The Cellular Genesis of Metabolic Syndrome and the Role of Anti-urate Drugs in Hyperuricemia Patients: A Systematic Review

Hyperuricemia results due to the underexcretion of uric acid through kidneys or overproduction due to either intake of purine-rich foods, a high caloric diet, or a decreased activity of purine recycler hypoxanthine-guanine phosphoribosyl transferase (HGPRT). Increased xanthine oxidoreductase (XOR) enzyme activity may contribute to hyperuricemia. Literature provides growing evidence that an independent component that contributes to the development of metabolic syndrome (MetS) and associated comorbidities is hyperuricemia. Thus, precise cellular mechanisms involved during MetS and related comorbidities in hyperuricemia, and the role of anti-urate medicines in these mechanisms require further investigations. We searched online libraries PubMed and Google Scholar for data collection. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines for literature identification, selection, screening, and determining eligibility to produce unbiased meaningful outcomes. We applied quality assessment tools for the quality appraisal of the studies. And, outcomes were extracted from the selected studies, which revealed the relationship between hyperuricemia and MetS components by causing inflammation, endothelial dysfunction, oxidative stress, and endoplasmic reticulum stress. The selected studies reflected the role of xanthine oxide (XO) inhibitors beyond inhibition. This systematic review concluded that hyperuricemia independently causes inflammation, oxidative stress, endothelial damage, and endoplasmic reticulum stress in patients with hyperuricemia. These mechanisms provide a cellular basis for metabolic syndrome and related comorbidities. In this context, XO inhibitors and their beneficial effects go beyond XOR inhibition to ameliorate these pathological mechanisms.