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Modifications of Cellular Radiation Damage
Published in Kedar N. Prasad, Handbook of RADIOBIOLOGY, 2020
Sodium butyrate is very nontoxic in humans. Doses of 7–10 g/day produced no clinically detectable toxic effect in patients with neuroblastomas.126 Therefore, the author believes that further in vitro and in vivo studies should be performed to evaluate the role of inhibitors of anaerobic glycolysis. Both 5-thio-d-glucose and butyric acid in combination radiation can be considered for a trial in human tumors. It has already been established that these agents are relatively nontoxic in comparison to previously used radiosensitizers. Studies on the modifications of the effect of radiation injuries are important, because they could enhance our knowledge of radiation injuries and could improve the effectiveness of radiation therapy. Therefore, continued efforts in this particular area must be made.
Intracellular Peptide Turnover: Properties and Physiological Significance of the Major Peptide Hydrolases of Brain Cytosol
Published in Gerard O’Cuinn, Metabolism of Brain Peptides, 2020
The effect of thyroid hormone (T3) on the cytosolic TRH degrading enzymes in GH3 cells was also studied. T3 produced a dose-dependent increase in the specific activity of pyroglutamyl peptidase I but not prolyl oligopeptidase after 3 days of exposure (EC50 = 5X10−10M)158. Kinetic studies revealed that the increase was due to a change in Vmax and not Km. The stimulation of PP I by T3 was totally blocked by cycloheximide indicating that the increase was due to enzyme induction. Moreover this effect was cell line specific since T3 did not alter the specific activity of pyroglutamyl peptidase I in the ACTH-secreting cell line At-20. Chronic but not acute administration of T3 also elevated pyroglutamyl peptidase I in selected brain regions of the rat146. These studies provide clear evidence for hormonal regulation of an intracellular peptide degrading enzyme. An effect similar to that produced by T3 was also elicited by sodium butyrate. This short chain fatty acid elevated pyroglutamyl peptidase I 3 fold in GH3 cells159. This increase was additive with that produced by 5-oxoprolinal but not with T3, and could be blocked by cycloheximide. Sodium butyrate also reduced TRH receptor binding suggesting the possibility of a coordinate regulation of TRH receptors and pyroglutamyl peptidase I.
Micronutrients in Improvement of the Standard Therapy in Cancer
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
Anticancer property of butyric acid, a 4-carbon fatty acid, was accidently discovered when sodium butyrate was added as a control for the effect of dibutyryl adenosine 3′-5′-cyclic monophosphate (dibutyryl cAMP) on differentiation of neuroblastoma cells in culture. Dibutyryl cAMP induced irreversible morphological differentiation and growth inhibition; however, sodium butyrate reduced only growth of neuroblastoma cells.145 Sodium butyrate, a potent inhibitor of histone deacetylase119,146 or its analog, phenylbutyrate147,148 induced apoptosis and inhibition of cell proliferation on several rodent and human tumor cell lines in culture. However, clinical studies with these agents produced minimal benefits in cancer patients.149 Therefore, any agents that can enhance the effect of sodium butyrate or phenylbutyrate would enhance the value of these agents in clinical studies. We have reported that alpha-TS at therapeutic doses enhanced the growth-inhibitory effect of sodium butyrate on certain tumor cells in culture (Figure 8.6).150 Retinoic acid increased the effect of phenylbutyrate on human prostate cancer cell growth and angiogenesis in athymic mice.151 Retinoic acid in combination with sodium butyrate also caused a synergistic effects on cell differentiation in poorly differentiated thyroid carcinoma cells in culture; however, in athymic mice carrying the same tumor, the combination of two agents did not reduce the growth of tumor more than that produced by retinoic acid treatment alone152 Antioxidants such as quercetin, curcumin, and ferulic acid enhanced sodium butyrate–induced apoptosis in human erythroleukemic cells in culture.153 Since these studies, 6,276 new studies and reviews on the effect of sodium butyrate on inhibition of cancer growth have been published (PubMed).
The human gut microbiome – a new and exciting avenue in cardiovascular drug discovery
Published in Expert Opinion on Drug Discovery, 2019
Yu Du, Xingxing Li, Chunyan Su, Li Wang, Jiandong Jiang, Bin Hong
Butyrate, one of the SCFAs, is also known as a histone deacetylases inhibitor. Sodium butyrate has been administrated in animals with multiple metabolic benefits, including reduced HFD-induced obesity, greater insulin sensitivity and decreased hepatic steatosis [125]. Tributyrin, a triglyceride containing three butyrate moieties esterified to glycerol, has been designed to overcome the unpleasant taste and odor of butyrate. Tributyrin may be used as a prodrug of butyrate with similar metabolic effects and more favorable pharmacokinetic properties [126]. Tributyrin attenuated the obesity-associated inflammation and insulin-resistance in HFD-fed C57BL/6 male mice. Cresci et al. reported that pretreatment of mice with tributyrin ameliorated acute alcohol-induced liver damage by protecting against the loss of tight junction protein [127]. A recent study confirmed tributyrin administration significantly inhibited the development of atherosclerosis, lipid deposition and macrophage accumulation in the plaque of gnotobiotic ApoE−/- mice, indicating a promising strategy for CVD prevention [40].
LINC00162 participates in the pathogenesis of diabetic nephropathy via modulating the miR-383/HDAC9 signalling pathway
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2020
WenXing Fan, XiaoLing Wen, JinFeng Zheng, KunHua Wang, HongYu Qiu, Jing Zhang, Feng Su
HDAC1 also belongs to HDAC family. In 1996, trapoxin (an HDAC inhibitor) was obtained from nuclear extracts and was used as the affinity tag to identify HDAC1 [20]. Later on, 18 members of the HDAC family were found in the genome of humans. Histone deacetylases are comprised of 18 genes and these genes make up a family and are classified into classes I IV according to the homology of these genes to the corresponding orthologues in yeast. Classes I, II and IV comprise 11 members of the family, which are called classical HDACs, while the seven members of class III are sirtuins. Among them, the classical ones are a new promising class of targets of drugs against cancers. Sodium butyrate is a fatty acid and acts as an HDAC inhibitor in some studies [21–23]. Diabetes seems to significantly influence the function of the kidney according to the evidence that diabetes was associated with enhanced plasma urea and creatinine levels, while significant changes of total protein, plasma albumin and relative kidney weight were not found. NaB used as a post-treatment significantly restored the above mentioned biochemical parameters. Such post-treatment finally significantly ameliorated the histological alterations induced by diabetes, including tubular damage which further includes eosinophilic (pink) staining loss in the cytoplasm of tubules and the detachment of podocytes. The treatment with NaB resulted in the significant restoration of glomerular area (diameter), volume and capsular space increased due to diabetes as well as kidney cytotoxicity. The aforementioned results proved that NaB has renoprotective effects in renal damage induced by diabetes both at structural and functional levels.
Drug repurposing for rheumatoid arthritis: Identification of new drug candidates via bioinformatics and text mining analysis
Published in Autoimmunity, 2022
Ulku Unal, Betul Comertpay, Talip Yasir Demirtas, Esra Gov
A small molecule, ibrutinib, is known to be a potent irreversible inhibitor of Burton tyrosine kinase. It has been identified as a targeted covalent drug and has been reported to provide a significant activity in B-cell malignancies. Ibrutinib is approved for the treatment of various diseases such as mantle cell lymphoma, chronic lymphocytic leukaemia [60], Waldenstrom macroglobulinemia [61], and chronic graft-versus-host disease [62]. According to the PubChem database [63], CHEMBL306380 is an experimental compound that is acutely toxic if ingested. It has been reported that the receptor-binding function targets the tyrosine-protein kinase HCK, which is present in haematopoietic cells and plays an important role in regulating innate immune responses. Sodium butyrate, the other repurposed drug, has been recommended as a candidate for the treatment of RA [64]. According to the DrugBank database [65], TG100801 has been reported as an investigational small molecule and kinase inhibitor for topical use in macular degeneration patients. Sharma et al. demonstrated that when TG100801 was administered topically, inhibited neovascularization and subsequent severity of stromal keratitis in a herpes simplex virus-infected eye [66]. When examining the similarities between RA and macular degeneration, increased rates of angiogenesis can be observed [67]. Although there is no study in the literature investigating the effects of TG100801 on RA, the above similarities may be promising for evaluating TG100801 as a treatment option for RA. It has been reported that JNJ-26483327 may play a role in inhibiting tumour growth, migration, invasion, and metastasis by inhibiting various signalling molecules that play critical roles in tumorigenesis. It has been reported that the synergistic effect of combining herceptin with JNJ-26483327 in tumour inhibition was demonstrated in the BT474 xenograft model of breast cancer [68].