR4-/- ) mice, a 70% partial hepatectomy (PH) was performed under inhalational anaesthesia. At days 3 and 7 after PH, the hepatic microcirculation was interrogated using intravital microscopy. Delayed liver regeneration was confirmed in C3H/HeJ, but not in C3H/HeN, C57BL/6 (WT) or TLR4-/- mice by liver weight-to-body-weight ratio, the percentage of proliferating cell nuclear antigen (PCNA)-positive cells and mitotic index data. At day 3 after PH, sinusoidal red blood cell velocity increased by 100% in C3H/HeN mice, but by only 40% in C3H/HeJ mice. Estimated sinusoidal blood flow was significantly higher at day 7 after PH in C3H/HeN than in C3H/HeJ mice. The hepatic cord width was significantly larger in C3H/HeN than in C3H/HeJ mice at day 3 and it was significantly larger in TLR4-/- than in C57BL/6 WT mice at day 7 after PH. Hepatocyte nucleus density and functional sinusoidal density was significantly reduced at days 3 and 7 after PH in all mouse strains compared with their zero-time controls. Functional sinusoidal density was significantly lower in C3H/HeJ compared with C3H/HeN mice at day 7 after PH. The present study indicates that altered sinusoidal blood flow and velocity in C3H/HeJ mice may contribute to the observed delay in the regenerative response in these mice. In addition, restoration of normal liver architecture may be delayed in TLR4-/- mice.
    Matched MeSH terms: Hepatocytes/drug effects
  9. 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: Hepatocytes/drug effects
  10. Kamisan FH, Yahya F, Mamat SS, Kamarolzaman MF, Mohtarrudin N, Kek TL, et al.
    PMID: 24708543 DOI: 10.1186/1472-6882-14-123
    Dicranopteris linearis (family Gleicheniaceae) has been reported to possess anti-inflammatory and antioxidant activities but no attempt has been made to study its hepatoprotective potential. The aim of the present study was to determine the hepatoprotective effect of methanol extracts of D. linearis (MEDL) against carbon tetrachloride (CCl4)-induced acute liver injury in rats.
    Matched MeSH terms: Hepatocytes/drug effects
  11. Hussein MZ, Al Ali SH, Zainal Z, Hakim MN
    Int J Nanomedicine, 2011;6:1373-83.
    PMID: 21796241 DOI: 10.2147/IJN.S21567
    An ellagic acid (EA)-zinc layered hydroxide (ZLH) nanohybrid (EAN) was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO) as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8' position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host-guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA.
    Matched MeSH terms: Hepatocytes/drug effects
  12. Yusof KM, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ
    Molecules, 2015 Jun 03;20(6):10280-97.
    PMID: 26046324 DOI: 10.3390/molecules200610280
    Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0-150 µg/mL) and 6G (0-300 µg/mL) on the cells. The half maximal inhibitory concentration (IC50) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells.
    Matched MeSH terms: Hepatocytes/drug effects
  13. Chen YF, Chong CL, Wu YC, Wang YL, Tsai KN, Kuo TM, et al.
    PLoS One, 2015;10(6):e0131743.
    PMID: 26121644 DOI: 10.1371/journal.pone.0131743
    Hepatitis B virus reactivation is an important medical issue in cancer patients who undergo systemic chemotherapy. Up to half of CHB carriers receiving chemotherapy develop hepatitis and among these cases a notable proportion are associated with HBV reactivation. However, the molecular mechanism(s) through which various chemotherapeutic agents induce HBV reactivation is not yet fully understood. In this study, we investigated the role of the cell cycle regulator p21 (Waf1/Cip1) in the modulation of HBV replication when a common chemotherapeutic agent, doxorubicin, is present. We showed that p21 expression was increased by doxorubicin treatment. This elevation in p21 expression enhanced the expression of CCAAT/enhancer-binding protein α (C/EBPα); such an increase is likely to promote the binding of C/EBPα to the HBV promoter, which will contribute to the activation of HBV replication. Our current study thus reveals the mechanism underlying doxorubicin modulation of HBV replication and provides an increased understanding of HBV reactivation in CHB patients who are receiving systemic chemotherapy.
    Matched MeSH terms: Hepatocytes/drug effects
  14. Somchit N, Hassim SM, Samsudin SH
    Hum Exp Toxicol, 2002 Jan;21(1):43-8.
    PMID: 12046723
    This current study was to investigate the in vitro cytotoxicity of rat hepatocytes induced by the antifungal drugs, itraconazole and fluconazole. Both antifungal drugs caused dose-dependent cytotoxicity. In vitro incubation of hepatocytes with itraconazole revealed significantly higher lactate dehydrogenase (LDH) leakage when compared to fluconazole. Phenobarbital pretreated hepatocytes contained significantly higher total cytochrome P450 content than the control hepatocytes. P450 content was reduced approximately 30% for both types of hepatocytes after 6 hours incubation. Interestingly, cytotoxicity of itraconazole was reduced significantly by phenobarbital pretreatment. Phenobarbital did not have any effect on the cytotoxicity induced by fluconazole. These results demonstrate the in vitro toxicity of hepatocytes induced by itraconazole and fluconazole that were expressed in a dose- and time-dependent manner. Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro.
    Matched MeSH terms: Hepatocytes/drug effects*
  15. Alomari M, Taha M, Imran S, Jamil W, Selvaraj M, Uddin N, et al.
    Bioorg Chem, 2019 11;92:103235.
    PMID: 31494327 DOI: 10.1016/j.bioorg.2019.103235
    Hybrid bis-coumarin derivatives 1-18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ± 0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ± 0.01), 9 (IC50 = 2.4 ± 0.05), 10 (IC50 = 2.25 ± 0.05) and 16 (IC50 = 0.12 ± 0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ± 0.21 µM). To find structure-activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic.
    Matched MeSH terms: Hepatocytes/drug effects
  16. Choi EM, Kim YH
    Food Chem Toxicol, 2008 Jan;46(1):375-9.
    PMID: 17904263 DOI: 10.1016/j.fct.2007.08.018
    The present study was undertaken to determine whether Ligularia fischeri leaf extract (LF) is efficacious against collagen-induced arthritis (CIA) in mice. DBA/1J mice were immunized with bovine type II collagen and treated with LF (100 and 200 mg/kg) for 49 days. Mice were assessed regularly for signs of arthritis and the levels of rheumatoid factor, anti-type II collagen antibody, cytokines, AST, ALT, and creatinine in serum were also examined after the animals were killed. The arthritis score and paw edema were markedly suppressed in the groups treated with LF. Moreover, levels of rheumatoid factor, anti-type II collagen antibody, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 in sera were reduced by LF administration. These data suggest that L. fischeri might be effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.
    Matched MeSH terms: Hepatocytes/drug effects
  17. Sharif R, Ghazali AR, Rajab NF, Haron H, Osman F
    Food Chem Toxicol, 2008 Jan;46(1):368-74.
    PMID: 17900779
    Malaysian locally processed raw food products are widely used as main ingredients in local cooking. Previous studies showed that these food products have a positive correlation with the incidence of cancer. The cytotoxicity effect was evaluated using MTT assay (3-(4,5-dimetil-2-thiazolil)-2,5-diphenyl-2H-tetrazolium bromide) against Chang liver cells at 2000 microg/ml following 72 h incubation. Findings showed all methanol extracts caused a tremendous drop in the percentage of cell viability at 2000 microg/ml (shrimp paste - 41.69+/-3.36%, salted fish - 37.2+/-1.06%, dried shrimp - 40.32+/-1.8%, p<0.05). To detect DNA damage in a single cell, alkaline Comet Assay was used. None of the extracts caused DNA damage to the Chang liver cells at 62.5 microg/ml following 24 h incubation, as compared to the positive control, hydrogen peroxide (tail moment - 9.50+/-1.50; tail intensity - 30.50+/-2.50). Proximate analysis which was used for the evaluation of macronutrients in food showed that shrimp paste did not comply with the protein requirement (<25%) as in Food Act 1983. Salt was found in every sample with the highest percentage being detected in shrimp paste which exceeded 20%. Following heavy metal analysis (arsenic, cadmium, lead and mercury), arsenic was found in every sample with dried shrimps showing the highest value as compared to the other samples (6.16 mg/kg). In conclusion, several food extracts showed cytotoxic effect but did not cause DNA damage against Chang liver cells. Salt was found as the main additive and arsenic was present in every sample, which could be the probable cause of the toxicity effects observed.
    Matched MeSH terms: Hepatocytes/drug effects
  18. Ravindran R, Jaganathan R, Periandavan K
    Cell Biochem Funct, 2020 Apr;38(3):309-318.
    PMID: 31926118 DOI: 10.1002/cbf.3490
    The aim is to test the hypothesis whether the cholesterol loaded lysosomes are capable of mediating lysosomal membrane permeabilization (LMP) during aging and to study the efficacy of epigallocatechin-3-gallate (EGCG) in preserving the lysosomal membrane stability. Aged rats were fed with high cholesterol diet (HCD) and treated with EGCG orally. Serum and tissue lipid status, cholesterol levels in lysosomal fraction, activities of lysosomal enzymes in lysosomal, and cytosolic fractions were measured. Transmission electron microscopic studies (TEM), oil red "O" (ORO) staining, and immunohistochemical analysis of oxidized low density lipoprotein (OxLDL) were carried out. Significant increase in serum, tissue lipid profile, and lysosomal cholesterol levels were observed in aged HCD-fed rats with a concomitant decrease in high density lipoprotein (HDL) levels. We also observed a significant increase in lipid accumulation in hepatocytes of aged HCD-fed rats by TEM, ORO, and immunohistochemical staining. Upon treatment with EGCG to aged HCD-fed animals, we found augmented levels of HDL with a concomitant decrease in lysosomal cholesterol levels and other lipoproteins. TEM studies and immunohistochemistry of OxLDL also showed a marked reduction in lipid deposition of hepatocytes. Thus, EGCG has preserved the lysosomal membrane stability in HCD stressed aged rats. SIGNIFICANCE OF THE STUDY: The research article is focused mainly on the effect of EGCG and its capability on mitigating the release of lysosomal enzymes in aged animals fed with HCD. The study signifies the cellular function of the organelle lysosome following administration of aged rats with HCD, which would make the readers to understand the action of EGCG and the interrelationship of both cholesterol and activity of lysosomes when cholesterol is loaded.
    Matched MeSH terms: Hepatocytes/drug effects
  19. 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: Hepatocytes/drug effects
  20. Nna VU, Bakar ABA, Mohamed M
    Life Sci, 2018 Oct 15;211:40-50.
    PMID: 30205096 DOI: 10.1016/j.lfs.2018.09.018
    AIMS: Hepatic oxidative stress and weak antioxidant defence system resulting in hepatic lesion, has been reported in diabetic rats. The present study investigated the possible hepatoprotective effects of Malaysian propolis (MP) in diabetic rats, on the background that MP has been reported to have anti-hyperglycemic, antioxidant and anti-inflammatory effects.

    MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into 5 groups, namely: normal control (NC), diabetic control (DC), diabetic on 300 mg/kg b.w. MP, diabetic on 300 mg/kg b.w. metformin, and diabetic on MP and metformin combined therapy. Treatment was done orally for 4 weeks, and NC and DC groups received distilled water as vehicle.

    KEY FINDINGS: Results showed increased fasting blood glucose and serum markers of hepatic lesion (aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase and gamma-glutamyl transferase), increased hepatic lactate dehydrogenase activity, decreased hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase activities, increased immunoexpressions of nuclear factor kappa B, tumor necrosis factor-α, interleukin(IL)-1β and caspase-3, and decreased immunoexpressions of IL-10 and proliferating cell nuclear antigen in the liver of DC group. Histopathology of the liver revealed numerous hepatocytes with pyknotic nuclei and inflammatory infiltration, while periodic acid-schiff staining decreased in the liver of DC group. Treatment with MP attenuated these negative effects and was comparable to metformin. Furthermore, these effects were better attenuated in the combined therapy-treated diabetic rats.

    SIGNIFICANCE: Malaysian propolis attenuates hepatic lesion in DM and exerts a synergistic protective effect with the anti-hyperglycemic medication, metformin.

    Matched MeSH terms: Hepatocytes/drug effects*
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