Production Inhibition and Excretion Promotion of Urate by Fucoidan from Laminaria japonica in Adenine-Induced Hyperuricemic Mice

• Published in: Marine drugs 2018-11, Vol.16 (12), p.472
• Main Authors: Zhang, Dayan, Liu, Huazhong, Luo, Ping, Li, Yanqun
• Format: Article
• Language: English
• Subjects: Adenine; Adenine - toxicity; Adenosine; Adenosine deaminase; Allopurinol; Alternations; Animals; Blood Urea Nitrogen; Catalase; Chemical compounds; Creatinine; Creatinine - blood; Creatinine - urine; Diabetes; Disease; Disease Models, Animal; Drug dosages; Drug Evaluation, Preclinical; Enzymes; Excretion; Fucoidan; hepatorenal functions; Humans; Hypertension; Hyperuricemia; Hyperuricemia - chemically induced; Hyperuricemia - drug therapy; Hyperuricemia - urine; Kidney - metabolism; Kidneys; Laminaria - chemistry; Laminaria japonica; Liver; Liver - drug effects; Liver - metabolism; Male; Malondialdehyde; Metabolism; Mice; Natural products; NF-κB protein; Nitrogen; Pharmacology; Polysaccharides - isolation & purification; Polysaccharides - pharmacology; Polysaccharides - therapeutic use; Reabsorption; Renal Elimination - drug effects; Renal function; Serum; Superoxide dismutase; Transaminase; Transaminases; Treatment Outcome; urate; Urea; Uric acid; Uric Acid - blood; Uric Acid - metabolism; Uric Acid - urine; Xanthine oxidase
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md16120472

This work aims to explore the amelioration of fucoidan on adenine-induced hyperuricemia and hepatorental damage. Adenine-induced hyperuricemic mice were administered with fucoidan, allopurinol and vehicle control respectively to compare the effects of the drugs. Serum uric acid, urea nitrogen, hepatorenal functions, activities of hepatic adenosine deaminase (ADA), xanthine oxidase (XOD), renal urate transporter 1 (URAT1) and NF-κB p65 were assessed. As the serum uric acid, urea nitrogen, creatinine, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) data demonstrated, the adenine not only mediated hepatorenal function disorders, but also induced hyperuricemia in mice. Meanwhile, activities of hepatic ADA and XOD were markedly augmented by adenine, and the expression of URAT1 was promoted, which was conducive to the reabsorption of urate. However, exposure to fucoidan completely reversed those adenine-induced negative alternations in mice, and the activities of hepatic ADA and XOD were recovered to the normal level. It was obvious that hepatic and renal functions were protected by fucoidan treatment. 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. Expression and activation of NF-κB p65 was promoted in kidneys of adenine treated mice, but suppressed in kidneys of mice exposed to fucoidan from or allopurinol. In conclusion, the fucoidan is a potential therapeutic agent for the treatment of hyperuricemia through dual regulatory roles on inhibition of hepatic metabolism and promotion of renal excretion of urate.