sodium-bisulfite and Disease-Models--Animal

Ulcerative colitis (UC), an inflammatory disease, is widely thought to be associated with colonic barrier damage and inflammatory response. With the destruction of the colonic barrier, lipopolysaccharide (LPS) enters the liver through the portal vein and causes liver injury. Liver injury in turn exacerbates UC to form a vicious cycle, so the treatment of liver injury cannot be ignored. Andrographolide (Andro) has a protective effect against colitis and liver injury, but with low bioavailability. Andrographolide sodium bisulfite (ASB), a water-soluble sulfonate of Andro, has better bioavailability, whether it has a better curative effect against UC and liver injury is rarely reported. Hence, we investigated the protective effect and potential mechanism of ASB against dextran sulfate sodium (DSS)-induced UC and liver injury in mice. The results showed that treatment with ASB significantly relieved the clinical symptoms of UC and liver injury by reducing disease activity index, inhibiting gut-derived LPS leakage, and improving colonic and hepatic injury, and its curative effect was better than Andro. Moreover, ASB effectively decreased the YAP-mediated colonic inflammation and TLR4/MyD88/NF-κB-mediated pro-inflammatory factor release in the liver. Both colonic and hepatic inflammation were associated with macrophage proinflammatory polarization, but they were significantly inhibited by ASB. ASB showed good safety in the treatment of UC and liver injury and has no nephrotoxicity as previously described. In conclusion, ASB has an effective protective effect on DSS-induced UC and liver injury, mainly by suppressing macrophage proinflammatory polarization from the gut-liver axis.

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Diterpenes; Inflammation; Lipopolysaccharides; Liver; Macrophages; Mice; Mice, Inbred BALB C; NF-kappa B; Sulfites

Various issues related to clinical use of medicines remain unclear, and pharmacists are expected to establish evidence for appropriate use of medicines. The present review summarizes our findings from three areas of research regarding the use of medicines in the operating room: 1) We evaluated the extent of extravasation injury due to thiopental (2.5 mg/100 μL) and propofol (1.0 mg/100 μL) at the macroscopic and histopathologic levels in a rat model. Thiopental, which causes tissue necrosis, can be classified as a "vesicant", and propofol can be classified as an "irritant". Moreover, warming strongly exacerbated the degeneration or necrosis induced by extravasation of thiopental. 2) The cytotoxicity of povidone-iodine solution (PVP-I) for ophthalmic use and that of polyvinyl alcohol-iodine solution (PAI) was compared using a human corneal epithelial cell line. Despite exhibiting equivalent antiseptic effects, the cytotoxicity of PVP-I diluted 16-fold was greater than that of PAI diluted 6-fold. After inactivation of iodine, the cytotoxicity of PVP-I persisted; therefore, to avoid corneal damage, antisepsis should be achieved with PAI. 3) The stability of 1 μg/mL adrenaline when used as an intraocular irrigating solution to maintain pupil dilation was evaluated. After mixing for 6 h, the adrenaline concentration was 65.2% (pH 8.0) of the initial concentration. Moreover, the low concentration of sodium bisulfite in the irrigating solution could have caused adrenaline reduction. Our results strongly suggest that intraocular irrigation solution containing adrenaline should be prepared just prior to use in surgery.

Topics: Animals; Anti-Infective Agents, Local; Cell Line; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Stability; Epinephrine; Evidence-Based Practice; Male; Operating Rooms; Povidone-Iodine; Propofol; Rats; Rats, Wistar; Solutions; Sulfites; Therapeutic Irrigation; Thiopental

The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. The present study was designed to investigate roles of adrenergic signaling and the endogenous hydrogen sulfide producing enzyme cystathionine β-synthetase (CBS) in a previously validated rat model of IBS induced by neonatal colonic inflammation (NCI). Here we showed that NCI-induced visceral hypersensitivity (VH) was significantly attenuated by β2 subunit inhibitor but not by β1 or β3 or α subunit inhibitor. NCI markedly elevated plasma norepinephrine (NE) concentration without alteration in expression of β2 subunit receptors in dorsal root ganglion (DRGs) innervating the colon. In addition, NCI markedly enhanced TRPV1 and CBS expression in the colon DRGs. CBS inhibitor AOAA reversed the upregulation of TRPV1 in NCI rats. In vitro experiments showed that incubation of DRG cells with NE markedly enhanced expression of TRPV1, which was reversed by application of AOAA. Incubation of DRG cells with the H2S donor NaHS greatly enhanced TRPV1 expression. Collectively, these data suggest that activation of adrenergic signaling by NCI sensitizes TRPV1 channel activity, which is likely mediated by upregulation of CBS expression in peripheral sensory neurons, thus contributing to chronic visceral hypersensitivity.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Behavior, Animal; Cystathionine beta-Synthase; Disease Models, Animal; Ganglia, Spinal; Hypersensitivity; Irritable Bowel Syndrome; Male; Norepinephrine; Patch-Clamp Techniques; Propranolol; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-2; Signal Transduction; Sulfites; Tacrolimus; TRPV Cation Channels; Up-Regulation

Patients with long-standing diabetes frequently demonstrate gastric hypersensitivity with an unknown mechanism. The present study was designed to investigate roles for nuclear factor-κB (NF-κB) and the endogenous H2S-producing enzyme cystathionine-β-synthetase (CBS) signaling pathways by examining cbs gene methylation status in adult rats with diabetes. Intraperitoneal injection of streptozotocin (STZ) produced gastric hypersensitivity in female rats in response to gastric balloon distention. Treatment with the CBS inhibitor aminooxyacetic acid significantly attenuated STZ-induced gastric hypersensitivity in a dose-dependent fashion. Aminooxyacetic acid treatment also reversed hyperexcitability of gastric-specific dorsal root ganglion (DRG) neurons labeled by the dye DiI in diabetic rats. Conversely, the H2S donor NaHS enhanced neuronal excitability of gastric DRG neurons. Expression of CBS and p65 were markedly enhanced in gastric DRGs in diabetic rats. Blockade of NF-κB signaling using pyrrolidine dithiocarbamate reversed the upregulation of CBS expression. Interestingly, STZ treatment led to a significant demethylation of CpG islands in the cbs gene promoter region, as determined by methylation-specific PCR and bisulfite sequencing. STZ treatment also remarkably downregulated the expression of DNA methyltransferase 3a and 3b. More importantly, STZ treatment significantly enhanced the ability of cbs to bind DNA at the p65 consensus site, as shown by chromatin immunoprecipitation assays. Our findings suggest that upregulation of cbs expression is attributed to cbs promoter DNA demethylation and p65 activation and that the enhanced interaction of the cbs gene and p65 contributes to gastric hypersensitivity in diabetes. This finding may guide the development and evaluation of new treatment modalities for patients with diabetic gastric hypersensitivity.

Topics: Amino Acids; Analysis of Variance; Animals; Area Under Curve; Case-Control Studies; Chromatin Immunoprecipitation; CpG Islands; Cystathionine beta-Synthase; Diabetes Mellitus, Experimental; Disease Models, Animal; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3A; DNA Methyltransferase 3B; Dose-Response Relationship, Drug; Electromyography; Enzyme Inhibitors; Female; Ganglia, Spinal; Hypersensitivity; Membrane Potentials; Methylation; Neoplasm Proteins; NF-kappa B; Nucleocytoplasmic Transport Proteins; Oxamic Acid; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells; Stomach Diseases; Sulfites; Up-Regulation