(S)-Methylisothiourea (S-Methylisothiourea) Sulfate (SMT) is a potent, selective and competitive inhibitor of inducible nitric oxide synthase (iNOS). S-Methylisothiourea sulfate prevents the NO-mediated cytotoxic effect of LPS in cultured macrophages. S-Methylisothiourea sulfate (100 nM-100 μM) exhibits inhibitory effects on LPS (ug/mL)-induced nitrite production in J774.2 macrophages and rat aortic vascular smooth muscle cells. SMT is equipotent with MeArg in inhibiting the endothelial, constitutive isoform of NOS in vitro and causes increases in blood pressure similar to those produced by MeArg in normal rats. SMT, however, dose-dependently reverses (0.01-3 mg/kg) the hypotension and the vascular hyporeactivity to vasoconstrictor agents caused by endotoxin [bacterial lipopolysaccharide (LPS), 10 mg/kg, i.v.] in anesthetized rats. Moreover, therapeutic administration of SMT (5 mg/kg, i.p., given 2 hr after LPS, 10 mg/kg, i.p.) attenuates the rises in plasma alanine and aspartate aminotransferases, bilirubin, and creatinine and also prevents hypocalcaemia when measured 6 hr after administration of LPS. SMT (1 mg/kg, i.p.) improves 24-hr survival of mice treated with a high dose of LPS (60 mg/kg, i.p.)[1]. In addition, S-methylisothiourea (SMT) had anti-inflammatory effects in treating herpes simplex encephalitis in mice, and SMT also induced apoptosis of herpes simplex virus (HSV-1)-infected microglial cells[2]. SMT (30 mg/kg) attenuates the MIA-induced pain and histopathological changes in the knee joint. The antinociceptive and antiarthritic effects of SMT were mediated by inhibiting cartilage damage and suppression of NO in synovial fluid[3]. HOT (Hyperbaric oxygen treatment) and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately[4].
S-Methylisothiourea sulfate/S-甲基异硫脲半硫酸盐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
J774.2 macrophages
6 µM
24 hours
To evaluate the inhibitory effect of SMT on LPS-induced NO production. Results showed SMT is a potent inhibitor of iNOS with an EC50 of 6 μM.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12472-6.
HL-1 cells
10 µM
24 hours
To investigate the inhibitory effect of SMT on iNOS protein expression in PA-induced HL-1 cells
Int J Mol Sci. 2023 Jan 3;24(1):858.
Rat aortic smooth muscle cells
2 µM
48 hours
To evaluate the inhibitory effect of SMT on LPS and IFN-γ-induced NO production. Results showed SMT is a potent inhibitor of iNOS with an EC50 of 2 μM.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12472-6.
FHM cells
0, 1 µM, 10 µM, 0.1 mM, 1 mM
48 hours
To investigate the inhibitory effect of SMT on GCRV-induced apoptosis. Results showed that as SMT concentration increased, cytopathic effects were attenuated and apoptosis rate decreased.
Int J Mol Sci. 2019 Dec 16;20(24):6335.
S-Methylisothiourea sulfate/S-甲基异硫脲半硫酸盐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Wistar rats
Endotoxic shock model
Intravenous injection
0.01-3 mg/kg
Single dose
To evaluate the effect of SMT on blood pressure in endotoxic shock rats. Results showed SMT dose-dependently reversed LPS-induced hypotension and vascular hyporeactivity.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12472-6.
Sprague-Dawley rats
Pulmonary granulomatous inflammation model
Intraperitoneal injection
10 mg
Once daily for 3 consecutive days
Inhibited NO production, significantly reduced monocyte/macrophage infiltration and inhibited induction of monocyte chemoattractant protein-1
Am J Pathol. 1996 Dec;149(6):2005-22
Rare minnow
GCRV infection model
Intraperitoneal injection
100 mg/kg
Single dose, observed until hemorrhage developed
To investigate the inhibitory effect of SMT on GCRV-induced hemorrhage. Results showed that SMT significantly reduced NO content, caspase activities, and hemorrhage symptoms.
Int J Mol Sci. 2019 Dec 16;20(24):6335.
Sprague-Dawley rats
Hemorrhagic shock model
Perfusate
100 μM
Single dose, measurements taken 10 min post-administration
To investigate the effect of S-methylisothiourea sulfate on hepatic microcirculatory function after hemorrhagic shock, showing no significant effect on sinusoidal flow, hepatic redox state, or function
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