However, the effects of MB on key tau kinases have not been explored extensively (131). Recent studies advocate that MB modulates the activity of molecular chaperones in neurons, reduces mitochondrial superoxide production, enhances mitochondrial functions, upregulates Nrf2, and induces autophagy (125â130). The beneficial effects of MB on the cognitive performance of AD patients stem from its ability to inhibit tau aggregation, though the exact mechanism is still under discussion (121â124). Methylene blue (MB), a phenothiazine dye, has been under investigation for treating AD, cancer, malaria, and other human diseases (118â120). Narendran Annadurai, Viswanath Das, in Protein Kinase Inhibitors, 2022 4.3.3 Methylene blue Although more studies are warranted, it may be prudent to reserve MB for rescue therapy, as opposed to using it as a preventive agent. These reports highlight the need for more studies on the safety and possible poor outcomes associated with MB. In another case report, MB was causally linked to the development of methemoglobinemia during CPB. The use of MB has also been implicated in causing serotonin syndrome through its inhibition of monoamine oxidase-A enzyme. In a retrospective analysis of 57 patients with vasoplegia during cardiac surgical procedures and CPB, use of MB as treatment for vasoplegia was independently associated with poor outcomes. MB causes transient discoloration of the urine and the skin and interferes with pulse oximetry measurements of arterial oxygen saturation. At a dose of 3â¯mg/kg given during CPB, MB was shown to increase SVR and MAP without adverse effects in a randomized trial of patients taking angiotensin-converting enzyme inhibitors, as well as decrease pressor requirements and serum lactate levels after CPB. MB has been used as a rescue treatment for profound vasodilatory shock in several settings, including cardiac surgery. MB, a substance commonly used intravenously during surgical procedures for its ability to dye certain tissues, inhibits guanylate cyclase and hence the production of cyclic guanosine monophosphate, which is known to increase vascular smooth muscle relaxation. Kaplan MD, CPE, FACC, in Kaplan's Essentials of Cardiac Anesthesia (Second Edition), 2018 Methylene Blue
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