Administration of Procyanidins from Grape Seeds Reduces Serum Uric Acid Levels and Decreases Hepatic Xanthine Dehydrogenase/Oxidase Activities in Oxonate‐Treated Mice

Abstract

In this study we have investigated the effects of administration of procyanidins from grape seeds on serum uric acid levels in a model of hyperuricaemia in mice pretreated with oxonate, as well as the xanthine dehydrogenase and xanthine oxidase activities in mouse liver in vivo. The procyanidins, when orally administered to the oxonate-pretreated hyperuricaemic mice, were able to elicit a dose-dependent hypouricaemic effect. At a dose of 400 mg/kg for 3 days, the serum urate levels of the oxonate-pretreated mice were not different from the normal mice. In addition, the hepatic activities of xanthine dehydrogenase and xanthine oxidase in the procyanidins-treated mice were found to decrease significantly. However, the hypouricaemic effects observed in the experimental animals did not seem to parallel the changes in xanthine dehydrogenase and xanthine oxidase activities, implying that the procyanidins might be acting via other mechanisms apart from simple inhibition of enzyme activities. Furthermore, the procyanidin-treated animals exhibited normal growth while the allopurinol-treated animals exhibited some retarded growth. These results demonstrated for the first time that the procyanidins from grape seeds possess in vivo urate-lowering activities. The potential application of these natural compounds in the treatment of hyperuricaemia is discussed.Gout is a common metabolic disorder in human, reportedly afflicting more than 2 million men and women in the United States alone (Kramer & Curhan 2002). The disease is also rising rapidly in China (Li et al. 1997) due probably to recent changes in dietary habits. Gout is often associated with elevated serum levels of uric acids, resulting in the deposition of urate crystals in the joints and kidneys, causing inflammation as well as gouty arthritis and uric acid nephrolithiasis (Kramer & Curhan 2002). Thus, the treatment of gout entails the use of non-steroidal antiinflammatory drugs (NSAIDs) for symptomatic relief as well as xanthine oxidase inhibitor (Liote 2003) to curtail the endogenous production of uric acid. However, NSAIDs produce characteristic side effects, especially in patients with preexisting renal insufficiency, peptic ulceration, and gastric problems (Taylor et al. 2001;Wardi & Shirin 2003). Allopurinol is the most common clinically used xanthine oxidase inhibitor prescribed for the treatment of gout. However its use is sometimes limited by hypersensitivity problems , and even fatal liver necrosis (Pereira et al. 1998).To circumvent such problems of allopurinol and to look for possible alternatives, attempts have been made to identify compounds with xanthine oxidase inhibitory activities Author for correspondence: Ling Dong Kong, School of Life Sciences, Nanjing University, Nanjing 210093, China (fax π86 25 83594691, e-mail kongld/nju.edu.cn). from natural sources (Kong et al. 2000;Zhou et al. 2001). In the present study we report that administration of procyanidins from grape seeds to oxonate-pretreated hyperuricaemic mice results in the reducti...

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Cerebral Oxidative Stress and Mitochondrial Dysfunction in Oxonate-Induced Hyperuricemic Mice

“…These administrations were based on the previous papers. 12,13) The mice were sacrificed 3 hr after the administration. Cerebrum was immediately excised after decapitation, and then weighed, washed with saline and homogenized in ice-cold 0.01 M phosphate buffered saline (PBS) (pH 7.4).…”

Inhibition of 3,5,2′,4′-Tetrahydroxychalcone on Production of Uric Acid in Hypoxanthine-Induced Hyperuricemic Mice

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