The aim of our study was to evaluate the safety and effectiveness of the free combination of amlodipine/valsartan in patients with arterial hypertension in a real-life setting.
Matched MeSH terms: Dose-Response Relationship, Drug
BACKGROUND: Sunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D). Paracetamol was administered 15 min before sunitinib. Mice were sacrificed 4 h post sunitinib administration.
RESULTS: Group-A serum ALT and AST levels were 14.29 ± 2.31 U/L and 160.37 ± 24.74 U/L respectively and increased to 249.6 ± 222.7 U/L and 377.1 ± 173.6 U/L respectively in group-B; group-C ALT and AST ranged 36.75-75.02 U/L and 204.4-290.3 U/L respectively. After paracetamol coadministration with low sunitinib doses (group-D), ALT and AST concentrations ranged 182.79-221.03 U/L and 259.7-264.4 U/L respectively, lower than group-B. Paracetamol coadministration with high sunitinib doses showed higher ALT and AST values (range 269.6-349.2 U/L and 430.2-540.3 U/L respectively), p < 0.05. Hepatic histopathology showed vascular congestion in group-B; mild congestion in group-C (but lesser than in group-B and D). In group-D, at low doses of sunitinib, lesser damage than in group-B occurred but larger changes including congestion were observed at high sunitinib doses. BUN levels were higher (p < 0.05) for group-B (33.81 ± 5.68 mg/dL) and group-D (range 35.01 ± 6.95 U/L to 52.85 ± 12.53 U/L) compared to group-A (15.60 ± 2.17 mg/dL) and group-C (range 17.50 ± 1.25 U/L to 26.68 ± 6.05 U/L). Creatinine remained unchanged. Renal congestion and necrosis was lower in group-C than group-B but was higher in group-D (p > 0.05). Mild cardiotoxicity occurred in groups B, C and D. Brain vascular congestion occurred at high doses of sunitinib administered alone or with paracetamol. Hepatic and renal biomarkers correlated with histopathology signs.
CONCLUSIONS: Paracetamol and sunitinib coadministration may lead to dose dependent outcomes exhibiting mild hepatoprotective effect or increased hepatotoxicity. Sunitinib at high doses show renal, cardiac and brain toxicity. Liver and renal function monitoring is recommended.
Matched MeSH terms: Dose-Response Relationship, Drug
Coriandrum sativum L., commonly known as coriander and belonging to the family Apiaceae (Umbelliferae), is cultivated throughout the world for its nutritional value. The present study was undertaken to investigate the effects of fresh Coriandrum sativum leaves (CSL) on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. In this study, CSL (5, 10 and 15% w/w of diet) was fed orally with a specially prepared diet for 45 days consecutively to experimental animals. Elevated plus-maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam, scopolamine and ageing-induced amnesia served as the interoceptive behavioral models.
Matched MeSH terms: Dose-Response Relationship, Drug
The possible mechanisms of action in the antinociceptive activity induced by systemic administration (intraperitoneal, i.p.) of flavokawin B (FKB) were analysed using chemical models of nociception in mice. It was demonstrated that i.p. administration of FKB to the mice at 0.3, 1.0, 3.0 and 10 mg/kg produced significant dose-related reduction in the number of abdominal constrictions. The antinociception induced by FKB in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with L-arginine, the substrate for nitric oxide synthase or glibenclamide, the ATP-sensitive K(+) channel inhibitor, but was enhanced by methylene blue, the non-specific guanylyl cyclase inhibitor. FKB also produced dose-dependent inhibition of licking response caused by intraplantar injection of phorbol 12-myristate 13-acetate, a protein kinase C activator (PKC). Together, these data indicate that the NO/cyclic guanosine monophosphate/PKC/ATP-sensitive K(+) channel pathway possibly participated in the antinociceptive action induced by FKB.
Matched MeSH terms: Dose-Response Relationship, Drug
Morinda elliptica Ridley (Rubiaceae) has been used traditionally as a medicine to treat various diseases in Malaysia and southeast Asia. In the present study we investigated the immunomodulatory effects of damnacanthal isolated from the roots of Morinda elliptica. The immunomodulatory effect of this compound was evaluated by using the lymphocyte proliferation assay with mouse thymocytes and human peripheral blood mononuclear cells (PBMC). In addition, the effect of the compound on PBMC cell cycle progression was studied by using flow cytometry. The production of human interleukin-2 and human inteleukin-12 cytokines was also assessed using the enzyme linked immunosorbent assay (ELISA) technique. The lymphocyte proliferation assay showed that damnacanthal was able to activate mouse thymocytes and PBMC at a low concentration (0.468 microg/mL). Moreover, the production of human interleukin-2 and human interleukin-12 cytokines in the culture supernatant from damnacanthal activated lymphocytes was markedly up-regulated at 24 h and sustained until 72 h with a slight decrease with time. A positive correlation was found between the level of these two cytokines and the MTT-based proliferation assay. Based on the above results, damnacanthal can act as an immunomodulatory agent which may be very useful for maintaining a healthy immune system.
Matched MeSH terms: Dose-Response Relationship, Drug
Goniothalamin (GN), a styryl-lactone isolated from Goniothalamus andersonii, has been demonstrated to possess antirestenostic properties by inducing apoptosis on coronary artery smooth muscle cells (CASMCs). In this study, the molecular mechanisms of GN-induced CASMCs apoptosis were further elucidated. Apoptosis assessment based on the externalization of phosphatidylserine demonstrated that GN induces CASMCs apoptosis in a concentration-dependent manner. The GN-induced DNA damage occurred with concomitant elevation of p53 as early as 2 h, demonstrating an upstream signal for apoptosis. However, the p53 elevation in GN-treated CASMCs was independent of NAD(P)H: quinone oxidoreductase 1 and Mdm-2 expression. An increase in hydrogen peroxide and reduction in free thiols confirmed the role for oxidative stress in GN treatment. Pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-FMK) that significantly abrogated GN-induced CASMCs apoptosis suggested the involvement of caspase(s). The role of apical caspase-2, -8, and -9 was then investigated, and sequential activation of caspase-2 and -9 but not caspase-8 leading to downstream caspase-3 cleavage was observed in GN-treated CASMCs. Reduction of ATP level and decrease in oxygen consumption further confirmed the role of mitochondria in GN-induced apoptosis in CASMCs. The mitochondrial release of cytochrome c was seen without mitochondrial membrane potential loss and was independent of cardiolipin. These data provide insight into the mechanisms of GN-induced apoptosis, which may have important implications in the development of drug-eluting stents.
Matched MeSH terms: Dose-Response Relationship, Drug
This study set out to investigate the impact of chronic cumulative blockade of angiotensin II and adrenoceptors in WKY and SHR and to explore how the renovascular responses to adrenergic and angiotensin II receptor agonists may be interdependent. Rats were treated with either losartan, carvedilol or losartan+carvedilol for 7 days and on day eight, animals were pentobarbitone anaesthetized and prepared for renal haemodynamic study. Dose-response relationships were determined in terms of reduction/elevation in the magnitude of renal blood flow in response to intrarenal arterial injection of dopamine, phenylephrine and isoprenaline. Renal vascular responses were blunted in WKY and SHR treated with either losartan or carvedilol as compared to their untreated counterparts (P<0.05). In the combined treated rats, the vascular responses to isoprenaline and phenylephrine were restored to levels observed in the untreated rats, but the renal vasoconstrictor responses to dopamine decreased (P<0.05) in both WKY and SHR. There was a reduction of (P<0.05) in the magnitude of the isoprenaline induced renal vasodilation in all SHR as compared to WKY groups. The data obtained showed that the renal vascular action of dopamine, phenylephrine and isoprenaline depended on an intact renin-angiotensin system (RAS) in WKY and SHR. Treatment with losartan or carvedilol blunted the renal vasoconstrictor/vasodilator responses to sympathomimetics which was attenuated with the combined treatment. These observations using chronic blockade of adrenergic and angiotensin receptors demonstrated that there was a long standing interdependency between the RAS and sympathetic nervous system (SNS) in determining the responsiveness of the renal vasculature of normal and hypertensive rats.
Matched MeSH terms: Dose-Response Relationship, Drug
Curcumin is a highly pleiotropic molecule with significant regulatory effects upon inflammation and inflammatory related diseases. However curcumin has one major important limitation in which it has poor bioavailability. Design of synthetic structural derivatives of curcumin is but one approach that has been used to overcome its poor bioavailability while retaining, or further enhancing, its drug-like effects. We have synthesized a series of curcumin analogues and describe the effects of 2,6-bis-4-(hydroxyl-3-methoxy-benzylidine)-cyclohexanone or BHMC upon nitric oxide and cytokine synthesis in cellular models of inflammation. BHMC showed a significant dose-response inhibitory action upon the synthesis of NO and we have shown that this effect was due to suppression of both iNOS gene and enzyme expression without any effects upon scavenging of nitrite. We also demonstrated that BHMC has a very minimal effect upon iNOS activity with no effect at all upon the secretion of PGE(2) but has a strong inhibitory effect upon MCP-1 and IL-10 secretion and gene expression. Secretion and gene expression of TNF-alpha and IL-6 were moderately inhibited whereas IL-8 and IL-1beta were not altered. We conclude that BHMC selectively inhibits the synthesis of several inflammatory mediators. BHMC should be considered a promising drug lead for preclinical and further pharmacological studies.
Matched MeSH terms: Dose-Response Relationship, Drug
Appropriate drug selection and dosing for patients with chronic kidney disease (CKD) is important to avoid unwanted drug effects and ensure optimal patient outcomes.
Matched MeSH terms: Dose-Response Relationship, Drug
The ethanolic extract of Alpinia conchigera Griff. leaves (EACL) was evaluated for its antinociceptive and anti-inflammatory activities in several in vivo experimental models. Antinociceptive activity was determined using the acetic acid-induced abdominal writhing test, the hot plate test and the formalin test. Anti-inflammatory activity was determined using the carrageenan-induced paw edema test. The extract (30, 100 and 300 mg/kg i.p.) was found to possess significant, dose-dependent inhibitory activity in all test models. In addition, the antinociceptive effect of the extract in the acetic acid-induced writhing and hot plate tests was reversed by naloxone, suggesting that this activity is mediated through activation of the opioid system. These findings suggest that EACL presents notable analgesic and anti-inflammatory activities, which support its folkloric use for painful and inflammatory conditions.
Matched MeSH terms: Dose-Response Relationship, Drug
The protective effect of methanol extracts of Cassia fistula (flowers, leaves and bark) was examined in vitro in human umbilical vein endothelial cells (HUVEC) against toxicity induced by glycated protein (GFBS) in vitro. The experiments consisted of eight groups of HUVEC with five flasks in each group. Group I was treated with 15% FBS, group II with GFBS (70 microM) alone, and the other six groups were treated with GFBS plus 25 and 50 microg of each of the three types of C. fistula extracts. After 72 h of incubation, cells were collected and tested for lipid peroxidation, antioxidant enzyme activities and glutathione S-transferase (GST). The protective effect of C. fistula extracts against GFBS-induced cytotoxicity was examined in HUVEC by using trypan blue exclusion and MTT assays. Results showed that HUVEC incubated with GFBS alone showed a significant (P < 0.001) elevation of lipid peroxidation accompanied by depletion of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), in addition to decreased cytosolic GST. Treatment of HUVEC with C. fistula extracts at a concentration of 25 and 50 microg significantly decreased lipid peroxidation and normalized the activities of the antioxidant enzymes and GST levels in a concentration-dependent manner. Morphological changes of HUVEC were compared with respective controls; in addition, the C. fistula extracts increased the viability of HUVEC damaged by GFBS. A protective effect of C. fistula extracts on HUVEC against GFBS-induced toxicity suggested a potential beneficial effect of the extract in preventing diabetic angiopathies.
Matched MeSH terms: Dose-Response Relationship, Drug
This study was performed to determine the antinociceptive and anti-inflammatory activities of aqueous extract of Kaempferia galanga leaves using various animal models. The extract, in the doses of 30, 100, and 300 mg/kg, was prepared by soaking (1:10; w/v) the air-dried powdered leaves (40 g) in distilled water (dH(2)O) for 72 h and administered subcutaneously in mice/rats 30 min prior to the tests. The extract exhibited significant (P < 0.05) antinociceptive activity when assessed using the abdominal constriction, hot-plate and formalin tests, with activity observed in all tests occurring in a dose-dependent manner. Furthermore, the antinociceptive activity of K. galanga extract was significantly (P < 0.05) reversed when prechallenged with 10 mg/kg naloxone. The extract also produced a significantly (P < 0.05) dose-dependent anti-inflammatory activity when assessed using the carrageenan-induced paw-edema test. In conclusion, this study demonstrated that K. galanga leaves possessed antinociceptive and anti-inflammatory activities and thus supports the Malay's traditional uses of the plant for treatments of mouth ulcer, headache, sore throat, etc.
Matched MeSH terms: Dose-Response Relationship, Drug
This study was performed out to establish the antinociceptive, anti-inflammatory, and antipyretic properties of an aqueous extract of Dicranopteris linearis leaves in experimental animals. The antinociceptive activity was measured using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory and antipyretic activities were measured using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. The extract, obtained after 72 h soaking of the air-dried leaves in distilled water and then prepared in the doses of 13.2, 66.0, 132.0, and 660.0 mg/kg, was administered subcutaneously 30 min before subjecting the animals to the assays mentioned above. Generally, the extract, at all doses used, was found to have significant (P < 0.05) concentration-independent antinociceptive, anti-inflammatory, and anti-pyretic activity. In conclusion, the aqueous extract of D. linearis has antinociceptive, anti-inflammatory, and antipyretic activity, supporting previous claims of its traditional use by the Malays to treat various ailments, particularly fever.
Matched MeSH terms: Dose-Response Relationship, Drug
1 The present study investigated the effect of streptozotocin-induced diabetes on alpha(1)-adrenoceptor subtypes in rat renal resistance vessels. 2 Studies on renal haemodynamics were carried out 7 days after the last streptozotocin. Changes in renal blood flow were recorded in response to electrical stimulation of the renal nerve (RNS) and a range of adrenergic agonists; noradrenaline (NA), phenylephrine (PE) and methoxamine (MTX), either in the absence or the presence of nitrendipine (Nit), 5-methylurapidil (MEU), chlorethylclonidine (CEC) or BMY 7378. 3 In non-diabetic animals, Nit, MEU and BMY 7378 significantly attenuated renal vasoconstriction induced by adrenergic agonists, while CEC showed a significant accentuation in RNS-induced responses without having a significant effect on responses to adrenergic agonists. In diabetic rats, renal vasoconstriction was also significantly reduced in Nit-, MEU- and BMY 7378-treated groups and CEC potentiated RNS-induced contractions caused a change similar to that observed in non-diabetic rats. BMY 7378 significantly (P < 0.05) attenuated the PE- and MTX-induced vasoconstrictions but did not cause any significant (P > 0.05) alteration in the RNS- and NA-induced responses. 4 The results showed functional co-existence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of SD rats irrespective of the presence of diabetes. A possible minor contribution of prejunctional alpha-adrenoceptor subtype has also been suggested in either experimental group, particularly possible functional involvement of alpha(1B)-adrenoceptor subtypes in non-diabetic SD rats.
Matched MeSH terms: Dose-Response Relationship, Drug
Xanthorrhizol is a natural sesquiterpenoid compound isolated from the rhizome of Curcuma xanthorrhizza Roxb (Zingerberaceae). Recent studies of xanthorrhizol in cell cultures strongly support the role of xanthorrhizol as an antiproliferative agent. In our study, we tested the antiproliferative effect of xanthorrhizol using different breast cancer cell lines. The invasive breast cancer cell line, MDA-MB-231, was then selected for further investigations. Treatment with xanthorrhizol caused 50% growth inhibition on MDA-MB-231 cells at 8.67 +/- 0.79 microg/ml as determined by sulforhodamine B (SRB) assay. Hoechst 33258 nuclear staining assay showed the rate of apoptosis of MDA-MB-231 cells to increase in response to xanthorrhizol treatment. Immunofluorescence staining using antibody MitoCapture and fluorescein isothiocyanate (FITC)-labeled cytochrome c revealed the possibility of altered mitochondrial transmembrane potential and the release of cytochrome c respectively. This was further confirmed by Western-blotting, where cytochrome c was showed to migrate from mitochondrial fraction to the cytosol fraction of treated MDA-MB-231 cells. Caspase activity assay showed the involvement of caspase-3 and caspase-9, but not caspase-6 or caspase-8 in MDA-MB-231 apoptotic cell death. Subsequently, cleavage of PARP-1 protein is suggested. These data suggest treatment with xanthorrhizol modulates MDA-MB-231 cell apoptosis through the mitochondria-mediated pathway subsequent to the disruption of mitochondrial transmembrane potential, release of cytochrome c, activation of caspase-3 and caspase-9, and the modulation of PARP-1 protein.
Matched MeSH terms: Dose-Response Relationship, Drug
The aims of this study are to determine the mutagenicity of a locally produced polyhydroxybutyrate (PHB) using Salmonella mutagenicity test and to find out if PHB altered the expression of p53 and c-myc proto-oncogenes and bcl-xl and bcl-xs anti-apoptotic genes in the human fibroblast cell line, MRC-5. Different concentrations of PHB were incubated with special genotypic variants of Salmonella strains (TA1535, TA1537, TA1538, TA98 and TA100) carrying mutations in several genes both with and without metabolic activation (S9) and the test was assessed based on the number of revertant colonies. The average number of revertant colonies per plate treated with PHB was less than double as compared to that of negative control. For the gene expression analyses, fibroblast cell lines were treated with PHB at different concentrations and incubated for 1, 12, 24 and 48 h separately. The total RNA was isolated and analysed for the expression of p53, c-myc, bcl-xl and bcl-xs genes. The PHB did not show over or under expression of the genes studied. The above tests indicate that the locally produced PHB is non-genotoxic and does not alter the expression of the proto-oncogenes and anti-apoptotic genes considered in this study.
Matched MeSH terms: Dose-Response Relationship, Drug
Angiotensin 1-7, a heptapeptide derived from metabolism of either angiotensin I or angiotensin II, is a biologically active peptide of the renin-angiotensin system. The present study investigated the effect of angiotensin 1-7 on the vasopressor action of angiotensin II in the renal and mesenteric vasculature of Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and streptozotocin-induced diabetic rats. Angiotensin II-induced dose-dependent vasoconstrictions in the renal vasculature. The pressor response was enhanced in the SHR and reduced in the streptozotocin-diabetic rat compared to WKY rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in the renal vasculature of WKY and SHR rats. However, the ability to reduce angiotensin II response was diminished in diabetic-induced rat kidneys. The effect of angiotensin 1-7 was not inhibited by 1-[(4-(Dimethylamino)-3-methylphenyl] methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate (PD123319), an angiotensin AT(2) receptor antagonist. (D-ALA(7))-Angiotensin I/II (1-7) (D-ALA) (an angiotensin 1-7 receptor antagonist), indomethacin (a cyclo-oxygenase inhibitor), and N(omega)-Nitro-L-Arginine Methyl Ester (L-NAME)(a nitric oxide synthetase inhibitor) abolished the attenuation by angiotensin 1-7 in both WKY rats and SHR, indicating that its action is mediated by angiotensin 1-7 receptor that is either coupled to the release of prostaglandins and/or nitric oxide. The vasopressor responses to angiotensin II in mesenteric vasculature bed was also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses to angiotensin II were relatively smaller in SHR but no significant difference was observed between WKY and streptozotocin-induced diabetic rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in WKY, SHR and diabetic-induced mesenteric bed. The attenuation was observed at the lower concentrations of angiotensin II in WKY and diabetic-induced rats but at higher concentrations in SHR. Similar observation as in the renal vasculature was seen with PD123319, D-ALA, and L-NAME. Indomethacin reversed the attenuation by angiotensin 1-7 only in the SHR mesenteric vascular bed. The present findings support the regulatory role of angiotensin 1-7 in the renal and mesenteric vasculature, which is differentially altered in hypertension and diabetes.
Matched MeSH terms: Dose-Response Relationship, Drug
This study investigated whether the alpha(1)-adrenoceptor subtype(s) mediating the vasoconstrictor actions of the renal sympathetic nerves were altered in rats with cisplatin-induced renal failure. Male Wistar Kyoto rats were used and half received cisplatin (5 mg/kg i.p.) to induce renal failure and were taken for study 7 days later. The renal blood flow reductions caused by electrical renal nerve stimulation and close intra-renal administration of noradrenaline, phenylephrine and methoxamine were determined before and after amlodopine (AMP), 5-methylurapidil (MeU), chloroethylclonidine (CEC) or BMY 7378. Water intake and creatinine clearance were decreased (P<0.05) by 40-50% while fractional excretion of sodium was increased two-fold in the cisplatin treated rats. Mean arterial pressure was higher, 110+/-2 versus 102+/-3 mmHg and renal blood flow was lower, 10.7+/-0.9 versus 18.9+/-0.1 ml/min/kg in the renal failure rats (both P<0.05). AMP, MeU and BMY 7378 decreased (all P<0.05) the adrenergically induced renal vasoconstrictor responses in the renal failure groups by 30 to 50% and in normal rats by 20 to 40%. In the presence of CEC, renal nerve stimulation and noradrenaline and methoxamine induced renal vasoconstrictor responses were enhanced (all P<0.05) in the renal failure but not in the normal rats. These data showed that alpha(1A)- and alpha(1D)-adrenoceptors were the major subtypes in mediating adrenergically induced renal vasoconstriction but there was no substantial shift in subtype in renal failure. The contribution of alpha(1B)-adrenoceptor subtypes either pre- or post-synaptic appeared to be raised in the renal failure rats.
Matched MeSH terms: Dose-Response Relationship, Drug
The present study was carried out to investigate on the possible involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate (L-arginine/NO/cGMP) pathway in the aqueous extract of Muntingia calabura (AEMC) leaves antinociception in mice assessed by abdominal constriction test. The AEMC, obtained by soaking the dried leaves in distilled water (DH(2)O) (1 : 2; w/v) for 24 h, was prepared in concentrations of 10%, 50% and 100% that were approximately equivalent to doses of 27, 135 and 270 mg/kg, and administered subcutaneously (s.c.) 5 min after pre-treatment (s.c.) of mice with DH(2)O, L-arginine (20 mg/kg), N(G)-monomethyl-L-arginine acetate (L-NMMA; 20 mg/kg), N(G)-nitro-L-arginine methyl esters (L-NAME; 20 mg/kg), methylene blue (MB) (20 mg/kg), respectively. The AEMC was found to exhibit a concentration-dependent antinociception after pre-challenge with DH(2)O. Interestingly, pre-treatment with L-arginine was found to block significantly (P < 0.05) the AEMC antinociception but only at the highest concentration (100%) of AEMC used. On the other hand, pre-treatment with L-NAME was found to significantly (P < 0.05) enhance the low concentration but inhibit the high concentration AEMC antinociception. MB was found to significantly (P < 0.05) enhance AEMC antinociception at all concentrations used. Except for the higher concentration of AEMC used, co-treatment with L-NAME was found to insignificantly and significantly (P < 0.05) reverse the L-arginine effect when given alone or with low concentration AEMC, respectively. In addition, co-treatment with MB significantly (P < 0.05) reversed the L-arginine effect when given alone or with 10% concentration AEMC but failed to affect the activity of the rest of concentrations used. As a conclusion, this study has demonstrated the involvement of L-arginine/NO/cGMP pathway in AEMC antinociception.
Matched MeSH terms: Dose-Response Relationship, Drug