{
    "abstract": "Cisplatin (CIS) is a potent chemotherapeutic agent primarily used to treat hematologic malignancies and solid tumors, including lymphomas, sarcomas, and some carcinomas. Patients receiving this treatment for tumors outside the nervous system develop cognitive impairment. Alterations in the kynurenine pathway (KP) following CIS treatment suggest that certain KP metabolites may cross the blood-brain barrier, leading to increased production of the neuromodulator kynurenic acid (KYNA), which is associated with cognitive impairment. This study aimed to evaluate the effects of modulating brain KYNA levels by the administration of N-acetylcysteine (NAC), an inhibitor of kynurenine aminotransferase II (KATII), an enzyme responsible for KYNA biosynthesis on the cognitive and neuromuscular deficits induced by CIS. Female Wistar rats were divided into four groups: control, NAC (300 mg/day/8 days), CIS (3 mg/kg i.p/5 days), and NAC + CIS (both treatments co-administered in parallel). Seven days after the last CIS administration, cognitive performance, muscle strength, brain KYNA levels, KATII activity, and brain tissue redox profile (lipid peroxidation and oxidized/reduced glutathione (GSH/GSSG) ratio) were assessed. CIS did not affect short-term memory but induced long-term memory deficits and reduced muscle strength, effects which were prevented by NAC co-administration. CIS decreased the GSH/GSSG ratio and the number of cells in the brain cortex while it increased lipid peroxidation, KYNA levels, and marginal KATII activity. All these effects were attenuated by the co-administration of NAC. These findings suggest that NAC mitigates the side effects of CIS, such as chemo-brain and muscle weakness, by improving the redox imbalance and modulating KYNA levels by limiting its non-enzymatic production by reactive oxygen species (ROS).",
    "authors": [
        {
            "affiliation": "Doctorado en Ciencias Biol\u00f3gicas, Centro Tlaxcala Biolog\u00eda de la Conducta, Universidad Aut\u00f3noma de Tlaxcala, Tlaxcala 90070, Mexico.\nNeurochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.\nLaboratorio de Neurobiolog\u00eda Conductual, Departamento de Fisiolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico.",
            "firstname": "Teminijesu",
            "initials": "T",
            "lastname": "Dorcas Aremu"
        },
        {
            "affiliation": "Neurochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.",
            "firstname": "Daniela",
            "initials": "D",
            "lastname": "Ram\u00edrez Ortega"
        },
        {
            "affiliation": "Neurochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.",
            "firstname": "Tonali",
            "initials": "T",
            "lastname": "Blanco Ayala"
        },
        {
            "affiliation": "Neurochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.",
            "firstname": "Dinora Fabiola",
            "initials": "DF",
            "lastname": "Gonz\u00e1lez Esquivel"
        },
        {
            "affiliation": "Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.",
            "firstname": "Benjam\u00edn",
            "initials": "B",
            "lastname": "Pineda"
        },
        {
            "affiliation": "Department of Mathematics, Faculty of Sciences, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico.",
            "firstname": "Gonzalo",
            "initials": "G",
            "lastname": "P\u00e9rez de la Cruz"
        },
        {
            "affiliation": "Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.",
            "firstname": "Alel\u00ed",
            "initials": "A",
            "lastname": "Salazar"
        },
        {
            "affiliation": "Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.\nDepartamento de Inmunolog\u00eda, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Manuel Carpio, Plutarco El\u00edas Calles, Miguel Hidalgo, Mexico City 11350, Mexico.",
            "firstname": "Itamar",
            "initials": "I",
            "lastname": "Flores"
        },
        {
            "affiliation": "Neurochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.",
            "firstname": "Karla F",
            "initials": "KF",
            "lastname": "Meza-Sosa"
        },
        {
            "affiliation": "Neuromuscular Diseases Laboratory, National Institute of Rehabilitation \"Luis Guillermo Ibarra Ibarra\", Mexico City 14389, Mexico.",
            "firstname": "Laura",
            "initials": "L",
            "lastname": "S\u00e1nchez Chapul"
        },
        {
            "affiliation": "Cell Reprogramming Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.",
            "firstname": "Edgar",
            "initials": "E",
            "lastname": "Rangel-L\u00f3pez"
        },
        {
            "affiliation": "Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, M\u00e9xico City 04530, Mexico.",
            "firstname": "Sa\u00fal",
            "initials": "S",
            "lastname": "G\u00f3mez-Manzo"
        },
        {
            "affiliation": "Neuroimmunology Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.",
            "firstname": "Adri\u00e1n",
            "initials": "A",
            "lastname": "M\u00e1rquez Navarro"
        },
        {
            "affiliation": "Doctorado en Ciencias Biol\u00f3gicas, Centro Tlaxcala Biolog\u00eda de la Conducta, Universidad Aut\u00f3noma de Tlaxcala, Tlaxcala 90070, Mexico.",
            "firstname": "Gabriel",
            "initials": "G",
            "lastname": "Rold\u00e1n Rold\u00e1n"
        },
        {
            "affiliation": "Neurochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \"Manuel Velasco Su\u00e1rez\", Mexico City 14269, Mexico.",
            "firstname": "Ver\u00f3nica",
            "initials": "V",
            "lastname": "P\u00e9rez de la Cruz"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.3390/cells13231989\n10.1093/carcin/bgp263\n10.1038/nrc1781\n10.7150/ijms.3635\n10.1007/s13235-023-00529-4\n10.2174/1570159X18666200221113842\n10.1016/j.ctrv.2017.09.010\n10.2478/raon-2019-0018\n10.1016/j.ejphar.2014.07.025\n10.2174/0929867033368484\n10.3390/ijms21041242\n10.1007/s12640-020-00315-9\n10.1186/s40360-023-00651-4\n10.3390/ijms222312697\n10.15252/emmm.202012075\n10.1016/j.neulet.2016.11.028\n10.1155/2017/1315378\n10.1586/14737175.2015.1049999\n10.1016/j.neuropharm.2016.03.013\n10.1016/j.neuropharm.2014.03.004\n10.1016/j.jsb.2014.01.009\n10.1111/cns.13768\n10.1155/2018/5272741\n10.3389/fncel.2015.00178\n10.1038/npp.2011.127\n10.1038/nrn3257\n10.1111/j.1460-9568.2008.06594.x\n10.1046/j.0953-816x.2001.01592.x\n10.1111/j.1471-4159.2005.03134.x\n10.1016/j.nlm.2020.107282\n10.1523/JNEUROSCI.1107-14.2014\n10.3390/antiox10020147\n10.1016/j.jns.2012.08.005\n10.3390/biom10040571\n10.3390/antiox8050111\n10.1016/j.chembiol.2018.01.011\n10.3390/antiox12122035\n10.1016/j.neuroscience.2020.07.049\n10.1016/j.hest.2020.09.001\n10.1523/JNEUROSCI.2714-16.2016\n10.3390/antiox10071116\n10.1007/s11356-019-04780-4\n10.1021/acs.chemrestox.1c00110\n10.1155/2011/843019\n10.1002/14651858.CD005228.pub4\n10.1186/s13041-015-0125-y\n10.1038/s41434-019-0090-7\n10.1080/10715762.2018.1468564\n10.1016/j.jgr.2017.07.009\n10.1016/j.freeradbiomed.2016.11.046\n10.3390/biomedicines9101406\n10.1210/en.2007-0828\n10.1111/jnc.13978\n10.3389/fphar.2022.913124\n10.1007/s11011-020-00634-y\n10.1111/adb.12521\n10.3390/cells10071603\n10.1007/s11356-021-17736-4\n10.31083/j.jin2003076\n10.1016/j.cell.2014.07.051\n10.31487/j.nnb.2021.03.03\n10.1093/schbul/sbl033\n10.1158/1055-9965.EPI-20-1762",
    "journal": "Cells",
    "keywords": [
        "chemo-brain",
        "cognitive impairment",
        "kynurenic acid",
        "redox environment"
    ],
    "methods": null,
    "publication_date": "2024-12-17",
    "pubmed_id": "39682737\n19934210\n16372017\n22408567\n33232037\n30186799\n38098859\n32091339\n29073552\n30956230\n25058905\n12570712\n32069876\n33216283\n36823675\n34884513\n32346964\n27845242\n28828008\n26004930\n26970015\n24647121\n24473062\n34862742\n29977455\n26041992\n21796108\n22678511\n19187269\n11422455\n15836634\n32738461\n25100593\n33498402\n22939820\n32276479\n31035402\n29429900\n38136155\n32768617\n34322665\n28077715\n34356349\n30911969\n34110802\n22312559\n17253547\n26001812\n31308477\n29742938\n31695559\n27908784\n34680523\n17962345\n28178754\n35910350\n33165734\n28557352\n34206739\n34825328\n34645105\n25259918\n35662811\n16920787\n33849970",
    "results": null,
    "title": "Modulation of Brain Kynurenic Acid by N-Acetylcysteine Prevents Cognitive Impairment and Muscular Weakness Induced by Cisplatin in Female Rats.",
    "xml": "<Element 'PubmedArticle' at 0x7885035d4400>"
}