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  1. Zakaria ZA, Abdul Ghani ZD, Raden Mohd Nor RN, Gopalan HK, Sulaiman MR, Abdullah FC
    Yakugaku Zasshi, 2006 Nov;126(11):1197-203.
    PMID: 17077622
    The present study was carried out to establish the antinociceptive and anti-inflammatory properties of Dicranopteris linearis leaves chloroform extract in experimental animals. The antinociceptive activity was measured using the abdominal constriction, formalin and hot plate tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by evaporation under vacuo (40 degrees C) to dryness, was dissolved in dimethyl sulfoxide to the doses of 20, 100 and 200 mg/kg and administered subcutaneously 30 min prior to subjection to the above mentioned assays. The extract, at all doses used, was found to exhibit significant (p<0.05) antinociceptive activity in a dose-dependent manner. However, the significant (p<0.05) anti-inflammatory activity observed occur in a dose-independent manner. As a conclusion, the chloroform extract of D. linearis possesses antinociceptive and anti-inflammatory activity and thus justify its traditional uses by the Malays to treat various ailments.
    Matched MeSH terms: Dose-Response Relationship, Drug
  2. Zakaria ZA, Gopalan HK, Zainal H, Mohd Pojan NH, Morsid NA, Aris A, et al.
    Yakugaku Zasshi, 2006 Nov;126(11):1171-8.
    PMID: 17077618
    AIM: The present study was carried out to evaluate the antinociceptive, anti-inflammatory and antipyretic effects of chloroform extract of Solanum nigrum leaves using various animal models.

    METHODS: The extract was prepared by soaking (1:20; w/v) the air-dried powdered leaves (20 g) in chloroform for 72 hrs followed by evaporation (40 degrees C) under reduced pressure to dryness (1.26 g) and then dissolved (1:50; w/v) in dimethylsulfoxide (DMSO). The supernatant, considered as the stock solution with dose of 200 mg/kg, was diluted using DMSO to 20 and 100 mg/kg, and all doses were administered (s.c.; 10 ml/kg) in mice/rats 30 min prior to tests.

    RESULTS: The extract exhibited significant (p<0.05) antinociceptive activity when assessed using the abdominal constriction, hot plate and formalin tests. The extract also produced significant (p<0.05) anti-inflammatory and antipyretic activities when assessed using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests. Overall, the activities occurred in a dose-independent manner.

    CONCLUSION: The present study demonstrated that the lipid-soluble extract of S. nigrum leaves possessed antinociceptive, anti-inflammatory and anti-pyretic properties and confirmed the traditional claims.

    Matched MeSH terms: Dose-Response Relationship, Drug
  3. Jaganathan SK, Supriyanto E, Mandal M
    World J Gastroenterol, 2013 Nov 21;19(43):7726-34.
    PMID: 24282361 DOI: 10.3748/wjg.v19.i43.7726
    AIM: To investigate the events associated with the apoptotic effect of p-Coumaric acid, one of the phenolic components of honey, in human colorectal carcinoma (HCT-15) cells.

    METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium-bromide assay was performed to determine the antiproliferative effect of p-Coumaric acid against colon cancer cells. Colony forming assay was conducted to quantify the colony inhibition in HCT 15 and HT 29 colon cancer cells after p-Coumaric acid treatment. Propidium Iodide staining of the HCT 15 cells using flow cytometry was done to study the changes in the cell cycle of treated cells. Identification of apoptosis was done using scanning electron microscope and photomicrograph evaluation of HCT 15 cells after exposing to p-Coumaric acid. Levels of reactive oxygen species (ROS) of HCT 15 cells exposed to p-Coumaric acid was evaluated using 2', 7'-dichlorfluorescein-diacetate. Mitochondrial membrane potential of HCT-15 was assessed using rhodamine-123 with the help of flow cytometry. Lipid layer breaks associated with p-Coumaric acid treatment was quantified using the dye merocyanine 540. Apoptosis was confirmed and quantified using flow cytometric analysis of HCT 15 cells subjected to p-Coumaric acid treatment after staining with YO-PRO-1.

    RESULTS: Antiproliferative test showed p-Coumaric acid has an inhibitory effect on HCT 15 and HT 29 cells with an IC₅₀ (concentration for 50% inhibition) value of 1400 and 1600 μmol/L respectively. Colony forming assay revealed the time-dependent inhibition of HCT 15 and HT 29 cells subjected to p-Coumaric acid treatment. Propidium iodide staining of treated HCT 15 cells showed increasing accumulation of apoptotic cells (37.45 ± 1.98 vs 1.07 ± 1.01) at sub-G1 phase of the cell cycle after p-Coumaric acid treatment. HCT-15 cells observed with photomicrograph and scanning electron microscope showed the signs of apoptosis like blebbing and shrinkage after p-Coumaric acid exposure. Evaluation of the lipid layer showed increasing lipid layer breaks was associated with the growth inhibition of p-Coumaric acid. A fall in mitochondrial membrane potential and increasing ROS generation was observed in the p-Coumaric acid treated cells. Further apoptosis evaluated by YO-PRO-1 staining also showed the time-dependent increase of apoptotic cells after treatment.

    CONCLUSION: These results depicted that p-Coumaric acid inhibited the growth of colon cancer cells by inducing apoptosis through ROS-mitochondrial pathway.

    Matched MeSH terms: Dose-Response Relationship, Drug
  4. Abdul Ahmad SA, Palanisamy UD, Tejo BA, Chew MF, Tham HW, Syed Hassan S
    Virol J, 2017 11 21;14(1):229.
    PMID: 29162124 DOI: 10.1186/s12985-017-0895-1
    BACKGROUND: The rapid rise and spread in dengue cases, together with the unavailability of safe vaccines and effective antiviral drugs, warrant the need to discover and develop novel anti-dengue treatments. In this study the antiviral activity of geraniin, extracted from the rind of Nephelium lappaceum, against dengue virus type-2 (DENV-2) was investigated.

    METHODS: Geraniin was prepared from Nephelium lappaceum rind by reverse phase C-18 column chromatography. Cytotoxicity of geraniin towards Vero cells was evaluated using MTT assay while IC50 value was determined by plaque reduction assay. The mode-of-action of geraniin was characterized using the virucidal, attachment, penetration and the time-of-addition assays'. Docking experiments with geraniin molecule and the DENV envelope (E) protein was also performed. Finally, recombinant E Domain III (rE-DIII) protein was produced to physiologically test the binding of geraniin to DENV-2 E-DIII protein, through ELISA competitive binding assay.

    RESULTS: Cytotoxicity assay confirmed that geraniin was not toxic to Vero cells, even at the highest concentration tested. The compound exhibited DENV-2 plaque formation inhibition, with an IC50 of 1.75 μM. We further revealed that geraniin reduced viral infectivity and inhibited DENV-2 from attaching to the cells but had little effect on its penetration. Geraniin was observed to be most effective when added at the early stage of DENV-2 infection. Docking experiments showed that geraniin binds to DENV E protein, specifically at the DIII region, while the ELISA competitive binding assay confirmed geraniin's interaction with rE-DIII with high affinity.

    CONCLUSIONS: Geraniin from the rind of Nephelium lappaceum has antiviral activity against DENV-2. It is postulated that the compound inhibits viral attachment by binding to the E-DIII protein and interferes with the initial cell-virus interaction. Our results demonstrate that geraniin has the potential to be developed into an effective antiviral treatment, particularly for early phase dengue viral infection.

    Matched MeSH terms: Dose-Response Relationship, Drug
  5. Adam A, Marzuki A, Abdul Rahman H, Abdul Aziz M
    Vet Hum Toxicol, 1997 Jun;39(3):147-51.
    PMID: 9167243
    The toxicities of ROUNDUP and its component chemicals, glyphosate (N-phosphonomethylglycine) and polyoxyethyleneamine (POEA), were determined at 0, 1, 3, 6 and 24 h following administration to rats. The intratracheal administration of glyphosate (0.2 g/kg), POEA (0.1 g/kg), a mixture of glyphosate (0.2 g/kg) + POEA (0.1 g/kg), or ROUNDUP (containing 0.2 g/kg glyphosate and 0.1 g/kg POEA) elicited immediate respiratory effects which were more severe and which lasted longer in the groups receiving the POEA-containing preparations than in the glyphosate alone group. By 1 h, all test preparations had caused deaths, but more occurred from the POEA-containing preparations than from glyphosate. The po administration of POEA (1 g/kg), the mixture of glyphosate (2 g/kg) +POEA (1 g/kg), or ROUNDUP (containing 2 g/kg glyphosate and 1 g/kg POEA) produced diarrhea and blood-stained weeping from noses. Death was only seen from POEA at 24 h. Glyphosate (2 g/kg po) produced transient diarrhea without nose bleeds; POEA caused diarrhea at 1 h; and the mixture of POEA + glyphosate produced diarrhea later that increased in severity with time. Bloody nose secretions were seen only with the preparations that contained POEA. No deaths, respiratory effects or bloody nose secretions occurred in controls given saline. Both POEA and glyphosate caused lung hemorrhages and lung epithelial cell damage with po or intratracheal exposures. These results indicate POEA and preparations that contained POEA were more toxic than glyphosate.
    Matched MeSH terms: Dose-Response Relationship, Drug
  6. Loh WM, Ling WC, Murugan DD, Lau YS, Achike FI, Vanhoutte PM, et al.
    Vascul. Pharmacol., 2015 Aug;71:151-8.
    PMID: 25869508 DOI: 10.1016/j.vph.2015.03.011
    Des-aspartate angiotensin I (DAA-I), an endogenous nonapeptide, counteracts several effects of angiotensin II on vascular tone. The aim of this study was to investigate the acute protective effect of DAA-I on endothelial function in the spontaneously hypertensive rat (SHR) as well as its effect on angiotensin II-induced contractions and oxidative stress. Aortic rings were incubated with DAA-I (0.1μM) for 30min prior to the assessment of angiotensin II-induced contractions (0.1nM-10μM) in WKY and SHR aortas. Total nitrate and nitrite levels were assessed using a colorimetric method and reactive oxygen species (ROS) were measured by dihydroethidium (DHE) fluorescence and lucigenin-enhanced chemiluminescence. The effect of DAA-I was also assessed against endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside, respectively. Angiotensin II-induced contractions were significantly reduced by DAA-I, losartan and tempol. Incubation with ODQ (soluble guanylyl cyclase inhibitor) and removal of the endothelium prevented the reduction of angiotensin II-induced contractions by DAA-I. Total nitrate and nitrite levels were increased in DAA-I, losartan and tempol treated-SHR tissues while ROS level was reduced by DAA-I and the latter inhibitors. In addition, DAA-I significantly improved the impaired acetylcholine-induced relaxation in SHR aortas whilst sodium nitroprusside-induced endothelium-independent relaxation remained unaffected. The present findings indicate that improvement of endothelial function by DAA-I in the SHR aorta is mediated through endothelium-dependent release of nitric oxide and inhibition of angiotensin II-induced oxidative stress.
    Matched MeSH terms: Dose-Response Relationship, Drug
  7. Chin LC, Achike FI, Mustafa MR
    Vascul. Pharmacol., 2007 Mar;46(3):223-8.
    PMID: 17126611 DOI: 10.1016/j.vph.2006.10.005
    Hydrogen peroxide (H(2)O(2)) contributes in the regulation of vascular tone, especially in pathological states. The role of H(2)O(2) and superoxide anion free radicals in angiotensin II (Ang II)-induced contraction of diabetic tissues was examined with the aim of elucidating the underlying mechanisms. Isometric tension in response to various drug treatments was measured in isolated superior mesenteric arteries of streptozotocin (STZ)-induced diabetic WKY rats using the Mulvany wire myograph. Compared to the normal (euglycaemic) arteries, the Ang II-induced contraction was significantly reduced in diabetic arteries. Superoxide dismutase (SOD; converts superoxide to H(2)O(2)) significantly reduced the contraction in both types of arteries -- an effect abolished by catalase (H(2)O(2) scavenger), suggesting that the SOD effect was mediated by H(2)O(2). Treatment with catalase had no effect on the Ang II contraction in euglycaemic arteries, but it raised the contraction in diabetic arteries to euglycaemic levels. This increase was similar to that observed with diabetic arteries incubated with L-NAME. Combined catalase and L-NAME treatment further enhanced the contraction in diabetic arteries, suggesting that the catalase effect was not mediated by nitric oxide (NO). The catalase effect was abolished by indomethacin treatment. These results suggest that attenuation of Ang II-induced contraction in diabetic tissues is modulated by endogenous H(2)O(2), the scavenging of which unmasks an indomethacin-sensitive (and therefore cyclooxygenase product-mediated) Ang II-induced contraction.
    Matched MeSH terms: Dose-Response Relationship, Drug
  8. Chua YA, Abdullah WZ, Yusof Z, Gan SH
    Turk J Med Sci, 2015;45(4):913-8.
    PMID: 26422867
    BACKGROUND/AIM: VKORC1 and CYP2C9 genetic polymorphisms may not accurately predict warfarin dose requirements. We evaluated an existing warfarin dosing algorithm developed for Malaysian patients that was based only on VKORC1 and CYP2C9 genes.

    MATERIALS AND METHODS: Five Malay patients receiving warfarin maintenance therapy were investigated for their CYP2C9*2, CYP2C9*3, and VKORC1-1639G>A genotypes and their vitamin K-dependent (VKD) clotting factor activities. The records of their daily warfarin doses and international normalized ratio (INR) 2 years prior to and after the measurement of VKD clotting factors activities were acquired. The mean warfarin doses were compared with predicted warfarin doses calculated from a genotypic-based dosing model developed for Asians.

    RESULTS: A patient with the VKORC1-1639 GA genotype, who was supposed to have higher dose requirements, had a lower mean warfarin dose similar to those having the VKORC1-1639 AA genotype. This discrepancy may be due to the coadministration of celecoxib, which has the potential to decrease warfarins metabolism. Not all patients' predicted mean warfarin doses based on a previously developed dosing algorithm for Asians were similar to the actual mean warfarin dose, with the worst predicted dose being 54.34% higher than the required warfarin dose.

    CONCLUSION: Multiple clinical factors can significantly change the actual required dose from the predicted dose from time to time. The additions of other dynamic variables, especially INR, VKD clotting factors, and concomitant drug use, into the dosing model are important in order to improve its accuracy.

    Matched MeSH terms: Dose-Response Relationship, Drug
  9. Chin JH, Abas HH, Sabariah I
    Trop Biomed, 2008 Apr;25(1):9-16.
    PMID: 18600199
    Orthosiphon stamineus Benth (Family: Lamiaceae) or locally known as Misai Kucing has been widely used in Malaysia for treating kidney problems, gout, and diabetes. This study aims to evaluate the possible toxic effect after following fourteen days oral administration of methanol extract of O. stamineus in female Sprague Dawley (SD) rats. Control groups were treated orally with distilled water (vehicle) while the four test groups were treated up to fourteen days with 0.5 g/kg, 1 g/kg, 3 g/kg and 5 g/kg body weight of methanol extract of O. stamineus respectively. Toxicity of the methanol extract of O. stamineus was evaluated by the incident of lethality, side-cage observation and blood serum biochemical parameters. No lethality or adverse toxic signs were seen during the experimental period. A significant decrease in several serum biochemical parameters i.e. AST and ALT and increase in liver weight was observed in young female SD rat after being fed fourteen days with methanol extract of O. stamineus. No delayed toxic effect and lethality was observed in all rats during fourteen days of recovery period. In conclusion, methanol extract of O. stamineus within these range and treatment duration would not cause any severe toxic effects and organ damages in rats.
    Matched MeSH terms: Dose-Response Relationship, Drug
  10. Mohd Ridzuan MA, Ruenruetai U, Noor Rain A, Khozirah S, Zakiah I
    Trop Biomed, 2006 Dec;23(2):140-6.
    PMID: 17322815 MyJurnal
    Malaria is a disease which is still endemic and has become a disastrous scourge because of the emergence of antimalarial drug resistant Plasmodium falciparum. A new approach in addressing this is in developing a combination drug. This study is to show the enhancement of antimalarial properties, when single compound, goniothalamin combine with standard drug, chloroquine. Based on 4 Day Test, percentage of parasite growth on treated infected mice were determined. Oral treatment with 1 mg/kg BW of chloroquine on experimental mice suppressed 70% and 76.7% of both Plasmodium yoelii and Plasmodium berghei, respectively. The infection of P. berghei in mice was inhibited less than 50% by goniothalamin individual treatment at all doses in this study. About 27.8% and 18.5% inhibition of infection were observed in P. yoelii infected mice treated with 30 mg/kg and 60 mg/kg of goniothalamin respectively and the suppression exceed more than 50% at higher doses (90 and 120 mg/kg). Combination of 1 mg/kg chloroquine with either 30 mg/kg or 60 mg/kg of goniothalamin decreased the parasitemia of P. yoelii infected mice more than 90% and prolong the survival up to 100% after treatment. Similar treatment to P. berghei infected mice only shows about 60% reduction of parasitemia. The study findings showed that antimalarial property of goniothalamin was enhanced by combination with chloroquine at lower dose of each drug.
    Matched MeSH terms: Dose-Response Relationship, Drug
  11. Zaizuhana S, Puteri J Noor MB, Noral'ashikin Y, Muhammad H, Rohana AB, Zakiah I
    Trop Biomed, 2006 Dec;23(2):214-9.
    PMID: 17322824 MyJurnal
    Kacip Fatimah also known as Labisia pumila (Myrsinaceae), is a traditional herbal medicine with a long history in the Malay community. It has been used by many generations of Malay women to induce and facilitate childbirth as well as a post-partum medicine. We tested the genotoxic potential of Kacip Fatimah in bone marrow cells obtained from Sprague-Dawley rats using micronuclei formation as the toxicological endpoints. Five groups of five male rats each were administered orally for two consecutive days with doses of 100, 700 and 2000 mg/kg body weight of Kacip Fatimah extract dissolved in distilled water. Micronucleus preparation was obtained from bone marrow cells of the animals following standard protocols. No statistically significant increase in micronucleated polychromatic erythrocytes (MNPCEs) was observed at any dose level and sacrifice/harvest time point (24, 48 and 72h). However, a significant decrease in polychromatic erythrocytes/normochromatic erythrocytes (PCE:NCE) ratio was observed from the highest dose level (2000 mg/kg of body weight) at 48h harvest time point. In this study, we investigated the effect of Kacip Fatimah on mammalian bone marrow cells using micronuclei formation to assess the genotoxicity of the herb.
    Matched MeSH terms: Dose-Response Relationship, Drug
  12. Butt MA, Bhatti JA, Khalique A, Shahid MQ
    Trop Anim Health Prod, 2019 Nov;51(8):2595-2601.
    PMID: 31230253 DOI: 10.1007/s11250-019-01976-1
    The objective of current study was to determine the effect of fat supplement on physiological and reproductive performance of Holstein Friesian bulls during subtropical summer in Pakistan. Eighteen bulls were randomly divided into 3 treatment groups: (1) CTL, basal diet without fat supplementation; (2) FS100, basal diet with 100 g fat supplementation (Energizer-RP-10®, IFFCO, Johor, Malaysia); (3) FS200, basal diet with 200 g fat supplementation. Basal diet consisted of 50% green fodder (corn silage), 25% wheat straw, and 25% concentrate on dry matter basis. Diets were offered for 14 weeks from May to August 2016. The average daily temperature-humidity index ranged from 85 to 88 for the experimental period. The results indicated that there was no difference in dry matter intake, water intake, rectal temperature, pulse rate, and respiration rate among the treatment groups. Fat supplementation did not influence semen traits including sperm motility, progressive motility, amplitude of lateral head displacement, live-to-dead ratio, normal acrosomal ridge, plasma membrane integrity, and DNA integrity. The interaction of season with fat revealed that FA200 significantly increased post thaw semen motility and progressive motility during hot humid summer (P 
    Matched MeSH terms: Dose-Response Relationship, Drug
  13. Wong HS, Morad Z
    Transplant Proc, 2003 Feb;35(1):230-1.
    PMID: 12591376
    Matched MeSH terms: Dose-Response Relationship, Drug
  14. Choong CL, Wong HS, Lee FY, Lee CK, Kho JV, Lai YX, et al.
    Transplant Proc, 2018 Oct;50(8):2515-2520.
    PMID: 30316389 DOI: 10.1016/j.transproceed.2018.04.024
    BACKGROUND: Inhibition of calcineurin inhibitor (CNI) metabolism with diltiazem reduces the dose of tacrolimus required to achieve its therapeutic blood concentration in kidney transplant recipients (KTRs). This cost-savings maneuver is practiced in several countries, including Malaysia, but the actual impacts of diltiazem on tacrolimus blood concentration, dose-response relationship, cost-savings, and safety aspects are unknown.

    METHODS: This retrospective study was performed on all KTRs ≥18 years of age at our center from January 1, 2006 to December 31, 2015, who were prescribed diltiazem as tacrolimus-sparing agent. Blood tacrolimus trough level (TacC0) and other relevant clinical data for 70 eligible KTRs were reviewed.

    RESULTS: The dose of 1 mg tacrolimus resulted in a median TacC0 of 0.83 ± 0.52 ng/mL. With the introduction of a 90-mg/d dose diltiazem, there was a significant TacC0 increase to 1.39 ± 1.31 ng/mL/mg tacrolimus (P < .01). A further 90-mg increase in diltiazem to 180 mg/d resulted in a further increase of TacC0 to 1.66 ± 2.58 ng/mL/mg tacrolimus (P = .01). After this, despite a progressive increment of every 90-mg/d dose diltiazem to 270 mg/d and 360 mg/d, there was no further increment in TacC0 (1.44 ± 1.15 ng/mL/mg tacrolimus and 1.24 ± 0.94 ng/mL/mg tacrolimus, respectively [P < .01]). Addition of 180 mg/d diltiazem reduced the required tacrolimus dose to 4 mg/d, resulting in a cost-savings of USD 2045.92 per year (per patient) at our center. Adverse effects reported within 3 months of diltiazem introduction were bradycardia (1.4%) and postural hypotension (1.4%), which resolved after diltiazem dose reduction.

    CONCLUSION: Coadministration of tacrolimus and diltiazem in KTRs appeared to be safe and resulted in a TacC0 increment until reaching a 180-mg/d total diltiazem dose, at which point it began to decrease. This approach will result in a marked savings in immunosuppression costs among KTRs in Malaysia.

    Matched MeSH terms: Dose-Response Relationship, Drug
  15. Reichwaldt ES, Stone D, Barrington DJ, Sinang SC, Ghadouani A
    Toxins (Basel), 2016 08 31;8(9).
    PMID: 27589798 DOI: 10.3390/toxins8090251
    Alert level frameworks advise agencies on a sequence of monitoring and management actions, and are implemented so as to reduce the risk of the public coming into contact with hazardous substances. Their effectiveness relies on the detection of the hazard, but with many systems not receiving any regular monitoring, pollution events often go undetected. We developed toxicological risk assessment models for acute and chronic exposure to pollutants that incorporate the probabilities that the public will come into contact with undetected pollution events, to identify the level of risk a system poses in regards to the pollutant. As a proof of concept, we successfully demonstrated that the models could be applied to determine probabilities of acute and chronic illness types related to recreational activities in waterbodies containing cyanotoxins. Using the acute model, we identified lakes that present a 'high' risk to develop Day Away From Work illness, and lakes that present a 'low' or 'medium' risk to develop First Aid Cases when used for swimming. The developed risk models succeeded in categorising lakes according to their risk level to the public in an objective way. Modelling by how much the probability of public exposure has to decrease to lower the risks to acceptable levels will enable authorities to identify suitable control measures and monitoring strategies. We suggest broadening the application of these models to other contaminants.
    Matched MeSH terms: Dose-Response Relationship, Drug
  16. Mustafa MR
    Toxicon, 1993 Jan;31(1):67-74.
    PMID: 8446965
    The effect of the total glysosidic extract of the plant Sarcolobus globosus was investigated on the contractions of the smooth muscle of the guinea-pig ileal longitudinal muscle and taenia coli. In the ileal longitudinal muscle, addition of the extract inhibited the electrical field-stimulated twitches. Similarly to verapamil, it also reduced the contractions of the muscle to acetylcholine, histamine and KCl. However, only the tonic contraction to KCl was reversed by increasing the extracellular calcium concentration. In the taenia coli, lower concentrations of both the extract and verapamil induced a parallel displacement of the dose-response curves to calcium (0.30-30 mM). Addition of the extract also dose-dependently inhibited the KCl-induced contraction of the taenia coli. Increasing the calcium concentration increased the IC50 values of the extract. The result suggests that the inhibitory effect of the Sarcolobus globosus extract on the smooth muscle, like verapamil, is mainly due to inhibition of calcium influx.
    Matched MeSH terms: Dose-Response Relationship, Drug
  17. Koriem KM, Fathi GE, Salem HA, Akram NH, Gamil SA
    Toxicol. Mech. Methods, 2013 May;23(4):263-72.
    PMID: 23193971 DOI: 10.3109/15376516.2012.748857
    Cadmium has been classified as an environmental pollutant and human carcinogen. Pectin is a family of complex polysaccharides that function as hydrating agents and cementing materials for the cellulosic network. The aim of this study was to evaluate the protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats. Forty male Wistar rats were divided into five equal groups. Groups 1 and 2 were injected intraperitoneally (i.p.) saline (1 mg/kg) and pectin (50 mg/kg), respectively, two days/weeks over three weeks period. Groups 3-5 were injected i.p. with 1 mg/kg cadmium two days/week while groups 4 and 5 co-administrated i.p. with 25 and 50 mg/kg pectin, respectively, three days/week over three weeks period. The results of the present work revealed that cadmium-exposed rats showed decrease in serum testosterone, dehydroepiandrosterone sulfate and lactate dehydrogenase. Testicular cholesterol, total protein, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase and reduced glutathione levels were also decreased while testicular malondialdehyde level was increased after cadmium injection. On the other hand, serum luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and γ-glutamyl transpeptidase were increased after cadmium exposure. Cadmium also induced sperms loss. Co-administration of pectin with cadmium restores all the above parameters and sperms to the normal levels where pectin at higher dose was more effective than lower one. These results were supported by histochemical investigations. In conclusion, pectin can counteract the testicular toxicity and oxidative stress induced by cadmium and the effect was dose-dependent.
    Matched MeSH terms: Dose-Response Relationship, Drug
  18. Nisha AR, Hazilawati H, Mohd Azmi ML, Noordin MM
    Toxicol. Mech. Methods, 2017 Mar;27(3):215-222.
    PMID: 28030985 DOI: 10.1080/15376516.2016.1273432
    Polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants and chemically a class of structurally similar chemical compounds characterized by the presence of fused aromatic rings. This research was undertaken to find out immunotoxic effects produced by pyrene, phenanthrene and fluoranthene. These chemicals were injected into developing chicks at three dose levels (0.2, 2 and 20 mg per kg) through allantioc route to rule out possible mechanisms involved in immunotoxicity. DNA adduct produced by PAHs in immune organs were analyzed by DNA adduct enzyme-linked immunosorbent assay (ELISA) kit and DNA damage was assessed by comet assay. A significant increase in the DNA adduct levels was found in thymus and bursa in 2 mg and 20 mg dose levels of pyrene, fluoranthene and phenanthrene treated groups, whereas those in spleen simulated the value of controls. Comet assay indicated that PAHs especially pyrene, fluoranthene and phenanthrene were capable of inducing increased level of comet parameters in thymus at all the dose levels. Bursa of Fabricius and spleen also showed a gradual rise in comet parameters corresponding to all dose levels, but the increase was more marked as in thymus. Thus, it can be concluded that DNA adducts produced by PAHs lead to single-strand breaks and reduced DNA repair, which ultimately begin a carcinogenic process. Hence, this experiment can be considered as a strong evidence of genotoxic potential of PAHs like pyrene, phenanthrene and fluoranthene in developing chicks.
    Matched MeSH terms: Dose-Response Relationship, Drug
  19. Liew K, Yong PV, Lim YM, Navaratnam V, Ho AS
    Toxicol In Vitro, 2014 Apr;28(3):335-9.
    PMID: 24291160 DOI: 10.1016/j.tiv.2013.11.008
    Metastasis contributes to the escalating mortality rate among cancer patients worldwide. The search for novel and more effective anti-metastatic agent is crucial owing to the lack of anticancer drugs that can successfully combat metastasis. Hence, this study aims to examine the effects of 2-Methoxy-1,4-Naphthoquinone (MNQ) towards the metastasis of MDA-MB-231 cells. In invasion assays, the number of cells permeating across a Matrigel barrier was found to be decreased in a dose-dependent manner upon treatment with MNQ (0-7.5 μM). In wound-healing migration assays, MNQ exhibited dose-dependent inhibition of cell migration in which significant reduction in the zone of closure was observed as compared to untreated controls. Furthermore, the proteolytic activity of a pivotal metastatic mediator, matrix metalloproteinase-9 (MMP-9) was also downregulated by MNQ as determined by gelatin zymography. This study reports for the first time, the ability of MNQ to inhibit the invasion and migration characteristics of a highly metastatic MDA-MB-231 cancer cell line.
    Matched MeSH terms: Dose-Response Relationship, Drug
  20. Ng WK, Yazan LS, Ismail M
    Toxicol In Vitro, 2011 Oct;25(7):1392-8.
    PMID: 21609759 DOI: 10.1016/j.tiv.2011.04.030
    Thymoquinone (TQ), the active constituent of Nigella sativa or black cumin exhibited cytotoxic effects in several cancer cell lines. In this study, the cytotoxicity of TQ in human cervical squamous carcinoma cells (SiHa) was investigated. TQ was cytotoxic towards SiHa cells with IC50 values of 10.67 ± 0.12 and 9.33 ± 0.19 μg/mL as determined by MTT assay and trypan blue dye exclusion test, respectively, after 72 h of incubation. TQ was more cytotoxic towards SiHa cells compared to cisplatin. Interestingly, TQ was less cytotoxic towards the normal cells (3T3-L1 and Vero). Cell cycle analysis performed by flowcytometer showed a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Apoptosis induction by TQ was further confirmed by Annexin V/PI and AO/PI staining. Significant elevation of p53 and down-regulation of the anti-apoptotic Bcl-2 protein was found in the treated cells, without any changes in the expression of the pro-apoptotic Bax protein. In conclusion, thymoquinone from N. sativa was more potent than cisplatin in elimination of SiHa cells via apoptosis with down-regulation of Bcl-2 protein.
    Matched MeSH terms: Dose-Response Relationship, Drug
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