Almost more than one million cases of cancer are diagnosed annually worldwide, among which colorectal cancer is highly prevalent. Oxaliplatin (OXP) is a third-generation platinum-based antineoplastic agent, used primarily for colorectal cancer, marketed as FOLFOX, a combination drug of oxaliplatin, 5-fluorouracil, and folinic acid. OXP works by binding to the DNA nucleus of the tumor cell, interrupting DNA replication and RNA transcription, and ultimately inhibiting neoplastic growth. Furthermore, it also affects normal cells leading to peripheral neuropathy and therefore clinical use is limited. Approximately 50-90% of patients receiving cumulative doses ⦣500 mg/m₂ experience peripheral neuropathy. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay Oxaliplatin-induced peripheral neuropathy (OIPN) is characterized by acute and chronic symptoms; approximately 90% of patients after the infusion manifest acute symptoms which include transient murosias, dysesthesias triggered or exacerbated by exposure to cold. Conversely, long-term exposure produces sensory and motor dysfunction that could lead to discontinuation of effective therapy. Currently approved remedies for peripheral neuropathy are limited as they only provide symptomatic relief. Chemically OXP is a platinum atom bonded by 1,2-diaminocyclohexane (DACH) and oxalate, which metabolizes to oxalate and dichloro(1,2-diaminocyclohexane)platinum. The exact pathogenetic mechanism underlying OIPN is still unclear, in vitro studies have outlined that acute neurotoxicity is involved in the alteration of Na˖-k˖ channel functioning by blocked oxalate. On the other hand the accumulation of platinum adducts in the DRG via organic cation transporters namely OCT1/2 is due to chronic neurotoxicity, leading to mitochondrial and nuclear DNA damage resulting in neuronal dysfunction, alteration of redox potential, inhibition of neurite growth and mitochondrial dysfunction. Oxidative stress is a major underlying cause of mitochondrial dysfunction, inflammation, and apoptosis that ultimately trigger neurodegeneration. OXP alters the AMPK-mediated PPARϒ pathway and inhibits mitophagy and mitochondrial biogenesis resulting in cell death and thus peripheral neuropathy. It causes deficits in the ETC chain leading to the accumulation of ROS and reduced levels of antioxidants (GSH, SOD, GST, HO-1 etc...) via Nrf2. Therefore, there is a therapeutic need to improve antioxidant levels mediated by Nrf2 and mitochondrial biogenesis and prevent oxidative stress associated with mitochondrial dysfunction. Please note: this is just an example. Get a custom paper from our expert writers now. Customize EssayUmbelliferone (UMB) chemically a 7-hydroxycoumarin, a coumarin derivative of benzopyrone, is found in many familiar plants of the Umbelliferae family such as carrot, coriander, and garden angelica, as well as in plants of other families such as the hawkweed. It is a yellowish-white crystalline solid that has slight solubility in hot water, but high solubility in ethanol. UMB has been reported to exhibit antioxidant, anti-hyperglycemic, antineoplastic, and anti-inflammatory activities. Reports have also shown that it has a promising effect in attenuating the levels of antioxidants, PPARγ and Nrf2. Therefore, this study was undertaken to evaluate the protective effect of UMB on oxaliplatin-induced peripheral neuropathy (OIPN) by mainly targeting Nrf2 and AMPK pathway.