These data demonstrate that hepatocyte XOR activity is a critical determinant of systemic UA homeostasis, that deletion of hepatocyte <i>Xdh</i> is sufficient to prevent systemic HyUA of obesity, and that neither prevention nor correction of HyUA improves insulin resistance/dyslipidemia in obesity.
Xanthine oxidase (XO) is a form of xanthine oxidoreductase, a type of enzyme that plays a key role in the induction of hyperuricemia and raising superoxide radical level in blood.
Patients with deficient hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity present hyperuricemia and/or hyperuricosuria, with a variable degree of neurological manifestations.
Partial deficiency of this enzyme can result in the overproduction of uric acid leading to a severe form of gout, whilst a virtual absence of HPRT activity causes the Lesch-Nyhan syndrome which is characterised by hyperuricaemia, mental retardation, choreoathetosis and compulsive self-mutilation.
Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and <i>In Vitro</i> Verification with Cells.
Together with high ABCG2 expression in extra-renal tissues, our data suggest that the 'overproduction type' in the current concept of hyperuricemia be renamed 'renal overload type', which consists of two subtypes-'extra-renal urate underexcretion' and genuine 'urate overproduction'-providing a new concept valuable for the treatment of hyperuricemia and gout.
Moreover, we found the significant decrease in protein expression of URAT1 and GLUT9, and the significant increase in protein expression of OAT1 in the kidney in AFPR treated groups compared to the model groups of hyperuricemia.
Plasma membrane expression of breast cancer resistance protein (BCRP), a uric acid efflux transporter, was decreased under hyperuricemia, though the total cellular expression of BCRP remained constant.
Erythrocyte assays for hypoxanthine guanine phosphoribosyltransferase (HGPRT) activity performed on two male half-siblings with hyperuricemia, produced results consistent with classic Lesch-Nyhan syndrome.
Moreover, we found the significant decrease in protein expression of URAT1 and GLUT9, and the significant increase in protein expression of OAT1 in the kidney in AFPR treated groups compared to the model groups of hyperuricemia.
Collectively, our results suggest that THP deficiency can cause progressive disturbances in renal functions via initially NKCC2 dysfunction and later compensatory responses, resulting in prolonged activation of the renin-angiotensin-aldosterone axis and hyperuricemia.
We observed that the two flavones possess potent effect in hyperuricemia mice by decreasing the level of mURAT1 and inhibiting XO activity, which contribute to enhancing uric acid (UA) excretion and improving hyperuricemia-induced renal dysfunction.
G. pensylvanicum extract showed activity in reducing serum uric acid (Sur) through effect renal glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1) and urate transporter 1 (URAT1) mainly and inhibited XO activity in vivo of mice with PO induced hyperuricemia.
CAGM and its modified formulation significantly ameliorated PO-induced hyperuricemia in mice, which might be partially attributable to reductions of hepatic XOD and renal URAT1 levels.
The expression of URAT1 was returned to normal, resulting in an increase of renal urate excretion and consequent healing of adenine-induced hyperuricemia in mice.
About 90% of patients develop hyperuricemia due to insufficient urate excretion; thus, it is important to develop URAT1 inhibitors that could enhance renal urate excretion by blocking the reabsorption of urate anion.
Collectively, our results suggest that THP deficiency can cause progressive disturbances in renal functions via initially NKCC2 dysfunction and later compensatory responses, resulting in prolonged activation of the renin-angiotensin-aldosterone axis and hyperuricemia.