RESUMO
Metformin (MTF) is the only biguanide included in the World Health Organization's list of essential medicines; representing a widespread drug in the management of diabetes mellitus. With its accessibility and affordability being one of its biggest assets, it has become the target of interest for many trying to find alternative treatments for varied pathologies. Over time, an increasing body of evidence has shown additional roles of MTF, with unexpected interactions of benefit in other diseases. Metformin (MTF) holds significant promise in mitigating ischemia-reperfusion injury (IRI), particularly in the realm of organ transplantation. As acceptance criteria for organ transplants expand, IRI during the preservation phase remain a major concern within the transplant community, prompting a keen interest in MTF's effects. Emerging evidence suggests that administering MTF during reperfusion may activate the reperfusion injury salvage kinase (RISK) pathway. This pathway is pivotal in alleviating IRI in transplant recipients, potentially leading to improved outcomes such as reduced rates of organ rejection. This review aims to contextualize MTF historically, explore its current uses, pharmacokinetics, and pharmacodynamics, and link these aspects to the pathophysiology of IRI to illuminate its potential future role in transplantation. A comprehensive survey of the current literature highlights MTF's potential to recondition and protect against IRI by attenuating free radical damage, activating AMP-activated protein kinase to preserve cellular energy and promote repair, as well as directly reducing inflammation and enhancing microcirculation.
RESUMO
Background: Cardiovascular and renal diseases represent a major determinant for the morbidity and mortality associated with obesity and type 2 diabetes mellitus (T2DM). Bariatric surgery is considered one of the few treatments with the potential to reverse cardiovascular, renal and metabolic disease. Methods: Prospective study of patients undergoing sleeve gastrectomy collecting pre- and post-surgery creatinine, eGFR, glucose, insulin, total, LDL/HDL cholesterol, triglycerides, parathyroid hormone, vitamin D3, C- Reactive Protein (CRP), blood count, weight, body mass index (BMI), bilateral carotid intima media thickness (IMT), flow-mediated dilation (FMD) and epicardial adipose tissue (EAT). Measurements were compared at 1 year follow up. Results: 24 patients were included in the study. Cardiovascular parameters, as HDL-cholesterol (p = 0.002), IMT (p = 0.003), EAT (p < 0.001) and FMD (p = 0.001) showed significant improvement after surgery. Secondary renal outcomes including Vitamin D3 (p < 0.0001), Calcium (p = 0.006), RBCs (p = 0.007), HCO3- (p = 0.05) also ameliorated as well as BMI (p < 0.001). Conclusions: Sleeve gastrectomy has a positive impact on cardiovascular, renal, and metabolic parameters in patients with morbid obesity, suggesting it may halt the progression of these diseases even in the preclinical stage. Further research is needed to explore the long-term effects underlying these improvements.
RESUMO
Cancer cells are characterized by the reprogramming of certain cell metabolisms via activation of definite pathways and regulation of gene signaling. Ischemia-reperfusion injury (IRI) is characterized by tissue damage and death following a lack of perfusion and oxygenation. It is most commonly seen in the setting of organ transplantation. Interestingly, the microenvironments seen in cancer and ischemic tissues are quite similar, especially due to the hypoxic state that occurs in both. As a consequence, there is genetic signaling involved in response to IRI that has common pathways with cancer. Some of these changes are seen across the board with many cancer cells and are known as Hallmarks of Cancer, among which are aerobic glycolysis and the induction of angiogenesis. This literature review aims to compare the metabolic pathways that are altered in cancer tissues and in normal tissues subjected to IRI in order to find common adaptive processes and to identify key pathways that could represent a therapeutic target in both pathologies. By increasing our understanding of this relationship, clinical correlations can be made and applied practically to improve outcomes of transplanted organs, given the known association with acute rejection, delayed graft function, and poor graft survival. The following metabolic pathways are discussed in our review, both in the setting of cancer and IRI: apoptosis, glycolysis, and angiogenesis. The role of the immune system in both pathologies as well as mitochondrial function and the production of reactive oxygen species (ROS) are reviewed.