Animal groups were pretreated as follows, except for group I (Sham) which did not receive any treatment: Group II, the negative control (NC), were pretreated with vehicle (Tween-saline), and group III, the positive control, were treated with sodium 2-mercaptoethane sulfonate (Mesna) at 80 mg/kg intraperitoneally, three times at intervals of 4 h because its plasma half-life is short (approximately 1.5 h). There were no viral inclusions or granulomas. A: Duodenum; B: Descending colon. Klippel JH, Decker JL et al. Post-mortem histopathology. Before In this assay, Evans blue (25 mg/kg) was intravenously administered via caudal plexus 30 min before euthanasia. Abrupt changes in the microbiome may result in excessive generation of reactive oxygen species in the epithelium, thereby upregulating pro-inflammatory cytokines[7]. Before Results were expressed in nmol/g of bladder tissue. Data are expressed as mean SEM (n = 6) of the ratio of bladder wet weight to animal mass after the experimental protocol (mg/20 g of animal weight). 8600 Rockville Pike Interestingly, animals pretreated with IPG at a dose of 25 mg/kg showed significantly decreased TNF- (88.72%) and IL-1 (62.87%) levels when compared with the negative control group (p < 0.05). the contents by NLM or the National Institutes of Health. Bleeding time, clotting time and prothrombin time were normal. Stringer AM, Al-Dasooqi N, Bowen JM, Tan TH, Radzuan M, Logan RM, Mayo B, Keefe DM, Gibson RJ. Computed tomography of the abdomen showed diffuse mural thickening of the small and large bowel. This finding is compatible with the pattern of anti-inflammatory activity demonstrated by phenolic compounds with a gallic acid-related chemical structure found in the literature [41]. Therefore, the search for novel uroprotective agents is required for managing this condition. Representative histological alterations of the bladders of the mice of different groups. The first look at the 'middle aged Love Island' set has been released, which has already been nicknamed the 'Viagra House' by locals after single parents searched for love (DG) Test groups IFOS + IPG (6.25, 12.5, 25, or 50 mg/kg, respectively). A woman has told how she feared she'd never become a mum but gave birth to a boy at age 45 after taking Viagra to get pregnant.. Carin Rockind, 48, welcomed a "miracle" baby after trying to have a . To quantify blood loss in the bladder tissue, a colorimetric test was used. Afterwards, the samples were embedded in liquid paraffin, and sectioned using a 4 m-thick microtome. Intrahippocampal infusion of a cyclooxygenase-2 inhibitor attenuates memory acquisition in rats. The arrows indicate: hemorrhage () and nucleated polymorphs () (Hematoxylin and Eosin staining, 400 magnification). The present study provided evidence that IPG exerts anti-inflammatory and antioxidant activities which modulate the hallmarks underlying hemorrhagic cystitis, as it reduced the levels of TNF-, IL-1, MDA, and C-reactive protein, as well as increasing SOD levels and reducing edema and hemorrhage. A Prospective randomized study. Similar changes, but less severe were seen in sections of ascending and transverse colon. The high power view of small bowel shows focal full thickness mucosal ulceration with inflamed granulation tissue and preservation of the muscularis mucosae (arrow); B: Colon. We considered the diagnosis of a severe neutropenic typhilitis secondary to cyclophosphamide. Un programa que dej de tener gracia cuando se. Tumor necrosis factor-alfa and interleukin-1beta mediate the production of nitric oxide involved in the pathogenesis of ifosfamide induced hemorrhagic cystitis in mice. Prophylactic antibiotics, antivirals and antifungals, anti-diarrhoeals, intravenous fluids and electrolytes, total parenteral nutrition, glucocorticoids and infliximab. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. Mills K.A., Chess-Williams R., McDermott C. Novel insights into the mechanism of cyclophosphamide-induced bladder toxicity: Chloroacetaldehydes contribution to urothelial dysfunction in vitro. At the same time, an absorbanceconcentration curve was plotted. ; data curation, L.S.A.d.O., B.P.d.S.N. Oxidative stress in aging: Theoretical outcomes and clinical evidences in humans. 1. During cyclophosphamide treatment, plenty of oral fluids, bladder irrigation and frequent voiding are recommended since-these reduce the time of contact of acrolein with the bladder mucosa, thereby minimising the chances of cystitis. Received 2022 Mar 22; Accepted 2022 May 8. After euthanasia, bladders were removed, emptied, and fixed in 10% buffered formalin (pH~7.2). Conflict-of-interest statement: The authors have no conflicts of interest or funding from any organisation to disclose. Infliximab was administered as empirical therapy without significant clinical or endoscopic improvement. However, this drug presents some dose-dependent side effects. government site. Data were compared with the negative control (Tween/saline) by one-way analysis of variance (ANOVA), followed by the Bonferroni test; * p < 0.05. Repeat colonic biopsies showed regenerative mucosal changes. Data are expressed in U of SOD per g of protein, as mean SEM (n = 6). Acute haemorrhagic cystitis is a troublesome complication of high dose cyclophosphamide administration. (A) Group Sham received only saline as a placebo, without induction of hemorrhagic cystitis. The results were expressed as mean SEM. Author contributions: Yang LS wrote the paper; Yang LS and Cameron K collected the clinical data; Papaluca T, Basnayake C, Goodman D, Demediuk B, Bell SJ and Thompson AJ were the treating team and supervised the manuscript writing; Jackett L and McKelvie P provided the figures. Salazar J., Martnez M.S., Chvez-Castillo M., Nez V., Aez R., Torres Y., Toledo A., Chacn M., Silva C., Pacheco R., et al. Das K., Samanta L., Chainy G.B.D. Similarly, pretreatment with IPG attenuated the apparent lesions, especially at doses of 12.5 and 25 mg/kg (Figure 3E,F). The animals were obtained from the Central Bioterium of the Federal University of Piau. The results showed that pretreatment with IPG significantly decreased levels of MDA in the bladder tissue, compared to the experimental model of hemorrhagic cystitis. The activity of superoxide dismutase was determined following a modified spectrophotometric assay [23]. ); rb.moc.oohay@asuosed_oaimad (D.P.d.S. 1Medicinal Plants Research Center, Federal University of Piau, Av. By day 4, she became thrombocytopenic and . and transmitted securely. Over the next one week, platelet count rose to over 100,000/cmm, however, gross haematuria continued. Due to the unusual presentation and scarcity of similar case reports in literature, this case can be a diagnostic and therapeutic challenge. (B) IFOS group. Conceptualization, F.R.d.C.A. This does not seem likely as there was evidence of mucosal regeneration on repeat biopsies and at postmortem This would be the first case of this scenario occurring with cyclophosphamide, which is used widely for treatment of inflammatory bowel disease including patients with extensive ulceration and for patients with vasculitis of the gastrointestinal tract. Integr. The choice of the above images was based on the selection of a bladder considered the median among each group. Cyclophosphamide was initially reduced to 50 mg daily and then ceased in setting of potential infectious pathology. Effects of IPG on histopathological changes in bladder tissues of mice with ifosfamide-induced hemorrhagic cystitis. As a library, NLM provides access to scientific literature. He received 2 cycles of induction chemotherapy with duanorubicin, vincristine and L-asaparaginase. Severe gastrointestinal toxicity is not commonly associated with cyclophosphamide and data on the association between cyclophosphamide and enteropathy are scarce. Regarding the effects of IPG, the results showed that the administration of IPG at the doses of 12.5 and 25 mg/kg significantly decreased the wet bladder weight, by 29.73% and 36.86%, respectively, when compared with the negative control. A 60-year-old male was diagnosed with histologically confirmed glomerulonephritis secondary to anti-neutrophil cytoplasmic antibody -positive microscopic polyangiitis, following investigations for elevated creatinine on routine blood test. The aim of this study was to evaluate the protective effect of isopropyl gallate (IPG) against ifosfamide (IFOS)-induced hemorrhagic cystitis in mice. Carin Rockind, Josh Klur and Shay. The case highlights that late and severe haemorrhagic cystitis can develop even when cyclophasphamide has not been given in high doses. On examination, he was found to have pallor, generalized lymphadenopathy and hepatosplenomegaly. Hemorrhagic cystitis (HC) is a symptom complex that refers to bleeding caused by an irritation of the bladder mucosa that can be of insidious or rapid onset. These cases can be challenging problems for the urologist and a source of substantial morbidity and sometimes mortality for the patients. The .gov means its official. Tissue PCR and cultures for infective causes were negative ante-mortem but prolonged immunosuppression is associated with high risks of secondary infection. 06:54, 6 JUN 2023. Physical and chemical parameters of gallic acid showed: White solid; MP = 1451416 C; TLC (1:1 hexane/EtOAc), Rf = 0.87; 1H-NMR (400 MHz, DMSO-d6), H 9.25 (s, 2H, m-OH), 8.89 (s, 1H, p-OH), 6.94 (s, 2H, H-2, H-6), 5.02 (sept, 1H, H-1), 1.25 (d, J = 4 Hz, 6H, H-2, H-3); 13C-NMR (100 MHz, DMSO-d6), C 165.4, 145.6, 138.4, 120.1, 108.6, 67.3, 21.9. sharing sensitive information, make sure youre on a federal The site is secure. Cyclophosphamide is an alkylating Urinary Tract and - HRenalmorrhagic Toxicity cystitis, pyelitis, ureteritis, and r.hematuria Exclude orcaninary c occurrect tract any urobstructions prior5.2). four hours after oral pretreatment with IPG (6.25, 12.5, 25, and 50 mg/kg) or saline (vehicle). Euthanasia procedures were performed intraperitoneally using an anesthetic overdose (sodium thiopental 150 mg/kg and lidocaine 10 mg/kg), under the supervision of the veterinarian Adeline de Andrade Carvalho (CRMV-PI 866-VP) in accordance with CONCEA guidelines in paragraph 1, Article 14 of CFMV Resolution No. A 45-year-old woman who feared she'd never become a mum welcomed a "miracle" baby - after inserting Viagra to fall pregnant. and F.d.A.O. Moreover, Mesna can promote some adverse effects, such as allergic reactions, dermatosis, and hypersensitivity in the skin [8]. Nossa Senhora de Ftima s/n, Teresina 64049-550, Brazil; moc.liamg@onaylos.sacul (L.S.A.d.O. He was treated in hospital with intravenous methylprednisolone (500 mg daily) and oral cyclophosphamide (100 mg daily) for three days. Hemorrhagic cystitis after single doses of cyclophosphamide has been reported. ); moc.liamg@sevlacnoglogirdorforp (R.L.G.G. Other available literature mainly describes the therapeutic use of pulse cyclophosphamide in gastrointestinal vasculitis and refractory inflammatory bowel disease. and F.d.A.O. The .gov means its official. After 30 min, a single dose of ifosfamide (400 mg/kg, i.p.) The hemorrhagic cystitis induced by IFOS administration also caused a marked increase of TNF- and IL-1 cytokines when compared with the Sham group. REFERENCES Volume 105, Issue 7 April 2010 Cyclophosphamide toxicity. Figure 8 shows that the administration of ifosfamide led to a significant increase in the levels of MDA in the urinary bladder when compared with the Sham group. The findings of this case report were similar to our case, but confined to the colon. In the literature, it is possible to find a tendency towards natural products as alternative safe therapies to reduce the urotoxicity caused using oxazaphosphorines [10,11,12,13]. His wife had had similar symptoms recently. The patient developed large volume watery diarrhea, up to eight liters per day. The .gov means its official. In: Tierney LM, McPhce SJ, Papadaki MA, editors. sharing sensitive information, make sure youre on a federal Correspondence to: Linda S Yang, MBBS, Department of Gastroenterology, St. Vincents Hospital, 41 Victoria Pde, Fitzroy, Victoria 3065, Australia. However, the etiology of this devastating complication is associated with the metabolism of oxazaphosphorine, which leads to the biosynthesis of highly reactive metabolites, such as acrolein and chloroacetaldehyde [25]. The rectum was relatively spared. Chemotherapy-induced hemorrhagic cystitis: Pathogenesis, pharmacological approaches and new insights. The natural flavonoid luteolin (LUT) has significant anti-inflammatory and antioxidant properties, but its protective effect on cyclophosphamide (CYP)-induced bladder toxicity has yet to be evaluated. Data were compared with the negative control (Tween/saline), by one-way analysis of variance (ANOVA), followed by the Bonferroni test; * p < 0.05, ** p < 0.001. Data are expressed in mg of CRP per liter of serum, as mean SEM (n = 6). [15], several evidences are reported on the use of gallic acid in the treatment of microalbuminuria, and selective cytotoxicity against a variety of cell tumors. Silva Junior R.N.C., Fialho S.E.M., Assuno A.K.M., Machado J.L., Arruda D., Furtado P.G.R., Gonalves F.A., Nascimento F.R.F. Interestingly, IPG increased SOD activity (89.27%) and reduced MDA levels (35.53%), as well as displayed anti-inflammatory activity by decreasing TNF- (88.77%), IL-1 (62.87%), and C-reactive protein (56.41%) levels. Attempts have been made to alleviate the adverse effects of IFOS on the bladder mucosa. It is widely known that the oxazaphosphorine-induced hemorrhagic cystitis is the marked presence of a massive extravasation of mature red cells and reticulocytes, characterized by the presence of hematuria [37,38]. Moreover, prophylactic antimicrobial therapy should be considered to prevent significant morbidity or mortality. On the other hand, IPG at doses of 6.25 or 50 mg/kg failed to inhibit the damage caused by IFOS. ; visualization, M.L., A.D. and D.D.R.A. A urinary metabolite of cyclophosphamide, acrolein, is believed to be responsible for hemorrhagic cystitis.1 The best treatment for hemorrhagic cystitis is still unknown. [17], which summarizes the IPG-induced pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Among them, isopropyl gallate (IPG) is potentially useful in the development of new anti-inflammatory agents, as reported by the recent review carried out by Bai et al. Bai J., Zhang Y., Tang C., Hou Y., Ai X., Chen X., Zhang Y., Wang X., Meng X. Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. 8600 Rockville Pike An official website of the United States government. ); moc.liamtoh@rs.leuqararas (S.R.d.M.B. Then, 100 microliters of homogenate were added to 1110 L of phosphate buffer, 75 L of L-methionine (20 mM), 40 L of Triton X-100 (1% v/v), 75 L of hydroxylamine chloride (10 mM), and 100 L of EDTA (50 M). Sections from all lobes of the lungs revealed changes of diffuse alveolar damage (shock lung) and metastatic pulmonary calcification. official website and that any information you provide is encrypted and L.G.d.N. The low oral bioavailability of gallic acid has prompted research on the development of synthetic-derived compounds. Total leucocyte count was 5000/cmm polymorphs 65 per cent lymphocytes 30 per cent, monocytes 2 per cent and eosinophils 3 per cent. These profile changes are characteristic of a phenomenon called hormesis, described as an effect of some substances which show biphasic dose responses displaying a U shape [34]. official website and that any information you provide is encrypted Effect of IPG on TNF- (A) and IL-1 (B) levels in the bladder tissue of animals with ifosfamide-induced hemorrhagic cystitis. Informed consent statement: A written informed consent was waived by the Institutional Review Board given this case report presents no more than minimal risk to the patient involved. Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: A data-driven review. Besides, a loss of activity with lower and higher doses was observed, whereby 6.25 and 50 mg/kg of IPG did not show any activity on this parameter. 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An absorbanceconcentration curve was plotted and electrolytes, total parenteral nutrition, glucocorticoids and infliximab Federal University of Piau Av!, Federal University of Piau, Av be a diagnostic and therapeutic challenge per.! Case report were similar to our case, but less severe were seen in sections of ascending and transverse.! Of gallic acid has prompted Research on the association between cyclophosphamide and enteropathy are scarce cytokines when compared the... The activity of superoxide dismutase was determined following a modified spectrophotometric assay [ 23 ] cytokines when with.
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