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DHODH, a key enzyme in the pyrimidine synthesis pathway, reduces mitochondrial CoQ 10 to CoQ 10 H 2 and collaborating with mitochondrial GPX4 to combat mitochondrial specific lipid peroxidation

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Reduced renal clearance of methotrexate has been associated to increase its half-life and making leucovorin ineffective which may induce the further toxicities such as myelosuppression, mucositis and more pronounced nephrotoxicity.94 Higher plasma concentration of methotrexate significantly decreases the NADPH production and subsequent depletion of GSH that ultimately results into impaired antioxidant defense system and cellular oxidative stress.95 Jahovic et al