ascorbic-acid and Cystitis

Our present study aimed to unravel the therapeutic biotargets of vitamin C (VC) against cystitis glandularis (CG), and to elucidate the molecular mechanisms for VC treating CG.. Network pharmacology was used to predict therapeutic targets of VC against CG, and to identify molecular mechanisms. In addition, further human and animal studies were designed to validate the bioinformatic findings through biochemical tests, computerized tomography scans, and immunostaining assays.. In bioinformatic analyses, pathogenic targets of CG and putative targets of VC were identified, respectively. An interaction network between biological target and functional protein was produced before screening and collecting the key therapeutic targets of VC against CG, biological processes, and signaling pathways. In addition, ingenuity pathway analysis with cloud platform indicated that anti-CG mechanisms of VC were achieved through modulating a cluster of molecular pathways, such as tumor necrosis factor (TNF) pathway. Meanwhile, 18 core targets of VC against CG were identified, and the most important TNF, interleukin-6 (IL6), and Jun biotargets were obtained, respectively. In further validation in human study, cellular TNF-α, IL6, and c-Jun expressions in patient's CG samples were elevated significantly, accompanied with detectable urinary tract infection. Beneficially, VC-dosed CG mice resulted in downregulated expressions of endogenous TNF-α, IL6, and c-Jun in blood and bladder samples.. Collectively, these bioinformatic findings and experimentative data uncover the therapeutic targets and biological mechanisms of VC for treating CG, in which the key biomarkers of TNF-α, IL6, and c-Jun may be the potential molecules for treating CG in clinical application.

Topics: Animals; Ascorbic Acid; Biomarkers; Cystitis; Female; Gene Expression Regulation; Humans; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Male; Mice; Middle Aged; Protein Interaction Maps; Signal Transduction; Transcription Factor RelA; Tumor Necrosis Factor-alpha

The protective roles of lipoic acid (LA)/vitamin C (VC) and mesna on preventing cyclophosphamide (CYP)-induced haemorrhagic cystitis (HC) were investigated. Swiss mice were divided into five groups randomly. HC was induced by a single dose of CYP injection (150-mg kg(-1) bodyweight). Group I was injected with saline (four times in total) throughout as control group. Group II received CYP and three equal doses of saline. Group III received CYP and three doses of mesna, whereas Group IV (or Group V) received CYP, mesna + two doses of VC (or LA). All injections were performed intraperitoneally. After 24 h of cystitis induction, the bladders were collected for all the experiments. Histological characterization showed that CYP injection resulted in severe HC. Reactive oxygen species (ROS) and thiobarbituric acid reactive substances' levels were increased in CYP group. The activities of antioxidant enzymes, e.g. superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase, were inhibited significantly in CYP groups, respectively. In addition, activation of c-jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in the mechanism of CYP-induced HC but not extracellular signal regulated kinases (ERK). Significant suppression of p38 phosphorylation on Group V suggests that LA and mesna may have synergistic beneficial effect. In Groups III-V, all the parameters of HC and oxidative stress were inhibited significantly. Taking together, we found that these results illustrated that ROS play an important role on CYP-induced HC and the administration of LA/VC with mesna may have therapeutic potential against CYP-induced bladder HC.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cyclophosphamide; Cystitis; Drug Synergism; Hematuria; MAP Kinase Signaling System; Mesna; Mice; Organ Size; Phosphorylation; Protective Agents; Random Allocation; Reactive Oxygen Species; Thioctic Acid; Urinary Bladder

Topics: Ascorbic Acid; Common Cold; Cystitis; Humans; Substance-Related Disorders

Topics: Ascorbic Acid; Collagen Diseases; Corrinoids; Cystitis; Cystitis, Interstitial; Drug Therapy; Humans; Lupus Erythematosus, Systemic; Pyridoxine; Scleroderma, Systemic; Ulcer; Vitamin B 12

Topics: Ascorbic Acid; Capillaries; Capillary Permeability; Cardiovascular System; Cystitis; Flavones; Flavonoids; Hemorrhage; Humans; Vitamins