No abstract

Hyperuricemia often accompanies hypertension, diabetes, dyslipidemia, metabolic syndrome, and chronic renal disease; it is also closely related to cardiovascular disease. Moreover, several epidemiological studies have linked hyperuricemia and ischemic stroke. However, uric acid may also have neuroprotective effects because of its antioxidant properties. An association between low uric acid levels and neurodegenerative diseases has been suggested, which may be attributed to diminished neuroprotective effects as a result of reduced uric acid. This review will focus on the relationship between uric acid and various neurological diseases including stroke, neuroimmune diseases, and neurodegenerative diseases. When considering both the risk and pathogenesis of neurological diseases, it is important to consider the conflicting dual nature of uric acid as both a vascular risk factor and a neuroprotective factor. This dual nature of uric acid is important because it may help to elucidate the biological role of uric acid in various neurological diseases and provide new insights into the etiology and treatment of these diseases.

The importance of uric acid, the final metabolite of purines excreted by the kidneys and intestines, was not previously recognized, except for its role in forming crystals in the joints and causing gout. However, recent evidence implies that uric acid is not a biologically inactive substance and may exert a wide range of effects, including antioxidant, neurostimulatory, proinflammatory, and innate immune activities. Notably, uric acid has two contradictory properties: antioxidant and oxidative ones. In this review, we present the concept of “dysuricemia,” a condition in which deviation from the appropriate range of uric acid in the living body results in disease. This concept encompasses both hyperuricemia and hypouricemia. This review draws comparisons between the biologically biphasic positive and negative effects of uric acid and discusses the impact of such effects on various diseases.

Persistent high serum triglyceride (TG) and free fatty acid (FFA) levels, which are common in metabolic syndrome and type 2 diabetes, are risk factors for cardiovascular events because of exacerbated hemorheology. To explore the effects of pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, on hemorheology, we performed a single-center, nonrandomized, controlled study in patients with type 2 diabetes (HbA1c 6–10%) or metabolic syndrome, with fasting TG levels of ≥ 150 mg/dL and a whole blood transit time of > 45 s on a microarray channel flow analyzer (MCFAN). Patients were divided into a study group, receiving 0.2 mg/day of pemafibrate (n = 50) for 16 weeks, and a non-pemafibrate control group (n = 46). Blood samples were drawn 8 and 16 weeks after entry to the study to evaluate whole blood transit time as a hemorheological parameter, leukocyte activity by MCFAN, and serum FFA levels. No serious adverse events were observed in either of the groups. After 16 weeks, the pemafibrate group showed a 38.6% reduction in triglycerides and a 50.7% reduction in remnant lipoproteins. Pemafibrate treatment did not significantly improve whole blood rheology or leukocyte activity in patients with type 2 diabetes mellitus or metabolic syndrome complicated by hypertriglyceridemia and exacerbated hemorheology.