Browsing by Author "Yupin Sanvarinda"
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- Publication17β-estradiol attenuates LPS-induced interleukin-8 production by human peripheral blood monocytes through estrogen receptor-αactivation(2010-11-01) Nipapan Malisorn; Noppawan P. Morales; Yupin Sanvarinda; Payong Wanikiat; Mahidol UniversityProper regulation of the immune response is essential for immune homeostasis. Several proinflammatory cytokines released from activated monocytes mediate inflammation, including interleukine-8 (IL-8) which recruits neutrophils to the site of inflammation. 17β-Estradiol (E2) has a direct role in the modulation of the innate immune function and mediates profound effects on immune function of the monocytes. The effects of 17β-E2 are mediated principally by two receptor subtypes, ER and ER; both are expressed in monocytes. The aim of this study was, therefore, to characterize the estrogen receptor subtypes that mediate the estrogen effects on LPS-activated IL-8 production by human peripheral blood monocytes. 17β-E2 and PPT attenuated the production of IL-8 by LPS-activated monocytes in a dose-dependent manner and these effects can be reversed by ICI182, 780. These results suggested a role of ER on the attenuating effect of 17β-E2 on IL-8 production by human peripheral blood monocytes. © 2010 Academic Journals.
- ItemAdrenergic-cholinergic interaction in rat heart : evidence from radioligand binding studies(Mahidol University. Mahidol University Library and Knowledge Center, 2023) Surin Plasen; Kampon Sriwatanakul; Jutamaad Satayavivad; Supeenun Unchern; Krongtong Yoovathaworn; Yupin SanvarindaAdrenergic-cholinergic interaction plays an important role in the control of cardiac functions in both normal and disease states. When both divisions of the autonomic nervous system are stimulated simultaneously, the cholinergic components predominate the adrenergic nervous system. This accentuated antagonism can be clearly demonstrated at the physiological level. In this thesis, the first attempt has been made to demonstrate this interaction at the receptor level by using radioligand binding studies and computer assisted weighted nonlinear least-square curve fitting analysis (LIGAND program). By using [3H](-)DHA as a ?-adrenergic radioligand, it was demonstrated that muscarinic cholinergic receptor agonist, pilocarpine (10(-)7-10(-5) M) decreased the affinity of high affinity binding site for isoproterenol. There was no effect on antagonistic competition with propranolol. Gpp(NH)p (10-610-4 M) decreased the affinity of the ?-adrenergic receptor for isoproterenol for both high and low affinity binding sites. The simultaneous incubation of pilocarpine and Gpp(NH)p resulted in a reversal in affinity for both high and low affinity binding sites similar to those obtained from the control curve. These results s?ggest that muscarinic cholinergic agonist can modulate ?-adrenergic agonist affinity and that the Gpp(NH)p reduction of ?-adrenergic agonist affinity may be reversed by muscarinic cholinergic occupancy. These data are the first study to support that modification of one type of receptor may influence the other one situated nearby. By using [3H](-)QNB as a muscarinic cholinergic radioligand, isoproterenol (10(-6)-10(-5) M) decreased the affinity of high affinity binding site for pilocarpine. Effect on antagonistic competition with atropine could not be demonstrated. Gpp(NH)p (10(-6)-10(-4)M)decreased the affinity of muscarinic receptor for pilocarpine for both high and low affinity binding sites. The simultaneous incubation of isoproterenol and Gpp(NH)p resulted in a further decrease in affinity for both high and low affinity agonist sites. These results s?ggested that ?-adrenergic and muscarinic cholinergic receptor in the heart have interdependent linkage and can modulate agonist binding affinity of each other. Concanavalin A (Con A) was used as a probe to study this type of interaction at cell membrane level. Preincubation with Con A 0.5 ?g/ml for 30 min had no effect on [3H](-)DHA and [3H](-)QNB binding. It can be implied that amplification of agonist-stimulated cAMP generation by Con A is not due to an increase in agonist receptor coupling. Islet-activating protein(IAP) was also used as a probe to explore whether this adrenergic-cholinergic interaction is related to cyclic nucleotide metabolism. In the presence of 10-4 M Gpp(NH)p, 10-5 M pilocarpine cannot reverse the effect of 10-4 M Gpp(NH)p. These results s?ggested that IAP exerts its effects on this interaction at GTP binding protein level by cancelling the effect of pilocarpine in reversing the guanine nucleotide induced decrease in affinity of ?-adrenergic receptor for isoproterenol. It can be concluded that the phenomenon of accentuated antagonism in the heart could be explained for the first time that binding affinity of adrenoceptor may be changed significantly when the cholinoceptor situated nearby are simultaneously activated and this effect may be mediated via GTP binding protein.
- ItemAlterations of cardiac cholinoceptor and adrenoceptor responses during benzodiazepines treatment and termination(Mahidol University. Mahidol University Library and Knowledge Center, 2023) Krittika Polratana; Jutamaad Satayavivad; Yupin Sanvarinda; Laddawan Karchot; Noppamars Wongwitdecha
- PublicationAlterations of striatal cholinergic receptors after lesioning of the substantia nigra(1998-08-01) Yupin Sanvarinda; Laddawan Phivthongngam; Piyarat Govitrapong; Mahidol UniversityDopamine deficiency syndrome is known to cause cholinergic hyperactivity. Therefore, it was hypothesized that the said phenomenon may be due to enhanced cholinergic receptor functions. In the present study we examined the changes in striatal dopaminergic and cholinergic receptors in unilateral substantia nigra lesioned rats that showed vigorous ipsilateral rotation (total turns > 300) in response to apomorphine (1 mg kg-1ip). [3H] Spiperone ([3H]-SP) and [3H]-quinuclidinyl benzilate ([3H]-QNB) bindings were performed in the striata of the lesioned animals. There was no significant difference in the dissociation equilibrium constant values (K(d)) between the lesioned and non-lesioned sides. However, a significant difference in the maximum receptor density (B(max) of both [3H]-SP and [3H]-QNB bindings was observed between the lesioned and non-lesioned sides. The B(max) of [3H]-SP binding was significantly decreased on the lesioned side, whereas the B(max) of the [3H]-QNB binding was significantly increased. These results support the hypothesis that deficiencies of the dopaminergic system cause overactivity of the cholinergic system in the striatum.
- ItemAn In Vitro model for the study of Fe-catalyzed oxidation of LDL(Mahidol University. Mahidol University Library and Knowledge Center, 1998) Kwanta Pitaknantakul; Udom Chantharaksri; Yupin Sanvarinda; Supeenun Unchern
- ItemApomorphine-induced rotation in the substantia nigra lesioned rat : relationship to changes in biogenic amine receptors(Mahidol University. Mahidol University Library and Knowledge Center, 2024) Laddawal Phivthongngam; Yupin Sanvarinda; Piyarat KlangkalyaThe relationship between the destruction of dopamine (DA) containing neurons, specific binding of [(3)H]-spiperone ([(3)]-SP), [(3)H]-quinclidynyl benzilate ([(3)H)-QNE) and ipsilateral rotation in response to apomorphine (1 mg/kg, IP) was studied in rats with unilateral electrolytic lesions (2 mA DC, 15 sec) of the substantia nigra. The lesioned animals with rotational behavior in response to apomorphine were classified into 3 groups according to the number of total turns. The [(3)H] - SP binging and [(3)H]-QNB binding to striatal membrane were carried out in both lesioned and nonlesioned side. It has been shown that in rate, group I (number of trunes < 10), group II (number of turns between 80-150) and group III (number of turns > 300), there are no significant different in the equilibrium dissociation constant values (K(,d) between the lesioned and nonlesioned side. However, the significant differences of the maximal receptor density (B(,MAX) of both [(3)H] -SP binding and [(3)H]-QNB binding between the two striatal sides were observed in group III animals. The B(,max) after [(3)H]-SP binding in the lesioned side is 357 ± 103 fmol/mg protein and in the nonlesioned side is 759 ± 119 fmol/mg protein, whereas in [(3)HO]-QNB binding the B(,max) in the lesioned side is 460.14 ± 26.56 fmol/mg protein and in the nonlesioned side is 371.71 + 16.9 fmol/mg protein. The results of the present study show that the number of dopamine receptor binding sites and muscarinic receptor binding sites are altered in the striatum of the rats with significant rotational behavior in response to apomorphine. Furthermore, the number of dopaminergic binding sites decrease, while the number of muscarinic receptor binding sites increase which indicates the reciprocal relationship between the function of dopaminergic and cholinergic systems in the striatum.
- ItemBehavioral and neurobiochemical effects of chronic exposure to low dose of paraquat in rats(Mahidol University. Mahidol University Library and Knowledge Center, 2023) Wandee Sirapat; Jutamaad Satayavivad; Udom Chantharaksri; Yupin SanvarindaThe neurotoxic effects of chronic exposure to subcutaneous administration of low dose of paraquat on the motor behaviors and the alterations of the neurotransmitter levels (dopamine, norepinephrine, 5-hydroxytryptamine and its metabolites, 5-hydroxyindoleacetic acid) in various brain regions of male, Wistar rats were studied. Subcutaneous administration of paraquat 1, 2 and 3 mg/kg, 5 days per week for 8 weeks altered the total ambulatory and stereotypic activities in 20 minutes recorded by the open-field test. These alterations were dose- and time-dependent. There were no other obvious toxic effects of paraquat observed. The rotational behaviors were determined in the paraquat-treated groups as compared to control. It was found that there was no alteration in this motor behavior. In addition, the levels of dopamine in both paraquat-treated and control were not significantly different. The chronic exposure to 3-mg/kg dose of paraquat results in the significant lower body weight, motor performance and the norepinephrine levels in the hypothalamus as compared to control. The less body weight in paraquat-treated group as compared to control group may be related to the decreases in norepinephrine levels in the hypothalamus, which was previously suggested to have some role in feeding control. Hypothalamus appeared to be the area, among various discrete brain areas, that paraquat can easily pass into the brain due to its insufficient blood-brain barrier. The results of this study indicated that chronic exposure to paraquat can induce the neurotoxic effects with no detectable dopaminergic damage in the striatum, and there may be some noradrenergic system disturbance in the hypothalamus. The open-field test is one of the most sensitive methods that can detect the adverse effects of paraquat at low doses. Further studies are needed to elucidate the specific sites and mechanisms of paraquat induced the decreases in motor behavioral activities.
- PublicationCaffeine potentiates methamphetamine-induced toxicity both in vitro and in vivo(2011-09-08) Theerin Sinchai; Surin Plasen; Yupin Sanvarinda; Yamaratee Jaisin; Piyarat Govitrapong; Noppawan Phumala Morales; Piyanee Ratanachamnong; Duangporn Plasen; Mahidol University; Srinakharinwirot UniversityYa-Ba, a combination of the two potent psychostimulants methamphetamine (METH) and caffeine (CAF), is commonly used by drug abusers in Thailand and neighboring countries. While the neurotoxic effects of METH are well documented, the toxicity of this combination is mostly unknown. This study aimed to elucidate the effects of this particular drug combination using both in vitro and in vivo models. We found that combined treatment of METH and CAF at individually non-toxic concentrations significantly decreased viability of human neuroblastoma SK-N-SH cells. The reduction in cell survival was accompanied by an increase in reactive oxygen species (ROS) formation and the Bax/Bcl-2 ratio. In vivo data showed tha t combined administration of METH and CAF increased the mortality rate of rats, with an increase in the level of thiobarbituric acid reactive substances (TBARS), the indicator of oxidative stress, in striatal tissues. The results indicate that caffeine potentiates the toxic effects of methamphetamine, possibly via a mechanism involving an increase in dopamine release and excess ROS generation. © 2011 Elsevier Ireland Ltd.
- PublicationCurcumin i mediates neuroprotective effect through attenuation of quinoprotein formation, p-p38 MAPK expression, and caspase-3 activation in 6-hydroxydopamine treated SH-SY5Y cells(2014-01-01) Benjawan Meesarapee; Anusorn Thampithak; Yamaratee Jaisin; Pimtip Sanvarinda; Apichart Suksamrarn; Patoomratana Tuchinda; Noppawan Phumala Morales; Yupin Sanvarinda; Mahidol University; Burapha University; Srinakharinwirot University; Ramkhamhaeng University6-Hydroxydopamine (6-OHDA) selectively enters dopaminergic neurons and undergoes auto-oxidation resulting in the generation of reactive oxygen species and dopamine quinones, subsequently leading to apoptosis. This mechanism mimics the pathogenesis of Parkinson's disease and has been used to induce experimental Parkinsonism in both in vitro and in vivo systems. In this study, we investigated the effects of curcumin I (diferuloylmethane) purified from Curcuma longa on quinoprotein production, phosphorylation of p38 MAPK (p-p38), and caspase-3 activation in 6-OHDA-treated SH-SY5Y dopaminergic cells. Pretreatment of SH-SY5Y with curcumin I at concentrations of 1, 5, 10, and 20 μM, significantly decreased the formation of quinoprotein and reduced the levels of p-p38 and cleaved caspase-3 in a dose-dependent manner. Moreover, the levels of the dopaminergic neuron marker, phospho-tyrosine hydroxylase (p-TH), were also dose-dependently increased upon treatment with curcumin I. Our results clearly demonstrated that curcumin I protects neurons against oxidative damage, as shown by attenuation of p-p38 expression, caspase-3-activation, and toxic quinoprotein formation, together with the restoration of p-TH levels. This study provides evidence for the therapeutic potential of curcumin I in the chemoprevention of oxidative stress-related neurodegeneration. Copyright © 2013 John Wiley & Sons, Ltd.
- PublicationCurcumin I protects the dopaminergic cell line SH-SY5Y from 6-hydroxydopamine-induced neurotoxicity through attenuation of p53-mediated apoptosis(2011-02-11) Yamaratee Jaisin; Anusorn Thampithak; Benjawan Meesarapee; Piyanee Ratanachamnong; Apichart Suksamrarn; Laddawal Phivthong-ngam; Noppawan Phumala-Morales; Sukumal Chongthammakun; Piyarat Govitrapong; Yupin Sanvarinda; Mahidol University; Burapha University; Ramkhamhaeng University; Srinakharinwirot UniversityOxidative stress (OS) plays a pivotal role in the pathogenesis of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a neurotoxin used to induce oxidative cell death of dopaminergic neurons in experimental models of PD. Curcumin I, or diferuloylmethane is a pure compound isolated from Curcuma longa Linn. that has been reported to have neuroprotective properties. The precise mechanism, however, remains unclear. This study aims to elucidate the mechanisms by which curcumin I exerts its effects, using 6-OHDA-induced neurotoxicity in the human dopaminergic cell line SH-SY5Y. In our experiments, pretreatment with curcumin I improved cell viability, and significantly reduced reactive oxygen species (ROS). Further investigations revealed a reduction of p53 phosphorylation and decrease of the Bax/Bcl-2 ratio, as measured by mRNA expression and protein level. Taken together, these findings indicate that curcumin I protects dopaminergic neurons from 6-OHDA-induced toxicity via the reduction of ROS production, and subsequent attenuation of p53 phosphorylation and reduction of the Bax/Bcl-2 ratio. © 2010 Elsevier Ireland Ltd.
- ItemEffect of imidazoline and non-imidazoline alpha-adrenergic agents on human platelet aggregation(Mahidol University. Mahidol University Library and Knowledge Center, 2001) Piyada Songsermsakul; Darawan Pinthong; Yupin Sanvarinda; Supeenun Unchern
- PublicationEffects of Curcuma comosa on the expression of atherosclerosis-related cytokine genes in rabbits fed a high-cholesterol diet(2011-04-12) Puttavee Charoenwanthanang; Somsong Lawanprasert; Laddawal Phivthong-Ngam; Pawinee Piyachaturawat; Yupin Sanvarinda; Sureerut Porntadavity; Chulalongkorn University; Srinakharinwirot University; Mahidol UniversityAim of the study: Curcuma comosa has been known to have potential use in cardiovascular diseases, but its immunoregulatory role in atherosclerosis development and liver toxicity has not been well studied. We therefore investigated the effects of Curcuma comosa on the expression of atherosclerosis-related cytokine genes in rabbits fed a high-cholesterol diet. Materials and methods: Twelve male New Zealand White rabbits were treated with 1.0% cholesterol for one month and were subsequently treated with 0.5% cholesterol either alone, or in combination with 5 mg/kg/day of simvastatin or with 400 mg/kg/day of Curcuma comosa powder for three months. The expression of IL-1, MCP-1, TNF-α, IL-10, and TGF-β in the isolated abdominal aorta and liver were determined by real-time RT-PCR. Liver toxicity was determined by hepatic enzyme activity. Results: Curcuma comosa significantly decreased the expression of pro-inflammatory cytokines, leading to a stronger reduction in IL-1, MCP-1, and TNF-α expression compared to that was suppressed by simvastatin treatment. However, neither Curcuma comosa nor simvastatin affected the expression of anti-inflammation cytokines. In the liver, Curcuma comosa insignificantly decreased the expression of pro-inflammatory cytokines and significantly increased the expression of the anti-inflammatory cytokine IL-10 without altering the activity of hepatic enzymes. In contrast, simvastatin significantly increased the MCP-1 and TNF-α expressions and serum ALT level, without affecting the expression of anti-inflammatory cytokines. Conclusions: In this study, we demonstrated that Curcuma comosa exerts anti-inflammatory activity in the aorta and liver without causing liver toxicity, indicating that Curcuma comosa is a potential candidate as an alternative agent in cardiovascular disease therapy. © 2011 Elsevier Ireland Ltd.
- ItemEffects of vitamin E on the responsiveness of platelets in splenectomized [beta]-thalassemia/hemoglobin E(Mahidol University. Mahidol University Library and Knowledge Center, 2023) Supeenun Unchern; Udom Chantharaksri; Prapon Wilairat; Yupin Sanvarinda; Suthat Fucharoen; Jutamaad SatayavivadThalassemia is a congenital hemolytic anaemia. Beta-thalassemia/ Haemoglobin E (β,-thal/HbE) contritutes to the major portion of thalassemic population living patients in Thailand that possess clinical problems of varying degrees and frequently need of medical attention. Hypoxemia has commonly been found in the splenectomized thalassemic patients (Sp-thal) and are considered a serious clinical syndrome, resulting from pulmonary arterial thrombosis. Hyperfunction of the platelets was suspected as the major cause of this clinical problem and its associated consequences. This study has defined the abnormalities of platelet functions in 6 splenectomized β-thal/Hb E (Sp-, β-thal/HbE ) patients who were splenectonized for more than 5 years. The aggregatability of platelets in the whole blood (WB) and platelet rich plasma (PRP) were performed in a chronolog aggregometer (using impedance and optical aggregometry). One male and 5 female patients, aged 21-38 years old who experienced varying degrees of iron overloading were recruited into this study. They were told not to take aspirin or other nonsteroid anti-inflammatory drugs that were known to affect platelet functions, at least two weeks before the studies. Six normal healthy volunteers in the comparable age groups were served as controls. Blood sample (25 ml) were taken via the scalp vein directly dropped into the clean siliconized glass tube, containing 2.5 ml of 3.2 % sodiµM citrate. Impedance aggregation of the WB were performed within one hour while the optical aggregation of platelets in the PRP were performed within three hours after the blood sampling. The responsiveness of platelets to both mechanical and chemical stimuli were studied using a continuous stirring magnetic bar (speed at 1000 rpm) and the addition of either A D P (0.2-4.0 u M ) or collagen (0.0392.50 ug/ml). Thiobarbituric acid reactive substances (TBARs) appeared in the plasma was detected using fluorometric method and used as a marker for lipid peroxidation. Levels of serµM vitamin E were monitored using HPLC. A complete blood count (CBC) were performrmed by an H1technicon cell analyzer. This study demonstrated that platelets in the WB of all six Sp-,Bthal/HbE were hyperreactive to both mechanical and chemical stimuli. Spontaneous aggregation of the platelets in the WB responding to stirring magnitic bar was found in all cases of the Sp-,β -thal/HbE but not a single case occured in the normal. Platelets of the Sp-β-thal/HbE were more sensitive to ADP and collagen. The minimµM effective concentrations (MEC) of ADP that were needed to aggregate platelets were five-fold less in the Sp-β-thal/HbE (0.2 µM) than that was need in normal volunteers (1.0 µM) and over 30-fold less of collagen (0.08 ug/ml in Sp-β-thal/HbE while more than 1.25 ug/ml in normal) to initiate platelet aggregation in the WB. The same picture applied to platelets in the PRP: the MEC of ADP that induces irreversible platelet aggregation were 0.5, 1.0 µM (Sp-β-thal/ HbE) and 2.0 µM (normal volunteers) and with collagen were 0.16 ug/ml (Sp-,β-thal/HbE ) and 0.625 ug/ml (normal volunteers). Levels of vitamin E in these patients were confirmed low 0.25 mg/dL (Sp-β-thal/HbE) against 0.5 mg/dL (normal volunteers). On the contary, marker of lipid peroxidation was higher in Sp-β-thal/HbE (0.42 nm/ml ) and low (0.14 nm/ml) in normal volunteers. Daily doses of vitamin E (525 IU or 2x525 IU) were given daily to the Sp-β-thal/HbE patients for up to three months. The effect of vitamin E on the reactivity of platelets, TBARs (marker of lipid peroxidation) and levels of vitamin E in the plasma were respectively followed. Vitamin E inhibited platelet responses to ADP and collagen in both the WB and PRP after daily supplementation of vitamin E 525 IU for one month. A significant suppression were also noted with ADP 0.5 µM in the WB (p < 0.05) and ADP 0.5 or 1.0 µM in the PRP model (p < 0.05). Vitamin E also inhibited ATP release in response to 2.0 µM ADP. TBARs, marker of lipid peroxidation in the plasma was significantly lowered, from 0.42 nm/ml (before vitamin E) to 0.17 nm/ml (after two months of vitamin E supplementation). Three months after the cessation of vitamin E supplementation, all these parameters with no exception of any returned to their pretreatment values. These data strongly suggested that the Sp-β-thal/HbE were under severe oxidative stress, as vitamin E (the chain breaking antioxidant) was depleted, resulting in elevation of lipid hydroperoxides in the plasma and thus the hyperactivity of platelets. It is likely that these could be the consequence of iron overloading in thalassemia patients as a good correlation between the levels of serµM ferritin and plasma lipid hydroperoxides was established. Daily supplementation with mega-dose of vitamin E seems to work effectively in inhibiting the oxidative stress in Sp-β-thal/HbE as the hyperreactive platelets were modulated and degrees of lipid peroxidation lowered. Studies of the conventional reactive-oxygen scavenger enzymes, i.e., erythrocyte glutathionne peroxidase ( r-GSH-Px), erythrocyte glutathione reductase (r-GSSG-Rd), erythrocyte catalase (r-CA), and plasma glutathione peroxidase (p-GSH-Px) were also performed in these studies. Significant elevation of r-GSH-Px and r-GSSG-Rd activities were recorded while the activity of p-GSH-Px was suppressed in the Sp-β-thal/HbE patients. No significant difference was noted with the r-CA activity. Supplementation of vitamin E (1050 IU) for six weeks seem to show suppessive effect on the activity of r-GSH-Px. The activities of r-GSSG-Rd, and p-GSH-Px on the other hand were increased after supplementation of vitamin E. It is not known if the effect of vitamin E acts to suppress the oxidative stress or directly interfere with these oxidative scavenging enzymes activities in the assay tubes. It is concluded that platelets of Sp-β-thal/HbE are hyperreactive to both mechanical and chemical stimuli. Iron overloading in the thalassemic blood could be an underling cause of the excessive oxidative stress as demonstrated by a good correlation of serµM ferritin, plasma TBARs, increased activities of the scavenging enzymes and the severely depleted of vitamin E. Supplementation of vitamin E restored the abnormal parameters back towards the direction of healthy volunteers, beside the subjective benefit expressed by the thalassemia subjects. It thus suggested that clinical trials of vitamin E supplementation in the Sp-β-thal/HbE should be considered.
- ItemEvaluation of the protective effects of atropine and diazepam against cypermethrin induced lethality(Mahidol University. Mahidol University Library and Knowledge Center, 2024) Punthip Teeyapant; Jutamaad Satayavivad; Udom Chantharaksri ; Yupin SanvarindaThe protective effects of atropine and diazepam against cypermethrin induced lethality were evaluated in mice. Diazepam was used clinically to control convulsion induced by toxic dose of cypermethrin. It was found that diazepam delayed the onset of death induced by cypermethrin but not AZCORD R. Diazepam 5 mg/kg can reduce the mortality induced by both cypermethrin and AZCORD R only 15-20%, and increasing the dose of diazepam does not produce more reduction in lethality. Atropine can significantly delay the onset of death induced by cypermethrin but not by AZCORD (R) or monocrotophos. Low doses of atropine given 30 minutes before the administration of pesticides are very effective in reducing the percent lethality induced by cypermethrin, AZCORD (R) and monocrotophos. The protective effect of atropine suggested that the toxidc effects of cypermethrin are related to acetylcholine. Overactivity of muscarinic cholinergic function can be the consequence of increased acetylcholine relase and/or inhibition of the cholinesterase activity. In this study, cypermethrin didnot inhibit serum cholinesterase and red blood cell acetylcholinesterase. It is likely that the cholinergic muscarinic overactivity is the result of stimulation of ACh release as reported by the other group of investigators. The results of our study suggested that peripheral muscarinic overstimulation was the major cause of death of cypermethrin-induced lethality in mice. The addition of diazepam did not produce additive protective effect.
- PublicationImprovement of vascular function by chronic administration of a cyclo-oxygenase inhibitor in cholesterol-fed rabbits(2003-05-01) Supath Srisawat; Laddawal Phivthong-Ngam; Supeenun Unchern; Udom Chantharaksri; Piyarat Govitrapong; Yupin Sanvarinda; Mahidol University; Srinakharinwirot University; The Institute of Science and Technology for Research and Development, Mahidol University1. Atherosclerotic cardio- and cerebrovascular disease is a leading cause of mortality in Western countries. Aspirin-like drugs are widely used to prevent and treat these occlusive cardio- and cerebrovascular diseases. The beneficial effects of these drugs have been largely attributed to inhibition of platelet cyclo-oxygenase activity and thromboxane (TX) A2 production. We investigated the effect of an aspirin-like drug, namely indomethacin, on endothelial function, plaque and platelet aggregation and the formation of vasoactive substances during the development of atherosclerosis in cholesterol-fed rabbits. 2. Rabbits were fed 1% cholesterol (n = 8), 1% cholesterol plus 25 mg/day indomethacin (n = 8) or normal rabbit chow (control group; n = 8) for 12 weeks. Urinary excretion rates of 2,3-dinor-TXB2, 6-keto-prostaglandin (PG) F1α, 8-iso-PGF2α, and nitrate were analysed at the beginning of dietary intervention and at 4 weekly intervals thereafter. At the end of the study period, platelet aggregation, aortic plaque formation and endothelium-dependent and -independent vascular functions of isolated aortic rings ex vivo were assessed. 3. Compared with control, in the cholesterol-fed group, urinary 2,3-dinor-TXB2, 6-keto-PGF1α and 8-iso-PGF2α excretion and platelet aggregation were significantly increased (P < 0.05), but urinary excretion of nitrate was decreased (P < 0.05). Treatment with indomethacin significantly reduced platelet aggregation, urinary 2,3-dinor-TXB2, 6-keto-PGF1α, and 8-iso-PGF2α excretion (P < 0.05 vs the cholesterol-fed group) and attenuated the reduction in urinary nitrate excretion. 4. Cholesterol feeding progressively increased aortic intimal thickening and impaired endothelium-dependent vasodilator function (P < 0.05 vs control), whereas indomethacin partially prevented aortic plaque formation and restored endothelium-dependent vasodilation (P < 0.05 vs the cholesterol-fed group). 5. The present study demonstrates that indomethacin reduces the progression of atherosclerotic lesions and improves endothelium-mediated vascular responses ex vivo in cholesterol-fed rabbits. The beneficial effects of indomethacin may be due to its ability to prevent the elevation of platelet aggregation, TXA2 (measured as urinary 2,3-dinor-TXB2 excretion) and 8-iso-PGF2α, formation and to retard the decrease in endogenous nitric oxide synthesis (assessed as urinary excretion of nitrate). Despite indomethacin treatment leading to the suppression of prostacyclin biosynthesis (assessed as urinary 6-keto-PGF1α excretion), according to our data, indomethacin appears to preserve endothelial function.
- PublicationThe in vitro and ex vivo antioxidant properties, hypolipidaemic and antiatherosclerotic activities of water extract of Moringa oleifera Lam. leaves(2008-03-28) Pilaipark Chumark; Panya Khunawat; Yupin Sanvarinda; Srichan Phornchirasilp; Noppawan Phumala Morales; Laddawal Phivthong-ngam; Piyanee Ratanachamnong; Supath Srisawat; K. u S Pongrapeeporn; Mahidol University; Srinakharinwirot University; The Princess of Narathiwat UniversityMoringa oleifera is used in Thai traditional medicine as cardiotonic. Recent studies demonstrated its hypocholesterolaemic effect. However, to be clinically useful, more scientific data are needed. Aim of the Study: We investigated the antioxidant, hypolipidaemic and antiatherosclerotic activities of Moringa oleifera leaf extract. Materials and Methods: Scavenging activity of the extract on 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and the inhibitory effect on Cu2+-induced low-density lipoprotein (LDL) oxidation were determined in in vitro experiment. The effects of the extract on cholesterol levels, conjugated diene (CD) and thiobarbituric acid reactive substances (TBARS) and plaque formations in cholesterol-fed rabbits were investigated. Results: We found that in scavenging DPPH radicals the extract and Trolox®had IC50of 78.15 ± 0.92 and 2.14 ± 0.12 μg/ml, respectively. The extract significantly (P < 0.05) prolonged the lag-time of CD formation and inhibited TBARS formation in both in vitro and ex vivo experiments in a dose-dependent manner. In hypercholesterol-fed rabbits, at 12 weeks of treatment, it significantly (P < 0.05) lowered the cholesterol levels and reduced the atherosclerotic plaque formation to about 50 and 86%, respectively. These effects were at degrees comparable to those of simvastatin. Conclusions: The results indicate that this plant possesses antioxidant, hypolipidaemic and antiatherosclerotic activities and has therapeutic potential for the prevention of cardiovascular diseases. © 2007 Elsevier Ireland Ltd. All rights reserved.
- PublicationIncreased blood oxidative stress in amphetamine users(2010-01-01) Piyarat Govitrapong; Parichart Boontem; Patcharee Kooncumchoo; Sirinthorn Pinweha; Jatuporn Namyen; Yupin Sanvarinda; Smith Vatanatunyakum; Mahidol University; Thanyarak hospitalAmphetamine derivatives have been shown to be a potential brain neurotoxin based on the production of free radicals that occurs after administration. The purpose of this study was to examine the lipid peroxidation and antioxidant enzymes in the blood of amphetamine users. The plasma lipid peroxidation was determined and reported as thiobarbituric acid reactive substance and was significantly increased (+21%), whereas the activities of the erythrocyte antioxidant enzymes glutathione peroxidase, catalase, and superoxide dismutase were significantly decreased (-32%, -14% and -31%, respectively) in amphetamine users. These results implicated the potential role of oxidative stress in amphetamine-induced neurotoxicity. © 2009 Society for the Study of Addiction.
- PublicationInhibitory effect of Curcuma comosa on NO production and cytokine expression in LPS-activated microglia(2006-01-02) Nattinee Jantaratnotai; Pongsak Utaisincharoen; Pawinee Piyachaturawat; Sukumal Chongthammakun; Yupin Sanvarinda; Mahidol UniversityCurcuma comosa is an indigenous plant of Thailand, which has been traditionally and widely used as an anti-inflammatory agent for the treatment of postpartum uterine bleeding and uterine inflammation. However, the scientific investigation on its anti-inflammatory activity has not been reported. In the present study, we investigated the anti-inflammatory effect of the extract from C. comosa on the responses in microglia stimulated with lipopolysaccharide (LPS). Pretreatment of highly aggressively proliferating immortalized (HAPI) cells, a rat microglial cell line, with the hexane extract of C. comosa rhizome at 10- 9to 10- 5g/ml significantly suppressed the levels of NO released from these cells. The attenuation in iNOS protein and mRNA expression was also observed suggesting an interference at transcriptional level. In addition, C. comosa extract inhibited interferon regulatory factor-1 expression which is an essential transcription factor governing the iNOS expression. Moreover, the levels of mRNA expressions of MCP-1 and IL-6 induced by LPS were also prominently decreased in the presence of C. comosa extract. These results suggest that C. comosa extract possesses a strong anti-inflammatory activity and has a potential to be developed as a therapeutic compound for diverse neurological disorders associated with inflammation. © 2005 Elsevier Inc. All rights reserved.
- PublicationModification of platelet shape change parameter by modified phospholipids in oxidized LDL(2009-02-01) Werasak Sutipornpalangkul; Supeenun Unchen; Yupin Sanvarinda; Udom Chantharaksri; Mahidol University; Faculty of Medicine, Siriraj Hospital, Mahidol UniversityBackground: It is believed that the oxidatively modified lipoproteins play a critical role in activating platelets and is a contributing factor in the etiology of a number of cardiovascular-related diseases. Objective: Identify the active component(s) of oxidized LDL that initiated shape change in plasma-free human platelets prepared by a gel filtration method. Material and Method: Shape change parameter of platelets was monitored following exposure platelets to LDL, copper sulfate-oxidized LDL, and different types of lipids extracted of the corresponding LDL. Results: Oxidized LDL, but not native LDL, increased the shape-change parameter in a concentration-dependent manner. Specifically, phosphatidyl serine from oxidized LDL was responsible for this effect. Conclusion: Oxidized phospholipids generated during the oxidative modification of LDL are likely to be the active components responsible for changes in platelet function.
- PublicationModification of platelet shape change parameter by oxidized lipoprotein from β-thalassemia/hemoglobin E(2009-04-01) Werasak Sutipornpalangkul; Supeenun Unchern; Yupin Sanvarinda; Udom Chantharaksri; Suthat Fucharoen; Mahidol University; The Institute of Science and Technology for Research and Development, Mahidol University; Faculty of Medicine, Siriraj Hospital, Mahidol UniversityBackground: β-thalassemia/Hemoglobin E (β-thal/Hb E) is a congenital hemolytic anemia that is prevalent in Thailand. Pulmonary arterial occlusion is the cause of morbidity and mortality in these patients. Abnormality of platelets has been implicated as pathogenesis of this condition. However, the blood-borne factors that induce platelet activation are not identified. Recently, oxidized low-density lipoproteins (ox-LDLs) had been identified in thalassemic blood. Objective: Identify whether oxidized LDL is the blood bone factor that induce platelet activation in β-thal/Hb E patients. Material and Method: Platelet activation was measured by monitoring platelet shape change parameter using plasma-free human platelets. The shape change parameter was monitored following exposure to normal LDL, oxidized LDL, and thalassemic LDL. Results: Oxidized LDL, but not the native LDL and thalassemic LDL, showed platelet activation activity. Oxidation of thalassemic LDL with copper give rise to oxidized LDL with platelet activating activity. However, less copper was needed by LDL from splenectomized β-thal/Hb E patients than those from nonsplencectomized β-thal/Hb E patients. Conclusion: LDL from splenectomized β-thal/Hb E patients is more susceptible for oxidation and gives rise to oxidized-LDL that plays an important role in thrombosis event in these patients.