Nearly one million cases of cancer are diagnosed each year worldwide, among which colorectal cancer is very common. Oxaliplatin (OXP) is a third-generation platinum-based antineoplastic agent mainly used for colorectal cancer, marketed as FOLFOX, a combination drug of oxaliplatin, 5-fluorouracil and folinic acid. OXP works by binding to the DNA core of cancer cells, interrupting DNA replication and RNA transcription and ultimately inhibiting neoplastic malignancy. Additionally, it also affects normal cells, leading to peripheral neuropathy, which limits its clinical use. Approximately 50 to 90% of patients receiving cumulative doses ⦣ 500 mg/m₂ suffer from peripheral neuropathy. Say no to plagiarism. Get a tailor-made essay on “Why Violent Video Games Should Not Be Banned”? Get the original essay Oxaliplatin-induced peripheral neuropathy (OIPN) is characterized by acute and chronic symptoms; approximately 90% of patients after infusion experience acute symptoms, including transient parathesia, dysthesia triggered or exacerbated by exposure to cold. In contrast, long-term exposure produces sensory and motor dysfunction that could ultimately lead to discontinuation of effective treatment. Currently approved remedies for peripheral neuropathy are limited because they only provide symptomatic relief. Chemically, OXP is a platinum atom bonded to 1,2-diaminocyclohexane (DACH) and oxalate, which metabolizes to oxalate and dichloro(1,2-diaminocyclohexane)platinum. The exact pathological mechanism underlying OIPN is not yet clear, in vitro studies have shown that acute neurotoxicity is involved in the impairment of Na˖-k˖ channel function 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, which results in damage to mitochondrial DNA as well as nuclear DNA, thus leading to neuronal dysfunction, alteration of redox potential, inhibition of neurite growth. and mitochondrial dysfunction. Oxidative stress is one of the major underlying causes of mitochondrial dysfunction, inflammation, and apoptosis that ultimately trigger neurodegeneration. OXP modifies the AMPK-mediated PPARϒ pathway and inhibits mitophagy and mitochondrial biogenesis, ultimately leading to cell death and thus peripheral neuropathy. It causes deficits in the ETC chain leading to the accumulation of ROS and a decrease in antioxidant levels (GSH, SOD, GST, HO-1 etc...) via Nrf2. Therefore, there is a therapeutic need to improve Nrf2-mediated antioxidant levels and mitochondrial biogenesis and prevent oxidative stress associated with mitochondrial dysfunction. Keep in mind: this is just a sample. Get a personalized article from our expert writers now. Get a Custom Article EssayUmbelliferone (UMB) chemically a 7-hydroxycoumarin, a coumarin derivative of benzopyrone, is present in many familiar plants of the Umbelliferae family such as carrot, coriander, and garden angelica, as well than in plants from other families such as mouse-eared 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 he has..