Cardiovascular-related complications (CVCs) are the primary cause of death in patients undergoing hemodialysis (HD), accounting for greater than half of all deaths. Beyond traditional risk factors, chronic inflammation, extreme oxidative stress (OS), and endothelial dysfunction emerge as major contributors to accelerated CVCs in HD patients. Ample evidence shows that HD patients are constantly exposed to excessive OS, due to uremic toxins and pro-oxidant molecules that overwhelm the defense antioxidant mechanisms. The present study highlights the efficiency of natural antioxidant supplementation in managing HD-induced inflammation, OS, and consequently CVCs. Moreover, it discusses the underlying molecular mechanisms by which these antioxidants can decrease mitochondrial and endothelial dysfunction and ameliorate CVCs in HD patients. Given the complex nature of OS and its molecular pathways, the utilization of specific antioxidants as a polypharmacotherapy may be necessary for targeting each dysregulated signaling pathway and reducing the burden of CVCs.

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