Displaying publications 121 - 140 of 206 in total

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  1. Fulltext Lipoprotein lipase expression, serum lipid and tissue lipid deposition in orally-administered glycyrrhizic acid-treated rats
    Lim WY, Chia YY, Liong SY, Ton SH, Kadir KA, Husain SN
    Lipids Health Dis, 2009;8:31.
    PMID: 19638239 DOI: 10.1186/1476-511X-8-31
    The metabolic syndrome (MetS) is a cluster of metabolic abnormalities comprising visceral obesity, dyslipidaemia and insulin resistance (IR). With the onset of IR, the expression of lipoprotein lipase (LPL), a key regulator of lipoprotein metabolism, is reduced. Increased activation of glucocorticoid receptors results in MetS symptoms and is thus speculated to have a role in the pathophysiology of the MetS. Glycyrrhizic acid (GA), the bioactive constituent of licorice roots (Glycyrrhiza glabra) inhibits 11beta-hydroxysteroid dehydrogenase type 1 that catalyzes the activation of glucocorticoids. Thus, oral administration of GA is postulated to ameliorate the MetS.
    Matched MeSH terms: Liver/drug effects
  2. Comparative study of immunopathophysiological responses induced by B. melitensis and its lipopolysaccharide in mouse model infected via intranasal route of exposure
    Osman AY, Saharee AA, Jesse FF, Kadir AA
    Microb Pathog, 2017 Sep;110:365-374.
    PMID: 28710016 DOI: 10.1016/j.micpath.2017.07.014
    In this study, we developed a mouse model and characterized the effects of intranasal inoculation of virulent Brucella melitensis strain 16M and its lipopolysaccharide (LPS). The effects of the exposure were compared with respective control groups. Both Brucella melitensis-infected and LPS-infected groups showed no significant clinical presentation with minor relevance in the mortality associated with the infection. In Brucella melitensis-infected group, significant histopathological changes in comparison to the LPS infected group with increase bacterial burden in the lungs, reproductive and reticuloendothelial organs were observed. However, both infected groups showed elevated levels of pro-inflammatory cytokine expression (IL-1β and IL6) and antibody production (IgM an IgG) as early as 3 days post-infection with predominance in LPS infected group. In contrast, low levels of sex related hormonal changes was recorded in both infected groups throughout the experimental period. This is the first detailed investigation comparing the infection progression and host responses in relation to the immunopathophysiological aspects in mouse model after intranasal inoculation with B. melitensis and its lipopolysaccharide. The study revealed a significant difference between infected and control groups with overlap in clinical, pathological, and immunological responses as well as sex related hormonal changes resulting from the infections.
    Matched MeSH terms: Liver/drug effects
  3. The ribosomal protein L19 mRNA is induced by copper exposure in the swordtail fish, Xiphophorus helleri
    Aliza D, Tey CL, Ismail IS, Kuah MK, Shu-Chien AC, Muhammad TS
    Mol Biol Rep, 2012 Apr;39(4):4823-9.
    PMID: 21956757 DOI: 10.1007/s11033-011-1275-3
    Teleosts are useful vertebrate model species for understanding copper toxicity due to the dual entry route for copper intake via the gills and intestine. In this present study, we utilized the differential display reverse transcription-polymerase chain reaction to isolate potential novel hepatic genes induced by sublethal copper exposure in the freshwater swordtail fish, Xiphophorus helleri. Full length cloning of a cDNA fragment induced by copper exposure to 1 μg/ml during 24 h resulted in the positive identification of a hepatic ribosomal protein L19 (RPL19) gene. Further characterization of this gene revealed that its transcriptional expression was dependent on dosage and time of copper exposure. This study describes for the first time the involvement of RPL19 in copper toxicity, probably as a result of increase in ribosome synthesis rate to support activities such as cellular protein translation, transcriptional activation and mRNA stabilization during sublethal copper exposure.
    Matched MeSH terms: Liver/drug effects
  4. Fulltext Phaleria macrocarpa Boerl. (Thymelaeaceae) leaves increase SR-BI expression and reduce cholesterol levels in rats fed a high cholesterol diet
    Andriani Y, Tengku-Muhammad TS, Mohamad H, Saidin J, Syamsumir DF, Chew GS, et al.
    Molecules, 2015 Mar 09;20(3):4410-29.
    PMID: 25759957 DOI: 10.3390/molecules20034410
    In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl (Thymelaeaceae) leaves against the therapeutic target for hypercholesterolemia were done using the HDL receptor (SR-BI) and hypercholesterolemia-induced Sprague Dawley rats. The in vitro study showed that the active fraction (CF6) obtained from the ethyl acetate extract (EMD) and its component 2',6',4-trihydroxy-4'-methoxybenzophenone increased the SR-BI expression by 95% and 60%, respectively. The in vivo study has proven the effect of EMD at 0.5 g/kgbw dosage in reducing the total cholesterol level by 224.9% and increasing the HDL cholesterol level by 157% compared to the cholesterol group. In the toxicity study, serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activity were observed to be at normal levels. The liver histology also proved no toxicity and abnormalities in any of the treatment groups, so it can be categorized as non-toxic to the rat liver. The findings taken together show that P. macrocarpa leaves are safe and suitable as an alternative control and prevention treatment for hypercholesterolemia in Sprague Dawley rats.
    Matched MeSH terms: Liver/drug effects
  5. Fulltext Ipomoea aquatica extract shows protective action against thioacetamide-induced hepatotoxicity
    Alkiyumi SS, Abdullah MA, Alrashdi AS, Salama SM, Abdelwahab SI, Hadi AH
    Molecules, 2012;17(5):6146-55.
    PMID: 22617138 DOI: 10.3390/molecules17056146
    In the Indian system of traditional medicine (Ayurveda) it is recommended to consume Ipomoea aquatica to mitigate disorders like jaundice. In this study, the protective effects of ethanol extract of I. aquatica against liver damage were evaluated in thioacetamide (TAA)-induced chronic hepatotoxicity in rats. There was no sign of toxicity in the acute toxicity study, in which Sprague-Dawley (SD) rats were orally fed with I. aquatica (250 and 500 mg/kg) for two months along with administration of TAA (i.p injection 200 mg/kg three times a week for two months). The results showed that the treatment of I. aquatica significantly lowered the TAA-induced serum levels of hepatic enzyme markers (ALP, ALT, AST, protein, albumin, bilirubin and prothrombin time). The hepatic content of activities and expressions SOD and CAT that were reduced by TAA were brought back to control levels by the plant extract supplement. Meanwhile, the rise in MDA level in the TAA receiving groups also were significantly reduced by I. aquatica treatment. Histopathology of hepatic tissues by H&E and Masson trichrome stains displayed that I. aquatica has reduced the incidence of liver lesions, including hepatic cells cloudy swelling, infiltration, hepatic necrosis, and fibrous connective tissue proliferation induced by TAA in rats. Therefore, the results of this study show that the protective effect of I. aquatica in TAA-induced liver damage might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects. Moreover, it confirms a scientific basis for the traditional use of I. aquatica for the treatment of liver disorders.
    Matched MeSH terms: Liver/drug effects
  6. Fulltext Moringa oleifera hydroethanolic extracts effectively alleviate acetaminophen-induced hepatotoxicity in experimental rats through their antioxidant nature
    Fakurazi S, Sharifudin SA, Arulselvan P
    Molecules, 2012 Jul 10;17(7):8334-50.
    PMID: 22781444 DOI: 10.3390/molecules17078334
    The aim of the study was to investigate the in vitro antioxidant properties Moringa oleifera Lam. (MO) extracts and its curative role in acetaminophen (APAP)-induced toxic liver injury in rats caused by oxidative damage. The total phenolic content and antioxidant properties of hydroethanolic extracts of different MO edible parts were investigated by employing an established in vitro biological assay. In the antihepatotoxic study, either flowers or leaves extract (200 mg/kg or 400 mg/kg, i.p) were administered an hour after APAP administration, respectively. N-Acetylcysteine was used as the positive control against APAP-induced hepatotoxicity. The levels of liver markers such as alanine aminotransferase (ALT) and the levels of oxidative damage markers including malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) protein adduct, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were analysed and compared between experimental groups. Among MO edible parts the flower extracts contain the highest total phenolic content and antioxidant capacity, followed by leaves extract. The oxidative marker MDA, as well as 4-HNE protein adduct levels were elevated and GSH, SOD and CAT were significantly decreased in groups treated with hepatotoxin. The biochemical liver tissue oxidative markers measured in the rats treated with MO flowers and leaves hydroethanolic extracts showed a significant (p < 0.05) reduction in the severity of the liver damage. The results of this study strongly indicate the therapeutic properties of MO hydroethanolic extracts against acute liver injury and thereby scientifically support its traditional use.
    Matched MeSH terms: Liver/drug effects*
  7. Fulltext Hepatoprotective potential of Clitoria ternatea leaf extract against paracetamol induced damage in mice
    Nithianantham K, Shyamala M, Chen Y, Latha LY, Jothy SL, Sasidharan S
    Molecules, 2011 Dec 06;16(12):10134-45.
    PMID: 22146374 DOI: 10.3390/molecules161210134
    BACKGROUND AND AIM: Clitoria ternatea, a medicinal herb native to tropical equatorial Asia, is commonly used in folk medicine to treat various diseases. The aim of the present study is to evaluate the hepatoprotective and antioxidant activity of C. ternatea against experimentally induced liver injury.

    METHODS: The antioxidant property of methanolic extract (ME) of C. ternatea leaf was investigated by employing an established in vitro antioxidant assay. The hepatoprotective effect against paracetamol-induced liver toxicity in mice of ME of C. ternatea leaf was also studied. Activity was measured by monitoring the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and billirubin along with histopathological analysis.

    RESULTS: The amount of total phenolics and flavonoids were estimated to be 358.99 ± 6.21 mg/g gallic acid equivalent and 123.75 ± 2.84 mg/g catechin equivalent, respectively. The antioxidant activity of C. ternatea leaf extract was 67.85% at a concentration of 1 mg/mL and was also concentration dependant, with an IC(50) value of 420.00 µg/mL. The results of the paracetamol-induced liver toxicity experiments showed that mice treated with the ME of C. ternatea leaf (200 mg/kg) showed a significant decrease in ALT, AST, and bilirubin levels, which were all elevated in the paracetamol group (p < 0.01). C. ternatea leaf extract therapy also protective effects against histopathological alterations. Histological studies supported the biochemical findings and a maximum improvement in the histoarchitecture was seen.

    CONCLUSIONS: The current study confirmed the hepatoprotective effect of C. ternatea leaf extract against the model hepatotoxicant paracetamol. The hepatoprotective action is likely related to its potent antioxidative activity.

    Matched MeSH terms: Liver/drug effects
  8. Fulltext Efficacy of carbazole alkaloids, essential oil and extract of Murraya koenigii in enhancing subcutaneous wound healing in rats
    Nagappan T, Segaran TC, Wahid ME, Ramasamy P, Vairappan CS
    Molecules, 2012 Dec 05;17(12):14449-63.
    PMID: 23519245 DOI: 10.3390/molecules171214449
    The traditional use of Murraya koenigii as Asian folk medicine prompted us to investigate its wound healing ability. Three carbazole alkaloids (mahanine (1), mahanimbicine (2), mahanimbine (3)), essential oil and ethanol extract of Murraya koenigii were investigated for their efficacy in healing subcutaneous wounds. Topical application of the three alkaloids, essential oil and crude extract on 8 mm wounds created on the dorsal skin of rats was monitored for 18 days. Wound contraction rate and epithelialization duration were calculated, while wound granulation and collagen deposition were evaluated via histological method. Wound contraction rates were obvious by day 4 for the group treated with extract (19.25%) and the group treated with mahanimbicine (2) (12.60%), while complete epithelialization was achieved on day 18 for all treatment groups. Wounds treated with mahanimbicine (2) (88.54%) and extract of M. koenigii (91.78%) showed the highest rate of collagen deposition with well-organized collagen bands, formation of fibroblasts, hair follicle buds and with reduced inflammatory cells compared to wounds treated with mahanine (1), mahanimbine (3) and essential oil. The study revealed the potential of mahanimbicine (2) and crude extract of M. koenigii in facilitation and acceleration of wound healing.
    Matched MeSH terms: Liver/drug effects
  9. Fulltext In vitro and in vivo effects of three different Mitragyna speciosa korth leaf extracts on phase II drug metabolizing enzymes--glutathione transferases (GSTs)
    Azizi J, Ismail S, Mordi MN, Ramanathan S, Said MI, Mansor SM
    Molecules, 2010 Jan 20;15(1):432-41.
    PMID: 20110902 DOI: 10.3390/molecules15010432
    In the present study, we investigate the effects of three different Mitragyna speciosa extracts, namely methanolic, aqueous and total alkaloid extracts, on glutathione transferase-specific activity in male Sprague Dawley rat liver cytosol in vitro and in vivo. In the in vitro study, the effect of Mitragyna speciosa extracts (0.01 to 750 microg/mL) against the specific activity of glutathione transferases was examined in rat liver cytosolic fraction from untreated rats. Our data show concentration dependent inhibition of cytosolic GSTs when Mitragyna speciosa extract was added into the reaction mixture. At the highest concentration used, the methanolic extract showed the highest GSTs specific activity inhibition (61%), followed by aqueous (50%) and total alkaloid extract (43%), respectively. In in vivo study, three different dosages; 50, 100 and 200 mg/kg for methanolic and aqueous extracts and 5, 10 and 20 mg/kg for total alkaloid extract were given orally for 14 days. An increase in GST specific activity was generally observed. However, only Mitragyna speciosa aqueous extract with a dosage of 100 mg/kg showed significant results: 129% compared to control.
    Matched MeSH terms: Liver/drug effects
  10. Fulltext Evaluation of the hepatoprotective Effects of Lantadene A, a pentacyclic triterpenoid of Lantana plants against acetaminophen-induced liver damage
    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
  11. Fulltext Hepatoprotective Effect of Supercritical Carbon Dioxide Extracted Dabai Pulp Oil and Its Defatted Pulp
    Kadir NAAA, Azlan A, Abas F, Ismail IS
    Molecules, 2021 Jan 28;26(3).
    PMID: 33525363 DOI: 10.3390/molecules26030671
    All food scientists must utilize plants for their application as functional foods to reduce hypercholesterolemia incidence through diet. Canarium odontophyllum (dabai) is a novel source for new healthy oil and functional foods. In this work, we evaluate the hepatoprotective effects of supercritical carbon dioxide (SC-CO2) extracted dabai pulp oil (DPO) and defatted dabai pulp (DDP) against hypercholesterolemia elicited by a high-cholesterol diet in rats. Our results show that DPO and DDP supplementation exerted beneficial hypocholesterolemic effects against the high-cholesterol diet-fed rat. Nevertheless, supplementation with DDP revealed superior total cholesterol, low-density lipoprotein, and HMG-CoA reductase lowering efficacy (p < 0.05). Supplementation of either DPO or DDP did not significantly affect AST and ALT levels than normal rats (p > 0.05). Therefore, DDP and DPO are considered as having no toxicological significance. The histological section of rats treated with DPO and DDP showed improved steatosis in hepatocytes. HPLC analysis revealed that DPO and DDP contained syringic acid, which plays an important role in the beneficial effect. In conclusion, our results support the hypocholesterolemic and hepatoprotective effects of DPO and DDP in the hypercholesterolemic rats model.
    Matched MeSH terms: Liver/drug effects*
  12. Fulltext Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents
    Abdullah NH, Ismail S
    Molecules, 2018 Oct 19;23(10).
    PMID: 30347696 DOI: 10.3390/molecules23102696
    The co-use of conventional drug and herbal medicines may lead to herb-drug interaction via modulation of drug-metabolizing enzymes (DMEs) by herbal constituents. UDP-glucuronosyltransferases (UGTs) catalyzing glucuronidation are the major metabolic enzymes of Phase II DMEs. The in vitro inhibitory effect of several herbal constituents on one of the most important UGT isoforms, UGT2B7, in human liver microsomes (HLM) and rat liver microsomes (RLM) was investigated. Zidovudine (ZDV) was used as the probe substrate to determine UGT2B7 activity. The intrinsic clearance (Vmax/Km) of ZDV in HLM is 1.65 µL/mg/min which is ten times greater than in RLM, which is 0.16 µL/mg/min. Andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone inhibited ZDV glucuronidation in HLM with IC50 values of 6.18 ± 1.27, 18.56 ± 8.62, 8.11 ± 4.48 and 4.57 ± 0.23 µM, respectively, hence, herb-drug interactions are possible if andrographolide, kaempferol-3-rutinoside, mitragynine and zerumbone are taken together with drugs that are highly metabolized by UGT2B7. Meanwhile, only mitragynine and zerumbone inhibited ZDV glucuronidation in RLM with IC50 values of 51.20 ± 5.95 μM and 8.14 ± 2.12 µM, respectively, indicating a difference between the human and rat microsomal model so caution must be exercised when extrapolating inhibitory metabolic data from rats to humans.
    Matched MeSH terms: Microsomes, Liver/drug effects*
  13. Fulltext In Vivo Toxicity Evaluation of Sugar Adulterated Heterotrigona itama Honey Using Zebrafish Model
    Fakhlaei R, Selamat J, Razis AFA, Sukor R, Ahmad S, Amani Babadi A, et al.
    Molecules, 2021 Oct 15;26(20).
    PMID: 34684803 DOI: 10.3390/molecules26206222
    Honey is prone to be adulterated through mixing with sugars, cheap and low-quality honey, and other adulterants. Consumption of adulterated honey may cause several health issues such as weight gain, diabetes, and liver and kidney dysfunction. Therefore, studying the impact of consumption of adulterated honey on consumers is critical since there is a lack of study in this field. Hence, the aims of this paper were: (1) to determine the lethal concentration (LC50) of adulterated honey using zebrafish embryo, (2) to elucidate toxicology of selected adulterated honey based on lethal dose (LD50) using adult zebrafish, (3) to determine the effects of adulterated honey on histological changes of zebrafish, and (4) to screen the metabolites profile of adulterated honey by using zebrafish blood serum. The LC50 of Heterotrigona itama honey (acacia honey) and its sugar adulterants (light corn sugar, cane sugar, inverted sugar, and palm sugar in the proportion of 1-3% (w/w) from the total volume) was determined by the toxicological assessment of honey samples on zebrafish embryos (different exposure concentrations in 24, 48, 72, and 96 h postfertilization (hpf)). Pure H. itama honey represents the LC50 of 34.40 ± 1.84 (mg/mL) at 96 hpf, while the inverted sugar represents the lowest LC50 (5.03 ± 0.92 mg/mL) among sugar adulterants. The highest concentration (3%) of sugar adulterants were used to study the toxicology of adulterated honey using adult zebrafish in terms of acute, prolong-acute, and sub-acute tests. The results of the LD50 from the sub-acute toxicity test of pure H. itama honey was 2.33 ± 0.24 (mg/mL). The histological studies of internal organs showed a lesion in the liver, kidney, and spleen of adulterated treated-honey groups compared to the control group. Furthermore, the LC-MS/MS results revealed three endogenous metabolites in both the pure and adulterated honey treated groups, as follows: (1) S-Cysteinosuccinic acid, (2) 2,3-Diphosphoglyceric acid, and (3) Cysteinyl-Tyrosine. The results of this study demonstrated that adulterated honey caused mortality, which contributes to higher toxicity, and also suggested that the zebrafish toxicity test could be a standard method for assessing the potential toxicity of other hazardous food additives. The information gained from this research will permit an evaluation of the potential risk associated with the consumption of adulterated compared to pure honey.
    Matched MeSH terms: Liver/drug effects
  14. Fulltext The combination of mitragynine and morphine prevents the development of morphine tolerance in mice
    Fakurazi S, Rahman SA, Hidayat MT, Ithnin H, Moklas MA, Arulselvan P
    Molecules, 2013 Jan 04;18(1):666-81.
    PMID: 23292329 DOI: 10.3390/molecules18010666
    Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.
    Matched MeSH terms: Liver/drug effects
  15. Fulltext Cytoprotective effect of benzyl N'-(5-chloro-indol-3-yl-methylidene)-hydrazinecarbodithioate against ethanol-induced gastric mucosal injury in rats
    Hashim H, Mughrabi FF, Ameen M, Khaledi H, Ali HM
    Molecules, 2012 Aug 03;17(8):9306-20.
    PMID: 22864239 DOI: 10.3390/molecules17089306
    Indolic compounds have attracted a lot of attention due to their interesting biological properties. The present study was performed to evaluate the subacute toxicity and anti-ulcer activity of BClHC against ethanol-induced gastric ulcers. Experimental animal groups were orally pre-treated with different doses of BClHC (50, 100, 200 and 400 mg/kg) in 10% Tween 20 solution (vehicle). Blank and ulcer control groups were pre-treated with vehicle. The positive group was orally pretreated with 20 mg/kg omeprazole. After one hour, all groups received absolute ethanol (5 mL/kg) to generate gastric mucosal injury except the blank control group which was administered the vehicle solution. After an additional hour, all rats were sacrificed, and the ulcer areas of the gastric walls determined. Grossly, the ulcer control group exhibited severe mucosal injury, whereas pre-treatment with either derivative or omeprazole resulted in significant protection of gastric mucosal injury. Flattening of gastric mucosal folds was also observed in rats pretreated with BClHC. Histological studies of the gastric wall of ulcer control group revealed severe damage of gastric mucosa, along with edema and leucocytes infiltration of the submucosal layer compared to rats pre-treated with either BClHC or omeprazole where there were marked gastric protection along with reduction or absence of edema and leucocytes infiltration of the submucosal layer. Subacute toxicity study with a higher dose of derivative (5 g/kg) did not manifest any toxicological signs in rats. In conclusions, the present finding suggests that benzyl N'-(5-chloroindol-3-ylmethylidene)hydrazinecarbodithioate promotes ulcer protection as ascertained by the comparative decreases in ulcer areas, reduction of edema and leucocytes infiltration of the submucosal layer.
    Matched MeSH terms: Liver/drug effects
  16. Antihyperglycaemic effects of ethanol extracts of Carica papaya and Pandanus amaryfollius leaf in streptozotocin-induced diabetic mice
    Sasidharan S, Sumathi V, Jegathambigai NR, Latha LY
    Nat Prod Res, 2011 Dec;25(20):1982-7.
    PMID: 21707251 DOI: 10.1080/14786419.2010.523703
    Diabetes mellitus is a global disease that is increasing in an alarming rate. The present study was undertaken to study the antidiabetic effect of the ethanol extracts of Carica papaya and Pandanus amaryfollius on streptozotocin-induced diabetic mice. The results of the present study indicated that there was no significant difference in the body weight of the treated groups when compared to diabetic control. Whereas, there was significant (P liver tissues of the treated group indicated a reduction in fatty changes and pyknotic nucleus. The kidney tissues of the treated groups indicated significant recovery in the cuboidal tissue. The results from the phytochemical screening indicated the presence of flavonoids, alkaloids, saponin and tannin in C. papaya and P. amaryfollius. The antidiabetic effect of C. papaya and P. amaryfollius observed in the present study may be due to the presence of these phytochemicals.
    Matched MeSH terms: Liver/drug effects
  17. Potential protective effect of sunitinib after administration of diclofenac: biochemical and histopathological drug-drug interaction assessment in a mouse model
    Tan JR, Chakravarthi S, Judson JP, Haleagrahara N, Segarra I
    Naunyn Schmiedebergs Arch Pharmacol, 2013 Jul;386(7):619-33.
    PMID: 23552887 DOI: 10.1007/s00210-013-0861-4
    Sunitinib is a tyrosine kinase inhibitor for GIST and advanced renal cell carcinoma. Diclofenac is used in cancer pain management. Coadministration may mediate P450 toxicity. We evaluate their interaction, assessing biomarkers ALT, AST, BUN, creatinine, and histopathological changes in the liver, kidney, heart, brain, and spleen. ICR mice (male, n = 6 per group/dose) were administered saline (group A) or 30 mg/kg diclofenac ip (group B), or sunitinib po at 25, 50, 80, 100, 140 mg/kg (group C) or combination of diclofenac (30 mg/kg, ip) and sunitinib (25, 50, 80, 100, 140 mg/kg po). Diclofenac was administered 15 min before sunitinib, mice were euthanized 4 h post-sunitinib dose, and biomarkers and tissue histopathology were assessed. AST was 92.2 ± 8.0 U/L in group A and 159.7 ± 14.6 U/L in group B (p < 0.05); in group C, it the range was 105.1-152.6 U/L, and in group D, it was 156.0-209.5 U/L (p < 0.05). ALT was 48.9 ± 1.6 U/L (group A), 95.1 ± 4.5 U/L (p < 0.05) in group B, and 50.5-77.5 U/L in group C and 82.3-115.6 U/L after coadministration (p < 0.05). Renal function biomarker BUN was 16.3 ± 0.6 mg/dl (group A) and increased to 29.9 ± 2.6 mg/dl in group B (p < 0.05) and it the range was 19.1-33.3 mg/dl (p < 0.05) and 26.9-40.8 mg/dl in groups C and D, respectively. Creatinine was 5.9 pmol/ml in group A; 6.2 pmol/ml in group B (p < 0.01), and the range was 6.0-6.2 and 6.2-6.4 pmol/ml in groups C and D, respectively (p < 0.05 for D). Histopathological assessment (vascular and inflammation damages) showed toxicity in group B (p < 0.05) and mild toxicity in group C. Damage was significantly lesser in group D than group B (p < 0.05). Spleen only showed toxicity after coadministration. These results suggest vascular and inflammation protective effects of sunitinib, not shown after biomarker analysis.
    Matched MeSH terms: Liver/drug effects
  18. Toxicological and pharmacokinetic analysis at therapeutic dose of SRS27, an investigational anti-asthma agent
    Lim JCW, Sagineedu SR, Yong ACH, Sidik SM, Wong WSF, Stanslas J
    Naunyn Schmiedebergs Arch Pharmacol, 2021 Jan;394(1):95-105.
    PMID: 32840650 DOI: 10.1007/s00210-020-01966-3
    SRS27, an andrographolide analogue, had been proven to have therapeutic properties at a dose of 3 mg/kg in both in vitro and in vivo asthma models of our previous study. The present study focuses on the pharmacokinetic and toxicity profile of this compound to provide further evidence for the development of this compound as an anti-asthma agent. A simple pharmacokinetic study was performed in female BALB/c mice to measure blood plasma concentration of the compound at therapeutic dose. At a single dose of 3 mg/kg, SRS27 had a relatively short half-life but was able to achieve a concentration range of 13-19 μM that is related to its in vitro bioactivities. With regard to toxicity profile, SRS27 appears to be safe, as no histopathological changes were observed in the liver, kidneys and ovaries of SRS27-treated female BALB/c mice. In addition, there was no significant change in the mean body weight and organ weight of the animals in the SRS27-treated groups compared with the vehicle-treated control group at the end of the treatment. This fully supports the absence of any significant changes in peripheral blood leukocyte counts of SRS27-treated mice. Rewardingly, this acute toxicity study also revealed that SRS27 has a wide therapeutic window as no toxicity symptoms were detected with a dose up to 60 mg/kg daily when tested for 14 days. These results provide strong justification for further investigation of SRS27 as a potential new anti-asthma agent.
    Matched MeSH terms: Liver/drug effects
  19. Fulltext Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague-Dawley Rats
    Al Zarzour RH, Ahmad M, Asmawi MZ, Kaur G, Saeed MAA, Al-Mansoub MA, et al.
    Nutrients, 2017 Jul 18;9(7).
    PMID: 28718838 DOI: 10.3390/nu9070766
    Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.
    Matched MeSH terms: Liver/drug effects
  20. Fulltext Aqueous Partition of Methanolic Extract of Dicranopteris linearis Leaves Protects against Liver Damage Induced by Paracetamol
    Zakaria ZA, Kamisan FH, Mohd Nasir N, Teh LK, Salleh MZ
    Nutrients, 2019 Dec 04;11(12).
    PMID: 31817058 DOI: 10.3390/nu11122945
    This study aimed to determine the antioxidant and hepatoprotective activities of semi-purified aqueous partition obtained from the methanol extract of Dicranopteris linearis (AQDL) leaves against paracetamol (PCM)-induced liver intoxication in rats. The test solutions, AQDL (50, 250, and 500 mg/kg), were administered orally to rats (n = 6) once daily for seven consecutive days followed by the hepatotoxicity induction using 3 g/kg PCM (p.o.). Blood was collected for serum biochemical parameters analysis while the liver was collected for histopathological examination and endogenous antioxidant enzymes analysis. AQDL was also subjected to antioxidant determination and phytochemical analysis. Results obtained show that AQDL possessed high total phenolic content (TPC) value and remarkable radical scavenging activities. AQDL also significantly (p < 0.05) reduced the liver weight/body weight (LW/BW) ratio or serum level of ALT, AST, and total bilirubin while significantly (p < 0.05) increase the level of superoxide dismutase (SOD) and catalase (CAT) without affecting the malondialdehyde (MDA) in the liver indicating its hepatoprotective effect. Phytoconstituents analyses showed only the presence of saponins and triterpenes, but lack of flavonoids. In conclusion, AQDL exerts hepatoprotective activity via its high antioxidant potential and ability to modulate the endogenous enzymatic antioxidant defense system possibly via the synergistic action of saponins and triterpenes.
    Matched MeSH terms: Liver/drug effects
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