Li Ling
Email Address
phcll@nus.edu.sg
Organizational Units
PHARMACOLOGY
dept
YONG LOO LIN SCH OF MEDICINE
faculty
14 results
Publication Search Results
Now showing 1 - 10 of 14
Publication The ABCG2 C421A polymorphism does not affect oral nitrofurantoin pharmacokinetics in healthy Chinese male subjects(2008) Adkison, K.K.; Vaidya, S.S.; Mehta, A.A.; Lee, D.Y.; Polli, J.W.; Lou, Y.; Koo, S.H.; Li, L.; Lee, E.J.D.; Gross, A.S.; PHARMACOLOGYPublication An overview of the biological significance of endogenous gases: New roles for old molecules(2007) Li, L.; Moore, P.K.; PHARMACOLOGYPublication Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative, on carrageenan-induced hindpaw oedema formation in the rat(2007) Sidhapuriwala, J.; Li, L.; Bhatia, M.; Moore, P.K.; Sparatore, A.; PHARMACOLOGYS-diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2-dithiole-3-thione-5-yl)-phenyl ester) is a novel derivative of diclofenac which, in vivo, undergoes enzymatic cleavage of its ester linkage to release hydrogen sulfide (H2S) along with the parent moiety, diclofenac. In this study the anti-inflammatory activity of S-diclofenac and diclofenac was studied in a carrageenan-evoked hindpaw oedema model in the rat. Drugs or vehicle were administered 3 h before carrageenan. Both drugs produced a dose-dependent anti-inflammatory effect in this model. However, S-diclofenac (ED30, 14.2 ± 0.6 μmol/kg) was more potent (P < 0.05) than diclofenac (ED30, 39.3 ± 1.4 μmol/kg) as an inhibitor both of hindpaw swelling and in reducing the carrageenan-evoked rise in hindpaw myeloperoxidase activity reflecting tissue neutrophil infiltration (ED50s of 12.0 ± 2.1 μmol/kg and 21.9 ± 2.0 μmol/kg). Intraplantar carrageenan injection also significantly (P < 0.05) increased hindpaw concentrations of prostaglandin E2 (PGE2), nitrite/nitrate and H2S synthesizing activity measured at 6 h. Both S-diclofenac and diclofenac pretreatment reduced the carrageenan-induced rise in hindpaw PGE2, nitrite/nitrate and H2S synthesizing activity. Whilst treatment with either drug produced similar inhibition of hindpaw PGE2 and H2S synthesizing activity - S-diclofenac more effectively reduced hindpaw nitrite/nitrate concentration than did diclofenac. It is proposed that the enhanced anti-inflammatory effect of S-diclofenac relates to its ability to release H2S at the inflamed site. These data provide evidence for an anti-inflammatory effect of H2S. © 2007 Elsevier B.V. All rights reserved.Publication MORPHOLIN-4-IUM 4 METHOXYPHENYL (MORPHOLINO) PHOSPHINODITHIOATE (GYY4137) AS A NOVEL VASODILATOR AGENT(2010-10-28) MOORE, PHILIP KEITH; TAN, CHOON-HONG; LI, LING; GUAN, YAN YI; PHARMACOLOGYThe invention is directed to a method of administering hydrogen sulfide (H.sub.2S) slowly and sustainably to an individual in need thereof comprising administering an effective amount of a compound represented by the following structural formula: ##STR00001## or a pharmaceutically acceptable salt thereof.Publication Effect of dietary purines on the pharmacokinetics of orally administered ribavirin(2009) Li, L.; Koo, S.H.; Limenta, L.M.G.; Han, L.; Lee, E.J.D.; Hashim, K.B.; Quek, H.H.; PHARMACOLOGYPublication Hydrogen sulfide-induces DNA damage and changes in apoptotic gene expression in human lung fibroblast cells(2007) Baskar, R.; Li, L.; Moore, P.K.; PHARMACOLOGYPublication Hydrogen sulphide: A novel endogenous gasotransmitter facilitates erectile function(2007) Srilatha, B.; Adaikan, P.G.; Li, L.; Moore, P.K.; PHARMACOLOGY; OBSTETRICS & GYNAECOLOGYPublication Oral sulfasalazine as a clinical BCRP probe substrate: Pharmacokinetic effects of genetic variation (C421A) and pantoprazole coadministration(2010) Adkison, K.K.; Vaidya, S.S.; Mehta, A.A.; Lee, D.Y.; Polli, J.W.; Humphreys, J.E.; Koo, S.H.; Li, L.; Lee, E.J.D.; Gross, A.S.; Lou, Y.; PHARMACOLOGYPublication A nociceptive-intensity-dependent role for hydrogen sulphide in the formalin model of persistent inflammatory pain(2008) Lee, A.T.-H.; Jitendrakumar, Shah J.; Khanna, S.; Li, L.; Cheng, Y.; Moore, P.K.; PHARMACOLOGY; MEDICINE; PHYSIOLOGYThe present study investigated the hypothesis that hydrogen sulfide (H2S) is pro-nociceptive in the formalin model of persistent inflammatory pain in the adult rat. Hind paw injection of formalin evoked a concentration-dependent increase in the hind paw concentration of H2S. Increased concentration of H2S was found in homogenates prepared from hind paws injected with 5% (but not 1.25%) formalin. Correspondingly, animal nociceptive flinching and hind paw edema were maximal with 5% formalin. Both nociceptive flinching and hind paw edema induced by injection of 5% formalin were attenuated by pretreatment with dl-propargylglycine (PPG; 50 mg/kg, i.p.) which is an inhibitor of the H2S synthesizing enzyme cystathionine-γ-lyase (CSE). The effect of pretreatment with PPG was selective and the drug did not influence animal behavior or hind-paw edema with injection of 1.25% formalin. Furthermore, PPG pretreatment attenuated the induction of c-Fos in spinal laminae I-II following injection of 5% formalin. In contrast, co-injection of 1.25% formalin with sodium hydrogen sulfide (NaHS; 1 nmol/0.1 ml), a H2S donor, into the hind paw increased animal nociceptive behavior. Collectively, these findings show that the effect of peripheral H2S in the pathogenesis of inflammatory pain depends, at least in part, on the nociceptive intensity level. © 2008 IBRO.Publication Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative(2007) Li, L.; fLee, L.C.; Moore, P.K.; Rossoni, G.; Sparatore, A.; Del, Soldato P.; PHARMACOLOGYS-diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester; ACS 15) is a novel molecule comprising a hydrogen sulfide (H2S)-releasing dithiol-thione moiety attached by an ester linkage to diclofenac. S-diclofenac administration inhibited lipopolysaccharide-induced inflammation (as evidenced by reduced lung and liver myeloperoxidase activity) and caused significantly less gastric toxicity than diclofenac. S-diclofenac did not affect blood pressure or heart rate of the anesthetized rat. S-diclofenac administration downregulated expression of genes encoding enzymes which synthesize nitric oxide, prostanoids, and H2S; reduced plasma IL-1β/TNF-α; and elevated plasma IL-10. Reduced liver NF-κB p65 and AP-1/c-fos DNA-binding activity was also observed. These effects were mimicked in large part by a combination of diclofenac plus an H2S-releasing moiety (ADT-OH). Incubation of S-diclofenac (100 μM) with rat plasma or liver homogenate caused a time-dependent release of H2S, which was inhibited by sodium fluoride (10 mM). Administration of S-diclofenac (47.2 μmol/kg, ip) to conscious rats significantly increased plasma H2S concentration (at 45 min and 6 h). We propose that H2S release from S-diclofenac in vivo contributes to the observed effects. © 2007 Elsevier Inc. All rights reserved.