Hydrogen sulfide is one of the most important signal transduction molecules in the body. Its anabolism and catabolism in the gastrointestinal tract(GT) are extremely high, and its role in the physiological and pathological process of the GT is fairly complicated. The study reviewed recent literature on hydrogen sulfide and GT, and proposed that hydrogen sulfide exerted dual modulating effects in the GT; specifically, it promoted the functions of the GT at low concentrations while damaged the GT at high concentrations. Hydrogen sulfide donors or metabolic modifiers exerted their therapeutic effects by restoring the metabolic homeostasis of hydrogen sulfide, and extended their efficacy to other tissues through hydrogen sulfide related gut-axis. Additionally, drugs could deviate hydrogen sulfide metabolism from the normal state due to their instability of structure, local over exposure and/or excessive pharmacological effects, thus inducing toxic and side effects or transforming therapeutic effects into toxic and side effects. This study provided references for the deep research on physiological and pathological mechanisms of hydrogen sulfide and facilitated the development of hydrogen sulfide-related drugs and discovery of their toxicity and efficacy mechanism.
Gastrointestinal Tract ; Hydrogen Sulfide/pharmacology* ; Signal Transduction

Six new ent-abietane diterpenoids, abientaphlogatones A-F (1-6), along with two undescribed ent-abietane diterpenoid glucosides, abientaphlogasides A-B (7-8) and four known analogs were isolated from the aerial parts ofPhlogacanthus curviflorus (P. curviflorus). The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) spectra, and quantum chemical calculations. Notably, compounds 5 and 6 represented the first reported instances of ent-norabietane diterpenoids from the genus Phlogacanthus. In the β-hematin formation inhibition assay, compounds 2, 4, 7-10, and 12 displayed antimalarial activity, with IC₅₀ values of 12.97-65.01 μmol·L^-1. Furthermore, compounds 4, 5, 8, and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H₂O₂ and MPP⁺.
Abietanes/pharmacology* ; Antimalarials ; Hydrogen Peroxide ; Biological Assay ; Plant Components, Aerial

Captopril can have nephrotoxic effects, which are largely attributed to accumulated renin and "escaped" angiotensin II (Ang II). Here we test whether angiotensin converting enzyme-1 (ACE1) inhibition damages kidneys via alteration of renal afferent arteriolar responses to Ang II and inflammatory signaling. C57Bl/6 mice were given vehicle or captopril (60 mg/kg per day) for four weeks. Hypertension was obtained by minipump supplying Ang II (400 ng/kg per min) during the second 2 weeks. We assessed kidney histology by periodic acid-Schiff (PAS) and Masson staining, glomerular filtration rate (GFR) by FITC-labeled inulin clearance, and responses to Ang II assessed in afferent arterioles in vitro. Moreover, arteriolar H₂O₂ and catalase, plasma renin were assayed by commercial kits, and mRNAs of renin receptor, transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) in the renal cortex, mRNAs of angiotensin receptor-1 (AT₁R) and AT₂R in the preglomerular arterioles were detected by RT-qPCR. The results showed that, compared to vehicle, mice given captopril showed lowered blood pressure, reduced GFR, increased plasma renin, renal interstitial fibrosis and tubular epithelial vacuolar degeneration, increased expression of mRNAs of renal TGF-β and COX-2, decreased production of H₂O₂ and increased catalase activity in preglomerular arterioles and enhanced afferent arteriolar Ang II contractions. The latter were blunted by incubation with H₂O₂. The mRNAs of renal microvascular AT₁R and AT₂R remained unaffected by captopril. Ang II-infused mice showed increased blood pressure and reduced afferent arteriolar Ang II responses. Administration of captopril to the Ang II-infused mice normalized blood pressure, but not arteriolar Ang II responses. We conclude that inhibition of ACE1 enhances renal microvascular reactivity to Ang II and may enhance important inflammatory pathways.
Angiotensin II/pharmacology* ; Animals ; Arterioles/metabolism* ; Captopril/pharmacology* ; Hydrogen Peroxide/pharmacology* ; Kidney ; Mice

Pasteurella multocida (P. multocida) infections vary widely, from local infections resulting from animal bites and scratches to general infections. As of yet, no vaccine against P. multocida has been developed, and the most effective way to prevent pathogenic transmission is to clean the host environment using disinfectants. In this study, we identified which disinfectants most effectively inhibited environmental isolates of P. multocida. Three readily available disinfectants were compared: 3% hydrogen peroxide (HP), 70% isopropyl alcohol, and synthetic phenol. In suspension tests and zone inhibition tests, 3% HP was the most promising disinfectant against P. multocida.
Disinfectants/*pharmacology ; Hydrogen Peroxide/*pharmacology ; Microbial Sensitivity Tests ; Pasteurella multocida/*drug effects

The physiological activity of osteoblasts is known to be closely related to increased intracellular Ca2+ activity ([Ca2+]i) in osteoblasts. The cellular regulation of [Ca2+]i in osteoblasts is mediated by Ca2+ movements associated with Ca2+ release from intracellular Ca2+ stores, and transmembrane Ca2+ influx via Na+-Ca2+ exchanger, and Ca2+ ATPase. Reactive oxygen species, such as H2O2, play an important role in the regulation of cellular functions, and act as signaling molecules or toxins in cells. In this study, we investigated the effects of H2O2 on cellular Ca2+ regulation in osteoblasts by measuring intracellular Ca2+ activities using cellular calcium imaging techniques. Osteoblasts were isolated from the femurs and tibias of neonatal rats, and cultured for 7 days. The cultured osteoblasts were loaded with a Ca2+-sensitive fluorescent dye, Fura-2, and fluorescence images were monitored using a cooled CCD camera, and subsequently analyzed using image analyzing software. The results obtained are as follows: (1) The osteoblasts with lower basal Ca2+ activities yielded a transient Ca2+ increase, a Ca2+ spike, while osteoblasts with higher basal Ca2+ activities showed a continuous increase in [Ca2+]i leading to cell death. (2) Ca2+ spikes, generated after removing Na+ from superfusing solutions, were blocked by H2O2 and this was followed by a sustained increase in Ca2+ activity. (3) ATP- induced Ca2+ spikes were inhibited by pretreating with H2O2 and this was followed by a continuous increase of [Ca2+]i. When cells were pretreated with the exogenous nitric oxide (NO) donor S-Nitroso-N-acetylpenicilance (SNAP, 50 microM), treatments of ATP (1 mM) induced a Ca2+ spike-like increase, but [Ca2+]i did not return to the basal level. (4) The expression of inositol- 1,4,5-triphosphate receptor (IP3R) was enhanced by H2O2. Our results suggest that H2O2 modulates intracellular Ca2+ activity in osteoblasts by increasing Ca2+ release from the intracellular Ca2+ stores.
Animal ; Calcium/*metabolism ; Cells, Cultured ; Hydrogen Peroxide/*pharmacology ; Osteoblasts/*drug effects/*metabolism ; Oxidants/*pharmacology ; Rats

BACKGROUNDGlucocorticoid is speculated to be able to have Aspergillus fumigatus (A. fumigatus) being more susceptible to reactive oxygen species (ROS) by inhibiting Afyap1, the transcription factor activating protein-1 (AP-1) homologue in A. fumigatus, which may provide a clue to expand the clinical use of glucocorticoid in patients with fungal infections. In this study, we used dexamethasone to determine the direct effect on oxidative killing susceptibility of A. fumigatus in vitro, as well as the expression level of Afyap1 gene and its target genes (catalase and superoxide dismutase (SOD) genes).

METHODSA. fumigatus spores were treated with different concentrations (0, 0.02, 0.2 mg/ml) of glucocorticoids and assigned to four groups (A: 0.5 hour, B: 2 hours, C: 7 hours, D: 16 hours) according to the time of treatment. The H2O2 oxidative killing assay was done, using the standard method-spot test, in each group of A. fumigatus. We measured the oxidative killing susceptibility as well as the expression level of the gene Afyap1, CATA, SOD1 and SOD2 in A. fumigatus at each group. The antifungal susceptibility to itraconazole and amphotericin B in each group of A. fumigatus was also measured with M38-A2 method.

RESULTSThe oxidative killing susceptibility of A. fumigatus was increased, consistent with the reduction of Afyap1, CATA, SOD1 and SOD2 gene expression level after being treated with dexamethasone for 0.5 hours. However, these observations were disappeared along with being treated for longer time. The antifungal susceptibility to itraconazole and amphotericin B in the A. fumigatus strains treated with dexamethasone indicated no change, compared with those without dexamethasone treatment.

CONCLUSIONDexamethasone can have A. fumigatus being more susceptible to ROS when treated for shorter period (0.5 to 2 hours) via the reduction of Afyap1 gene expression as well as the down-stream enzyme-coding gene expression.

Aspergillus fumigatus ; drug effects ; genetics ; metabolism ; Dexamethasone ; pharmacology ; Fungal Proteins ; genetics ; metabolism ; Hydrogen Peroxide ; pharmacology

Objective: To investigate the effect of permeable resin on the surface structure, microhardness and color of tooth enamel after bleaching. Methods: Premolars extracted for orthodontic needs were selected (provided by the Department of Oral and Maxillofacial surgery of the first affiliated Hospital of Zhengzhou University) and randomly divided into A, B and C 3 groups. Each group was randomly divided into control subgroup, resin subgroup, bleaching subgroup and combined subgroup. Samples in the control subgroup did not receive any treatment. Those in the bleaching subgroup and combined subgroup were treated with cold light whitening. Those in the resin group and combined group were treated with permeable resin. Samples in the group A were observed by scanning electron microscope immediately after treatment and 2 weeks after treatment, and the microhardness of samples in the group B was measured before treatment, immediately after treatment and 2 weeks after treatment (the sample size of each time point was 8 in each subgroup). In group C, chromaticity was measured and chromatic aberration (ΔE value) was calculated before treatment, immediately after treatment and 1 and 2 weeks after treatment (10 samples in each subgroup). Results: Scanning electron microscope showed that the enamel surface of the resin subgroup and the combined group was smooth immediately after treatment, which was basically the same as that of the control subgroup, but covered with resin, and microporous defects and mineral deposits could be seen on the surface of the bleaching subgroup. Two weeks after treatment, the enamel surface of each subgroup was smooth, there was no obvious difference. Immediately after treatment, the microhardness of the control subgroup, resin subgroup, bleaching subgroup and combined subgroup were (354±33), (364±21), (411±30) and (350±17) HV, respectively (F=9.39,P<0.05). The microhardness of the bleaching subgroup was significantly higher than that of the other subgroups (P<0.05). There was no significant difference in microhardness among the four subgroups before treatment and 2 weeks after treatment (F=0.34, 2.75, P>0.05). Immediately after treatment, the ΔE values of the control subgroup, resin subgroup, bleaching subgroup and combined subgroup were 0.00±0.00, 2.29±1.86, 7.20±1.94 and 8.00±0.88, respectively (F=74.21,P<0.05); except that there was no significant difference between bleaching subgroup and combined subgroup (P>0.05), there were significant differences among the other subgroups (P<0.05). There was no significant difference in ΔE value among control subgroup, resin subgroup and bleaching subgroup at each time point (F=1.66, 0.30, 0.96, P>0.05). The difference in the combined subgroup immediately after treatment was significantly higher than that at 1 and 2 weeks after treatment (t=4.73, 4.23,P<0.05), but there was no significant difference between 1 and 2 weeks after treatment (t=0.75, P>0.05), and the color tended to be stable. Conclusions: When whitening healthy enamel, simple cold light whitening or cold light whitening combined with permeation resin can achieve whitening effect.
Color ; Dental Enamel ; Hardness ; Humans ; Hydrogen Peroxide/pharmacology* ; Tooth Bleaching/adverse effects* ; Tooth Bleaching Agents/pharmacology*

OBJECTIVETo compare the antimicrobial efficacy of four endodontic irrigants using an in vitro model infected by Enterococcus faecalis (Ef).

METHODSThe root canals of fifty extracted teeth were infected by Ef in vitro. The test groups were irrigated with 3% H(2)O(2), 2.5% sodium hypochlorite (SH), 2% chloramine-T (CR), and 2% chlorhexidine (CHX), respectively, and the control group was irrigated with 0.9% NaCl. The concentration of Ef in canals of each group was calculated before and after irrigation. The residual bacteria within the dentinal tubules and vitalities of the residual bacteria were also examined.

RESULTSAll chemical irrigants were significantly more effective than 0.9% NaCl (P < 0.05); 2.5% SH and 2% CHX were statistically more effective than 3% H(2)O(2) (P < 0.05). Residual bacteria could be found in the dentinal tubules and propagated 72 h after.

CONCLUSIONS2% CR and 2% CHX had almost the equivalent antimicrobial effect as 2.5% SH, but 3% H(2)O(2) was less effective.

Chloramines ; pharmacology ; Chlorhexidine ; pharmacology ; Dental Pulp Cavity ; microbiology ; Enterococcus faecalis ; drug effects ; Humans ; Hydrogen Peroxide ; pharmacology ; In Vitro Techniques ; Root Canal Irrigants ; pharmacology ; Sodium Hypochlorite ; pharmacology ; Tosyl Compounds ; pharmacology

The cardiac electrophysiological effects of hydrogen sulfide (H(2)S) on pacemaker cells in sinoatrial (SA) nodes of rabbits were examined using intracellular microelectrode technique. The results obtained were as follows: (1) The velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF) in normal pacemaker cells in SA nodes were decreased by NaHS (H(2)S donor) (50, 100, 200 μmol/L) in a concentration-dependent manner; (2) ATP-sensitive K(+) (K(ATP)) channel blocker glybenclamide (Gli, 20 μmol/L) blocked the effect of NaHS (100 μmol/L) on pacemaker cells; (3) Pretreatment with CsCl (2 mmol/L), a blocker of pacemaker current (I(f)), did not affect the effect of NaHS (100 μmol/L) on SA node pacemaker cells; (4) DL-propargylglycine (PPG, 200 μmol/L), an inhibitor of cystathionine γ-lyase (CSE), did not affect the parameters of action potentials in pacemaker cells in SA nodes. All these results suggest that H(2)S exerts a negative chronotropic action on pacemaker cells in SA nodes of rabbits. These effects are likely due to an increase in potassium efflux through opening K(ATP) channels; I(f)is unlikely to play a major role in these effects. In our study, there was no evidence for the generation of endogenous H(2)S by CSE in SA node pacemaker cells.
Action Potentials ; Animals ; Glyburide ; pharmacology ; Hydrogen Sulfide ; pharmacology ; Microelectrodes ; Myocytes, Cardiac ; cytology ; drug effects ; Rabbits ; Sinoatrial Node ; cytology ; Sulfides ; pharmacology

Culture medium and fermentation conditions for lipid production by Rhodosporidium toruloides were optimized with single factor and uniform design experiment. The best medium recipe was found with 70 g/L glucose, 0.1 g/L (NH4)2SO4, 0.75 g/L yeast extract, 1.5 g/L MgSO4. 7H2O, 0.4g/L KH2PO4, sterilized at 121 degrees C for 15 min, and then supplemented with ZnSO4 1.91 x 10(-6) mmol/L, CaCl2 1.50 mmol/L, MnCl2 1.22 x 10(-4) mmol/L and CuSO4 1.00 x 10(-4) mmol/L. The optimal fermentation conditions were as follows: 50 mL of medium (pH 6.0) in 250 mL Erlenmeyer flask with 10% inoculum (28h) under orbital shaking at 200 r/min for 120h at 30 degrees C. Under these conditions, yeast biomass accumulated lipids up to 76.1%.
Basidiomycota ; growth & development ; metabolism ; Copper ; pharmacology ; Culture Media ; Fermentation ; Hydrogen-Ion Concentration ; Lipids ; biosynthesis ; Magnesium Sulfate ; pharmacology ; Zinc ; pharmacology