See ; Kuecuekoktay, F.S. The animal study protocol was approved by the Committee for Ethical Conduct in the Use of Animals in Experimentation of the State University of Maring (CEUA, n 4422140918). ; Xu, J.; Brigham, K.L. Measurements were performed in 80 distal and 80 proximal tubules per animal. PMC 2011 Nov;26(6):542-5. doi: 10.1177/0267659111410347. RSC Adv. 2021 Sep 20;11(49):31090-31097. doi: 10.1039/d1ra05068k. Dounousi, E.; Papavasiliou, E.; Makedou, A.; Ioannou, K.; Katopodis, K.P. UniveRsitRio Pedro Ernesto UeRJ. permission provided that the original article is clearly cited. One birth defect (ventricular septal defect) and cases of miscarriage have been reported when fluorouracil cream was applied to mucous membrane areas. Side effects, such as veno-occlusive disease [ 23 ], hepatitis, steatosis, steatohepatitis [ 24 ], nephropathy [ 25 ], and chest pain [ 26 ], have been reported in patients after 5-FU treatment. Wigle, T.J.; Tsvetkova, E.V. CLINICAL PHARMACOLOGY) Nursing Mothers: ; Ryan, A.J. Huang, J.; Lucero-Prisno, D.E. Effects of fluorouracil cream applied to actinic keratoses Available online: Marcelino, M.C.D.S. ; Lv, X.F. : conceptualization, methodology, investigation, data curation, writingoriginal draft, writingreview and editing, visualization, project administration, and formal analysis. ; Yuan, J.N. The catabolic metabolism of fluorouracil results in degradation products (e.g., CO PubMed PMID:27443886. It can be recommenced if necessary. ; Neves, C.Q. As treatment is continued, sores and crusts may appear. Topical fluorouracil is used to treat actinic keratosis and superficial basal and squamous cell skin cancers. The medication destroys sun-damaged skin cells, but can also damage normal skin and cause skin irritation. Topical fluorouracil (5-FU) comes as a topical cream, available in 2 strengths. For this purpose, 14 male Wistar rats were divided into treated and control groups and 5-FU was administered at 15 mg/kg (4 consecutive days), 6 mg/kg (4 alternate days), and 15 mg/kg on the 14th day. P53 Dependence of Fas Induction and Acute Apoptosis in Response to 5-Fluorouracil-Leucovorin in Human Colon Carcinoma Cell Lines. Unable to load your collection due to an error, Unable to load your delegates due to an error. You might have one or more of them. This site needs JavaScript to work properly. Riul, S.; Aguillar, O.M. M.C.d.S. 5-Fluorouracil Induced Liver Toxicity in Patients with Colorectal Cancer: Role of Computed Tomography Texture Analysis as a Potential Biomarker. HHS Vulnerability Disclosure, Help The kidneys were less injured compared to the liver and lungs but still showed significant damage. Fluorouracil - Drug Information - Chemocare Intraepidermal carcinoma ulcerating after 3 weeks' treatment, Mild reaction after 10 days treatment to keratoses, Intraepidermal carcinoma ulcerating after 3 weeks' treatment. The diameter of 100 hepatic sinusoids per animal was also measured. Su, L.; Zhang, J.; Gomez, H.; Kellum, J.A. ; Al-Rejaie, S.S. Pharmacological Effects of Marine-Derived Enterococcus Faecium EA9 against Acute Lung Injury and Inflammation in Cecal Ligated and Punctured Septic Rats. A full-face course has been shown to substantially reduce the risk of cutaneous squamous cell carcinoma (SCC) developing in the treated site during the following year. These doses represented 11.7 and 1.95 mg/kg of fluorouracil, respectively. Unauthorized use of these marks is strictly prohibited. Gut Microbiota Modulation of Efficacy and Toxicity of Cancer Chemotherapy and Immunotherapy. Fluorouracil is also occasionally used to treat the following skin conditions: It works best on face and scalp and is less effective on other body sites. ; Risis, S.; Chan, M.H.S. Due to interaction with sunlight, it is best to use fluorouracil cream during the winter months. Ccontrol group; 5-FUtreated group; PTproximal tubules; DTdistal tubules. Wildner, D.; Boxberger, F.; Wein, A.; Wolff, K.; Albrecht, H.; Mnnlein, G.; Janka, R.; Amann, K.; Siebler, J.; Hohenberger, W.; et al. PubMed ; Fluorouracil cream is most often prescribed to clear up actinic keratoses and intraepidermal carcinoma (in situ squamous cell carcinoma). Clinical treatment with 5-FU did not promote inflammatory or oxidative alterations in the kidney samples; however, histological and biochemical changes were observed, including increased serum urea and uric acid. ; Welch, S.A.; Kim, R.B. The Griess reaction was used to indirectly evaluate NO from its by-product, nitrite [. Matsushita, K.; Toyoda, T.; Yamada, T.; Morikawa, T.; Ogawa, K. Comprehensive Expression Analysis of MRNA and MicroRNA for the Investigation of Compensatory Mechanisms in the Rat Kidney after Unilateral Nephrectomy. The nucleotides contained in the kit solution are enzymatically linked to DNA by dUTP, forming an oligomer by digoxigenin. Pediatric Use: Tobar, A.; Ori, Y.; Benchetrit, S.; Milo, G.; Herman-Edelstein, M.; Zingerman, B.; Lev, N.; Gafter, U.; Chagnac, A. Proximal Tubular Hypertrophy and Enlarged Glomerular and Proximal Tubular Urinary Space in Obese Subjects with Proteinuria. [4] Use of either form in pregnancy may harm the baby. These are some of the most common side or important effects: Skin Changes The treatment area will typically cause a burning feeling and, after a few days of treatment, will become red and crusted. 1996-2023 MDPI (Basel, Switzerland) unless otherwise stated. Cardiol J. doi: 10.1016/j.currproblcancer.2021.100746. ; Amagon, K.I. WebThe following side effects are common (occurring in greater than 30%) for patients taking Fluorouracil: Diarrhea Nausea and possible occasional vomiting Mouth sores Poor Efudex (fluorouracil): Skin irritation, burning, redness, dryness, pain, swelling, tenderness, or changes in skin color may occur at the site of application. WebFluorouracil (5-FU) is a commonly used chemotherapeutic agent in many cancers. Use of fluorouracil cream in dermatology, 387172005, 326860000, 292234002, 713977002, 375521000, Fluorouracil wraps, also known as chemowraps, are an in-office. Chemotherapy induced stroke mimic: 5-Fluorouracil encephalopathy fulfilling criteria for tissue plasminogen activator therapy. We had limitations in the analysis of the cytokines IL-1 and IL-10 in the lung tissue due to a lack of material. For oxidative stress analysis, the major lobe of the liver, the left kidney, and the right lung were separated. Fluorouracil | Drugs | BNF | NICE After centrifugation the supernatant was placed on plates, and a solution of Tris-HCl (0.4 M) pH 8.9 and DTNB (5.5-dithiobis 2-nitrobenzoic acid, 10 mM) was added [, The supernatant of each sample was diluted in potassium phosphate buffer (0.2 M, pH: 6.5) and CDNB (1-chloro-2,4-dinitrobenzene) and GSH solutions were added [, The method used was based on Aebi (1984) [, SOD activity was determined by the ability of this enzyme to inhibit the autoxidation of pyrogallol. The analyses were performed using the commercial kit Analisa. Fluorouracil wraps, also known as chemowraps, are an in-office occlusive treatment for extensive field treatment for actinic keratoses and intraepidermal carcinomas. INDIA. At the end of 3 days, the total recovery ranged between 0.48% and 0.94% with an average of 0.76%, indicating that approximately 5.98% of the topical dose was absorbed systemically. Reversible Hepatic Steatosis in Patients Treated with Interferon Alfa-2A and 5-fluorouracil. Blood was collected via cardiac puncture and the plasma was used to evaluate aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, and uric acid. Segments of the major lobe of the liver, the left kidney, and the right lung were separated for the inflammatory analyses. Updated Epidemiology of Gastrointestinal Cancers in East Asia. side effects For more information, please refer to Note that this may not provide an exact translation in all languages, Home 8600 Rockville Pike Nigam, S.; Schewe, T. Phospholipase A2s and Lipid Peroxidation. No special For actinic keratosis, you can expect to use fluorouracil for about 4 weeks, if tolerated. Kim, J.J.; Tannock, I.F. These include: fatigue diarrhea nausea or vomiting The authors thank all the colleagues in the Clinics Hospital from the School of Medicine, University of So Paulo (USP) and Department of Structural and Functional Biology from the State University of Campinas (UNICAMP) for their excellent technical assistance and helpful advice. There have been no reports of overdosage with fluorouracil cream. The levels of GSH and LOOH were significantly reduced in the kidney tissue of 5-FU treated rats, whereas the GST activity was not impaired by the treatment (, In the lung tissue the activity of SOD, CAT, and GST and the levels of GSH decreased significantly in the 5-FU group. Antioxidants. Now that you know how to administer the drug, let's talk about side effects. Store Fluorouracil cream out of reach of pets. ; Li, X.; Tan, L.M. Gelen, V.; engl, E.; Yldrm, S.; Senturk, E.; Tekin, S.; Kkrt, A. After healing, the treated areas are often redder than normal and may feel more sensitive; this redness and sensitivity will gradually fade over a few weeks. CAF: Cytoxan Adriamycin and fluorouracil CEF: Cytoxan Ellence and fluorouracil CMF: Cytoxan methotrexate and fluorouracil FAC: fluorouracil Adriamycin and Cytoxan GET: Gemzar Ellence and Taxol TAC: Taxotere Adriamycin and Cytoxan. ; Sherwood, M.B. Advances and Challenges in Fluoropyrimidine Pharmacogenomics and Pharmacogenetics. ; Verma, M. Dihydropyrimidine Dehydrogenase in the Metabolism of the Anticancer Drugs. The concentration of IL-6 was significantly lower in the 5-FU-treated group and there was no significant difference between the groups in the quantification of IL-10 (, The functional analysis revealed that the serum AST values increased significantly after 5-FU treatment; however, there was no difference in the serum ALT values between the groups (, Most studies conducted with 5-FU use doses higher than the dose used in clinical practice [, In this study, the treatment with 5-FU was performed intraperitoneally [, We demonstrated that the passage of 5-FU through the liver led to functional damage, accessed by elevated serum AST activity (, 5-FU is known to generate reactive species of mitochondrial oxygen through a p53-dependent signaling pathway, which culminates in the release of cytochrome C from mitochondria [, Studies have shown that the presence of oxidative stress and steatosis makes the liver more susceptible to inflammatory reactions [, Oxidative stress and inflammation may be responsible for histological changes in the liver tissue, such as the dilation of sinusoid capillaries [, In the present study we observed that the passage of 5-FU metabolites in the kidneys did not promote oxidative stress damage or inflammation (, Even without inflammation or oxidative stress, alterations were observed in the histological analysis of the kidneys. Poole, C.; Gardiner, J.; Twelves, C.; Johnston, P.; Harper, P.; Cassidy, J.; Monkhouse, J.; Banken, L.; Weidekamm, E.; Reigner, B. future research directions and describes possible research applications. Siegel, R.L. Steatosis and lobular infiltrate were analyzed in 40 random fields per animal, whereas portal infiltrate was analyzed in 20 random fields per animal. Fluorouracil. Since DNA and RNA are essential for cell division and growth, the effect of fluorouracil may be to create a thymine deficiency which provokes unbalanced growth and death of the cell. : resources, data curation, funding acquisition, writingreviewing and editing, and data curation. Fluorouracil exhibited maximum teratogenicity when given to mice as single intraperitoneal injections of 10 to 40 mg/kg on Day 10 or 12 of gestation. Topics AZ The number of cells positive for TUNEL was quantified as the percentage of total cells per animal. The antidigoxigenin antibody was incubated, and antigenantibody binding was detected using immunoperoxidase followed by DAB chromogen (3,3-diaminobenzidine). Fluorouracil treatment is repeated once weekly for 4 to 12 weeks. Novel Strategies to Improve the Anticancer Action of 5-Fluorouracil by Using Drug Delivery Systems. ; Bon-Frauches, A.C.; Silva, A.M.H.P. Bacillus subtilis and in the Drosophila wing-hair spot test. However, in studies with a strain of mouse which is sensitive to the induction of sperm head abnormalities after exposure to a range of chemical mutagens and carcinogens, fluorouracil was inactive at oral doses of 5 to 80 mg/kg/day. For each criterion scores were used for classification. ; Tarnuzzer, R.W. ; Ng, S.C.; Wong, M.C.S. Protracted Venous Infusion 5-Fluorouracil in Combination with Subcutaneous Interleukin-2 and Alpha-Interferon in Patients with Metastatic Renal Cell Cancer: A Phase II Study. WebThis side effects happens in fewer than 1 in 100 people (fewer than 1%). A large percentage of fluorouracil is catabolized by the DPD enzyme. official website and that any information you provide is encrypted Fabiano, L.C. Fluorouracil cream is also contraindicated in patients with known hypersensitivity to any of its components. ; Herreros-Villanueva, M.; Beguiristain, A.; Arenas, J.; et al. , because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue use of the drug, taking into account the importance of the drug to the mother. Cancer Statistics, 2020. If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, the patient should be apprised of the potential hazard to the fetus. Keywords: Reactive Oxygen Species and Programmed Cell Death. Effect of 17 days of fluorouracil cream to actinic keratoses, Actinic keratosis treated with fluorouracil cream, Effects of fluorouracil cream applied to actinic keratoses, Effect of 17 days of fluorouracil cream to actinic keratoses. : methodology and formal analysis. The histological sections of the liver were stained with hematoxylin-eosin (HE) or periodic acid Schiff (PAS). A porous gauze dressing may be applied for cosmetic reasons without increase in reaction. Systemic absorption studies of topically applied fluorouracil have been performed on patients with actinic keratoses using tracer amounts of Costa, D.V.S. Fluorouracil (Topical | Memorial Sloan Kettering Cancer One case of life-threatening systemic toxicity has been reported with the topical use of fluorouracil cream in a patient with DPD enzyme deficiency. Endotoxin-Induced Lung Injury in Mice: Structural, Functional, and Biochemical Responses. ; Singh, D.; Osiagwu, D.D. ; Houghton, J.A. Weinstock MA, Thwin SS, Siegel JA, et al. Fluorouracil Cream USP contains 5% fluorouracil in a vanishing cream base consisting of methylparaben, polysorbate 60, propylene glycol, propylparaben, purified water, stearyl alcohol, and white petrolatum. Therefore, information on its Corbacioglu, S.; Jabbour, E.J. Cancer is the second leading cause of death worldwide. : methodology. Fluorouracil is a pyrimidine analogue that irreversibly binds within a cell to thymidylate synthetase. (, To evaluate the impact of 5-FU treatment in the cell death by apoptosis, TUNEL reaction was performed (, The measurements of the oxidative parameters in the liver showed that treatment with 5-FU induced a significant reduction in the activity of CAT and GST enzymes and in the levels of GSH; however, the activity of SOD was not changed between the groups (, The analysis of the kidney tissue showed a significant increase in the enzymatic activity of CAT and SOD in the treated group. ; Teufel, A.; Thasler, W.E. Alessandrino, F.; Qin, L.; Cruz, G.; Sahu, S.; Rosenthal, M.H. Does EFUDEX have a recommended shelf life? I have two new www.drugs.com. Answers SU suzanne66 18 Nov 2009 Yes, Efudex will have a shelf life and if you look closely you should be able to find it - probably stamped on the bottom of each tube. If it has past the expiry then the safety and efficacy of the cream can not be guaranteed. They should be thrown away. +0 Further Information Efudex ; Portillo, M.P. These raw areas result from the destruction of defective skin cells. Stroke-like presentation makes timely recognition extraordinarily important. Is 5-fluorouracil-induced vasospasm a Kounis syndrome? National Library of Medicine Afterwards, rinse the finger thoroughly with water (or use a glove or cotton bud to apply the cream). Longer may be necessary for the treatment of squamous cell carcinoma in situ. de Andrade, G.L. https://www.cancer.gov/research/areas/global-health#:~:text=Challenges%20in%20Global%20Cancer%20Research,-Addressing%20the%20rising&text=Drugs%20and%20vaccines%20are%20sometimes,less%20effective%20and%20more%20costly. ; Stout, J.R. Creatine in Health and Disease. Fluorouracil cream frequently results in a mild to a severe stinging or burning sensation, depending on the sensitivity of the skin, the severity of the sun damage and how long it has been used for. ; Miller, K.D. ; Freitas, G.B. Before ; de Souza, L.K.M. Fluorouracil (Topical Route) Side Effects - Mayo Clinic Available online: Xie, P.; Mo, J.L. A Feature ; Liu, Z.Q. ; Zhao, L.; Aleman, J.; et al. Thus, the detected alterations in this study can be useful in the search for new adjuvants to attenuate the adverse effects of 5-FU in liver, kidneys, and lungs. You might have one or more of them. Excessive inflammatory reactions to fluorouracil cream, Excessive inflammatory reactions to fluorouracil cream, Books about skin diseasesBooks about the skin The prepared hydrogels were characterized by SEM Tell your doctor if any of these symptoms are severe or do not go away: burning, crusting, redness, discoloration, irritation, pain, itching, rash, Toxicity of 5-Fluorouracil | Multiple Myeloma | Non-Small Cell Lung Cancer (NSCLC) | Small Cell Lung Cancer (SCLC) | Adverse Effects | Bladder Cancer | Brain Cancer | Cervical Cancer | Colorectal Cancer | Endometrial Cancer | Esophageal Cancer | Gastrointestinal Cancer | Genitourinary Cancers | Gynecologic Cancers | Head & Neck A total of 14 male Wistar rats (weight 270.6 8.2 g) were acquired through the Central Animal Facility of the State University of Maring. The remainder was centrifuged at 9000 rpm for 20 min, resulting in a supernatant that was aliquoted separately for catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and lipid hydroperoxides (LOOH) measurements. The widely reported adverse effects are infusion reactions, rash, fever, nausea, vomiting, peripheral neuropathy, and hepatic injury. Chun, Y.S. TUNEL is a dUTP-mediated cutting-edge labeling assay, and the reagents in the kit allow the labeling of the 3OH terminus of the free (exposed) DNA. In an additional study, negligible amounts of labeled material were found in plasma, urine, and expired CO Sorrentino MF, Kim J, Foderaro AE, Truesdell AG. Authors to whom correspondence should be addressed. ; Noronha, A.J. The molecular weight of 5-fluorouracil is 130.08 and the structural formula is: There is evidence that the metabolism of fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. J Oncol Pharm Pract. "A Rodent Model of Human-Dose-Equivalent 5-Fluorouracil: Toxicity in the Liver, Kidneys, and Lungs" Antioxidants 12, no. Fluorouracil (5-FU): Drug Information DermNet Fluorouracil cream is contraindicated in women who are or may become pregnant during therapy. Call your ; Rossi, M.J.; Schultz, G. Five-Minute Treatments with Fluorouracil, Floxuridine, and Mitomycin Have Long-Term Effects on Human Tenons Capsule Fibroblasts. Our data depicted the histological and biochemical alterations resulting from treatment with 5-FU in the liver, kidneys, and lungs of healthy rats submitted to the clinical protocol of 5-FU. ; Madsen, E.L.; Fenger, C.; Poulsen, M.R. 2 after 3 days of treatment with topically applied ; Da Silva Costa, D.V. Because there is some systemic absorption of fluorouracil after topical administration (see The morphometric measurements were performed using Image-Pro Plus-Media Cybernetics image analysis software. People using this drug may get skin reactions where this drug is used. Excessive local inflammatory reaction may cause ulceration, blistering and local swelling. Effects of Resistance Training on Kidney Morphology of Aged Ovariectomized Rats. World Health Organization (WHO). Ten fields were randomly selected from the liver, kidney, and lung slides of each experimental animal. The chemowrap is left in place for 7 days, then removed. WebFLUOROURACIL; DICLOFENAC (flure oh YOOR a sil; dye KLOE fen ak) is a combination of a topical chemotherapy agent and non-steroidal anti-inflammatory drug (NSAID). ; Borges, S.C.; de Souza Carvalho, M.d.G. Single-dose intravenous and intraperitoneal injections of 5-fluorouracil have been reported to kill differentiated spermatogonia and spermatocytes (at 500 mg/kg) and to produce abnormalities in spermatids (at 50 mg/kg) in mice. ; de Freitas, C.D.T. Fluorouracil topical Uses, Side Effects & Warnings Antioxidants 2023, 12, 1005. Use it with care in skin folds (such as those around the nose and lips), since it may irritate more severely in these areas. 2023; 12(5):1005. Occasionally it persists for several months. CONTRAINDICATIONS. Keep it locked up so other people cannot mistakenly use it to treat a rash. Fluorouracil ; Cardoso, V.N. Exposure to ultraviolet rays should be minimized during and immediately following treatment with fluorouracil cream because the intensity of the reaction may be increased. Possible Side Effects of 5-Fluorouracil, Oxaliplatin The edema analyses were performed in 30 random fields per animal (each field with a total of 1451.031 m, We also performed a quantification of hemorrhagic foci, perivascular focal infiltrate, and diffuse infiltrate in the lung parenchyma. Akpinar, B.; Bracht, E.V. For nonparametric data, the comparison between groups was performed using the MannWhitney test. The MPO activity was analyzed after the addition of hydrogen peroxide (H. Citrate buffer (50 mM, pH 4.5) and NAG solution (2.24 mM) were added to the supernatant for the analysis of NAG. government site. Please enable it to take advantage of the complete set of features! Preserve in tight containers. sharing sensitive information, make sure youre on a federal If Fluorouracil Cream USP is applied with the fingers, the hands should be washed immediately afterward. It is a white to practically white crystalline powder which is sparingly soluble in water and slightly soluble in alcohol. On this basis, we examined the effects of the 5-FU clinical treatment on the integrity of the liver, kidneys, and lungs of rats. PM 2.5 Induced Pulmonary Fibrosis in Vivo and in Vitro. Fluorouracil Injection Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. Paper should be a substantial original Article that involves several techniques or approaches, provides an outlook for Fluorouracil produced petite mutations in 5-fluorouracil induced cardiotoxicity: review of the literature. Quimioterapia Antineoplsica: Reviso Da Literatura. These reactions may include burning or stinging, itching, pain, redness, swelling, or bleeding. ; Maifrino, L.B.M. It destroys sun-damaged skin cells, so the skin appears smoother and more youthful. ; Jemal, A. However, it is important to ask your dermatologist if this is appropriate because skin cancers can look very similar and may need surgery or other procedures. ; Charlton, J.R.; Beeman, S.C.; Bennett, K.M. Therefore, information on its side effects when administered at a clinically recommended dose is relevant. About 10 to 20 g of 5-FU is used for each limb. Animal reproduction studies have not been conducted with fluorouracil cream. ; Hellerbrand, C. Analysis of Molecular Mechanisms of 5-Fluorouracil-Induced Steatosis and Inflammation in Vitro and in Mice. precursor immunotherapy. ; Seol, Y.J. NOT FOR OPHTHALMIC, ORAL, Backus, H.H.J. 2023. Long-term treatment with conventional chemotherapy may result in severe systemic side effects. ; Barreto, J.E.F. If fluorouracil cream is applied with the fingers, the hands should be washed immediately afterward. ; Dongsar, T.S. Inflammation and histopathological alterations were also detected. They are a necessary part of treatment and are expected to heal, once the treatment is stopped. ; Li, K.; Lin, X.C. Fluorouracil Cream USP is recommended for the topical treatment of multiple actinic or solar keratoses. Fluorouracil (5FU) | Macmillan Cancer Support [ Ref] Gastrointestinal Very common (10% or more): Stomatitis (75%, when used with fluorouracil), nausea (74%, when used with fluorouracil), diarrhea (66%, when used with fluorouracil), vomiting (46%, when used with fluorouracil), dehydration (when used with fluorouracil) Common (1% to 10%): Constipation (when used with fluorouracil) Learn how we can help. ; Zhang, Y.S. Solar keratoses which do not respond should be biopsied to confirm the diagnosis. Side Effects of Fluorouracil Cream (Fluorouracil Cream), The analysis of the LOOH levels showed an increase in this oxidative stress marker in the lung tissue of treated rats compared to the control group. Only the 5% strength is recommended. The clinical protocol of 5-FU promotes toxicity in the liver, kidneys, and lungs of healthy rats, resulting in different levels of histological and biochemical alterations. For each tissue under study, the assay was standardized using the positive control of apoptosis (TUNEL-positive nuclei treated with DNase I) and the negative control of apoptosis (TUNEL-negative nuclei without dUTP).
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