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Nigerian Journal of Clinical Practice Jul 2023Ischemia-reperfusion (I/R) causes organ dysfunction as a result of the increased formation of various reactive oxygen metabolites, infiltration of inflammatory cells,...
BACKGROUND
Ischemia-reperfusion (I/R) causes organ dysfunction as a result of the increased formation of various reactive oxygen metabolites, infiltration of inflammatory cells, interstitial edema, cellular dysfunction, and tissue death.
AIM
The study aimed to investigate the cytoprotective effect of 2-mercaptoethanesulfonate (MESNA) against tissue damage in rats exposed to carotid ischemia-reperfusion.
MATERIALS AND METHODS
Twenty-four male Wistar albino rats were divided into four groups (n = 6): sham, carotid I/R, I/R + MESNA (75 mg/kg), and I/R + MESNA (150 mg/kg) groups. To induce ischemia in rats, the carotid arteries were ligated with silk sutures for 10 min; the silk suture was then opened, and 1 h reperfusion was done. MESNA (75 and 150 mg/kg) was administered intraperitoneally 30 min before ischemia-reperfusion. Tissue samples from the animals were taken for histological examination, while the serum levels of some biochemical parameters were utilized to evaluate the systemic alterations. ANOVA and Tukey's post hoc tests were applied with a significance level of 5%.
RESULTS
The ischemia-reperfusion-induced tissue damage as evidenced by increase in serum levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, lactate dehydrogenase, and matrix metalloproteinases (MMP-1, -2, -8) was significantly (P < 0.05-0.0001) reversed after treatment with MESNA in a dose-dependent manner. Treatment with MESNA (75 and 150 mg/kg), significantly (P < 0.05-0.0001) decreased the I/R-induced increase in serum tumor necrosis factor-alpha (TNF-α) and Interleukin-1-beta (IL-1 β).
CONCLUSION
The results of this study suggest that MESNA has a protective effect on tissues by suppressing cellular responses to oxidants and inflammatory mediators associated with carotid ischemia-reperfusion.
Topics: Male; Rats; Animals; Mesna; Lung Injury; Rats, Wistar; Brain; Ischemia; Reperfusion; Silk
PubMed: 37635578
DOI: 10.4103/njcp.njcp_654_22 -
Advances in Rheumatology (London,... May 2024To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune... (Review)
Review
Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment.
OBJECTIVE
To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide.
MATERIALS AND METHODS
The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators.
RESULTS
Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered.
CONCLUSION
The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.
Topics: Humans; Cyclophosphamide; Autoimmune Diseases; Cystitis; Mesna; Urinary Bladder Neoplasms; Systemic Vasculitis; Brazil; Immunosuppressive Agents; Hemorrhage; Societies, Medical; Rheumatology
PubMed: 38773538
DOI: 10.1186/s42358-024-00380-0 -
International Journal of Clinical... Oct 2023Cisplatin should be administered with diuretics and Magnesium supplementation under adequate hydration to avoid renal impairment. Patients should be evaluated for eGFR...
Chapter 3: Management of kidney injury caused by cancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.
Cisplatin should be administered with diuretics and Magnesium supplementation under adequate hydration to avoid renal impairment. Patients should be evaluated for eGFR (estimated glomerular filtration rate) during the treatment with pemetrexed, as kidney injury has been reported. Pemetrexed should be administered with caution in patients with a CCr (creatinine clearance) < 45 mL/min. Mesna is used to prevent hemorrhagic cystitis in patients receiving ifosfamide. Febuxostat is effective in avoiding hyperuricemia induced by TLS (tumor lysis syndrome). Preventative rasburicase is recommended in high-risk cases of TLS. Thrombotic microangiopathy could be triggered by anticancer drugs and there is no evidence of efficacy of plasma exchange therapy. When proteinuria occurs during treatment with anti-angiogenic agents or multi-kinase inhibitors, dose reductions or interruptions based on grading should be considered. Grade 3 proteinuria and renal dysfunction require urgent intervention, including drug interruption or withdrawal, and referral to a nephrologist should be considered. The first-line drugs used for blood pressure elevation due to anti-angiogenic agents are ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin receptor blockers). The protein binding of drugs and their pharmacokinetics are considerably altered in patients with hypoalbuminemia. The clearance of rituximab is increased in patients with proteinuria, and the correlation with urinary IgG suggests similar pharmacokinetic changes when using other antibody drugs. AIN (acute interstitial nephritis) is the most common cause of ICI (immune checkpoint inhibitor)-related kidney injury that is often treated with steroids. The need for renal biopsy in patients with kidney injury that occurs during treatment with ICI remains controversial.
PubMed: 37453935
DOI: 10.1007/s10147-023-02382-2 -
Analytical and Bioanalytical Chemistry Nov 2023In optical biosensing, analyte-independent factors such as autofluorescence interference and excitation source fluctuation decrease the sensitivity and accuracy. Herein,...
In optical biosensing, analyte-independent factors such as autofluorescence interference and excitation source fluctuation decrease the sensitivity and accuracy. Herein, we reported a bimodal persistent luminescence strategy to design dual-emissive persistent luminescence nanoparticles (PLNPs) with built-in self-calibration to preclude interference from analyte-independent factors in biosensing. As a proof of concept, ZnGaO:Cr PLNPs with emissions at both 490 nm and 695 nm were designed. The I/I ratio of ZnGaO:Cr was readily adjusted by simply changing the doping concentration of Cr. The ZnGaO:Cr PLNPs were employed for the ratiometric detection of urinary mesna. A good linear relationship between the I/I ratio of ZnGaO:Cr-based nanoprobe and the concentration of mesna was obtained in the range of 0-40 μM. The limit of detection was about 0.40 μM. Results showed that autofluorescence interference from urine was totally eliminated by collecting the persistent luminescence signal of ZnGaO:Cr after excitation ceased. Moreover, the built-in self-calibration feature of the ratiometric ZnGaO:Cr PLNPs efficiently suppressed the interference from fluctuations in instrumental parameters during urinary mesna detection. The recovery rates of mesna in the spiked urine samples are in the range of 99.1~109.0%, showing the reliability of the ratiometric ZnGaO:Cr PLNPs in urinary mesna detection. ZnGaO:Cr can further be expanded to the detection of other analytes in complex matrices. This study may open new opportunities for the design of dual-emissive PLNPs with tunable ratios of emission intensity, and it can further promote the applications of optical biosensing in disease diagnosis, food safety, and environmental monitoring.
PubMed: 37733257
DOI: 10.1007/s00216-023-04949-4 -
Diabetes, Obesity & Metabolism Nov 2023To investigate whether mesna-sodium-2-mercaptoethane sulfonate) can reduce diet-induced fat gain in mice, and to assess the safety of single ascending mesna doses in...
AIM
To investigate whether mesna-sodium-2-mercaptoethane sulfonate) can reduce diet-induced fat gain in mice, and to assess the safety of single ascending mesna doses in humans to find the dose associated with lowering of plasma tCys by at least 30%.
METHODS
C3H/HeH mice were shifted to a high-fat diet ± mesna in drinking water; body composition was measured at weeks 0, 2 and 4. In an open, phase I, single ascending dose study, oral mesna (400, 800, 1200, 1600 mg) was administered to 17 men with overweight or obesity. Mesna and tCys concentrations were measured repeatedly for a duration of 48 hours postdosing in plasma, as well as in 24-hour urine.
RESULTS
Compared with controls, mesna-treated mice had lower tCys and lower estimated mean fat mass gain from baseline (week 2: 4.54 ± 0.40 vs. 6.52 ± 0.36 g; week 4: 6.95 ± 0.35 vs. 8.19 ± 0.34 g; P = .002), but similar lean mass gain. In men with overweight, mesna doses of 400-1600 mg showed dose linearity and were well tolerated. Mesna doses of 800 mg or higher decreased plasma tCys by 30% or more at nadir (4h post-dosing). With increasing mesna dose, tCys AUC decreased (P < .001), and urine tCys excretion increased (P = .004).
CONCLUSIONS
Mesna reduces diet-induced fat gain in mice. In men with overweight, single oral doses of mesna (800-1600 mg) were well tolerated and lowered plasma tCys efficiently. The effect of sustained tCys-lowering by repeated mesna administration on weight loss in humans deserves investigation.
Topics: Humans; Male; Cysteine; Mesna; Mice, Inbred C3H; Obesity; Overweight; Animals; Mice; Clinical Trials, Phase I as Topic
PubMed: 37435697
DOI: 10.1111/dom.15210 -
BMJ Case Reports Apr 2024A man in his 60s presented to an outside hospital with persistent groin pain and a scrotal mass which was thought to be a recurrent hernia. Three months after initial...
A man in his 60s presented to an outside hospital with persistent groin pain and a scrotal mass which was thought to be a recurrent hernia. Three months after initial presentation, the patient was found to have dedifferentiated liposarcoma (LPS) of the spermatic cord. LPS of the spermatic cord is a rare entity; however, clinicians should have LPS on the differential diagnosis especially in men with recurrent scrotal pain and mass. If unrecognised, LPS is associated with a high degree of morbidity and mortality. LPS can be subdivided into well-differentiated LPS, dedifferentiated LPS, myxoid LPS and pleomorphic LPS. In patients with advanced or metastatic LPS, chemotherapy consisting of Adriamycin, ifosfamide and mesna is used despite LPS being relatively chemoresistant. Therapies inhibiting mouse double minute 2 homologue, an oncoprotein that is a negative regulator of the tumour suppressor p53, appear to be promising in preclinical trials.
Topics: Male; Animals; Mice; Humans; Adult; Spermatic Cord; Lipopolysaccharides; Liposarcoma; Liposarcoma, Myxoid; Lipoma; Pain; Genital Neoplasms, Male
PubMed: 38627046
DOI: 10.1136/bcr-2023-258954 -
Naunyn-Schmiedeberg's Archives of... Aug 2023Acrolein is the main toxic metabolite of ifosfamide (IFO) that causes urothelial damage by oxidative stress and inflammation. Here, we investigate the molecular...
Acrolein is the main toxic metabolite of ifosfamide (IFO) that causes urothelial damage by oxidative stress and inflammation. Here, we investigate the molecular mechanism of action of gingerols, Zingiber officinale bioactive molecules, as an alternative treatment for ifosfamide-induced hemorrhagic cystitis. Female Swiss mice were randomly divided into 5 groups: control; IFO; IFO + Mesna; and IFO + [8]- or [10]-gingerol. Mesna (80 mg/kg, i.p.) was given 5 min before, 4 and 8 h after IFO (400mg/kg, i.p.). Gingerols (25 mg/kg, p.o.) were given 1 h before and 4 and 8 h after IFO. Animals were euthanized 12 h after IFO injection. Bladders were submitted to macroscopic and histological evaluation. Oxidative stress and inflammation were assessed by malondialdehyde (MDA) or myeloperoxidase assays, respectively. mRNA gene expression was performed to evaluate mesna and gingerols mechanisms of action. Mesna was able to protect bladder tissue by activating NF-κB and NrF2 pathways. However, we demonstrated that gingerols acted as an antioxidant and anti-inflammatory agent stimulating the expression of IL-10, which intracellularly activates JAK/STAT/FOXO signaling pathway.
Topics: Mice; Animals; Female; Ifosfamide; Mesna; Interleukin-10; Cystitis; Hemorrhage; Inflammation; Signal Transduction
PubMed: 36843129
DOI: 10.1007/s00210-023-02436-2 -
Otolaryngologia Polska = the Polish... Jul 2023<b>Introduction:</b> Surgery is still the method of choice in chronic otitis media with cholesteatoma. Except for some specific clinical situations, classic...
<b>Introduction:</b> Surgery is still the method of choice in chronic otitis media with cholesteatoma. Except for some specific clinical situations, classic canal wall up technique (CWU), remains a gold standard as a primary treatment in most departments. Unfortunately, the risk of recurrence in such an approach is estimated at 9 to even 70%. This fact prompts researchers to look for ways to reduce those unfavourable statistics. One of the recognized methods supporting the removal of cholesteatoma is the intraoperative use of mesna (sodium 2-mercaptoethanesulfonate). This synthetic sulphur compound disrupts disulfide bridges in polypeptide chains, thanks to which it facilitates matrix preparation.</br></br> <b>Aim:</b> To evaluate the effect of intraoperative use of mesna on the treatment outcomes in patients with chronic otitis media with cholesteatoma operated on by means of the canal wall up technique (CWU).</br></br> <b>Material and methods:</b> 459 surgical reports of patients with middle ear cholesteatoma were analyzed. In total, 52 adult patients with no history of previous ear surgery operated on by means of the CWU technique by the same experienced otosurgeon with all follow-up data available were included in the study. Twenty-six were operated on with the use of mesna (mesna group) and 26 by means of the classic CWU technique (control / no-mesna group). There were 28 women and 24 men with a mean age of 41 years.</br></br> <b>Main Outcome Measure(s):</b> Postoperative hearing results and cholesteatoma recidivism rate.</br></br> <b>Results:</b> Overall recidivism rate was 21.15 %. It was higher in the no-mesna (26.9%) than in the mesna group (15.4%) - although the outcomes were better in the mesna group, the difference was not statistically significant (P = 0.49715). Hearing gain was better in the mesna than in the no-mesna group (10 dB vs 7 dB), but the difference was not statistically significant (P = 0.20089).</br></br> <b>Conclusions:</b> Our preliminary results show that mesna reduces recidivism rates in patients with cholesteatoma. Further study with the analysis of a larger group of patients is needed to prove it statistically.
PubMed: 37772375
DOI: 10.5604/01.3001.0016.3415 -
The Journal of Pharmacology and... Jan 2024Inhalation of high levels of sulfur mustard (SM), a potent vesicating and alkylating agent used in chemical warfare, results in acutely lethal pulmonary damage. Sodium...
Inhalation of high levels of sulfur mustard (SM), a potent vesicating and alkylating agent used in chemical warfare, results in acutely lethal pulmonary damage. Sodium 2-mercaptoethane sulfonate (mesna) is an organosulfur compound that is currently Food and Drug Administration (FDA)-approved for decreasing the toxicity of mustard-derived chemotherapeutic alkylating agents like ifosfamide and cyclophosphamide. The nucleophilic thiol of mesna is a suitable reactant for the neutralization of the electrophilic group of toxic mustard intermediates. In a rat model of SM inhalation, treatment with mesna (three doses: 300 mg/kg intraperitoneally 20 minutes, 4 hours, and 8 hours postexposure) afforded 74% survival at 48 hours, compared with 0% survival at less than 17 hours in the untreated and vehicle-treated control groups. Protection from cardiopulmonary failure by mesna was demonstrated by improved peripheral oxygen saturation and increased heart rate through 48 hours. Additionally, mesna normalized arterial pH and pACO Airway fibrin cast formation was decreased by more than 66% in the mesna-treated group at 9 hour after exposure compared with the vehicle group. Finally, analysis of mixtures of a mustard agent and mesna by a 5,5'-dithiobis(2-nitrobenzoic acid) assay and high performance liquid chromatography tandem mass spectrometry demonstrate a direct reaction between the compounds. This study provides evidence that mesna is an efficacious, inexpensive, FDA-approved candidate antidote for SM exposure. SIGNIFICANCE STATEMENT: Despite the use of sulfur mustard (SM) as a chemical weapon for over 100 years, an ideal drug candidate for treatment after real-world exposure situations has not yet been identified. Utilizing a uniformly lethal animal model, the results of the present study demonstrate that sodium 2-mercaptoethane sulfonate is a promising candidate for repurposing as an antidote, decreasing airway obstruction and improving pulmonary gas exchange, tissue oxygen delivery, and survival following high level SM inhalation exposure, and warrants further consideration.
Topics: Rats; Animals; Mustard Gas; Mesna; Antidotes; Lung; Sodium; Chemical Warfare Agents
PubMed: 37541763
DOI: 10.1124/jpet.123.001683