Effect of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility on uric acid metabolism and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in rats with hyperuricemia

Chin J Integr Med. 2017 Jul;23(7):535-542. doi: 10.1007/s11655-016-2649-0. Epub 2017 Jan 24.

Abstract

Objective: To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility (PR) on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in rats with hyperuricemia.

Methods: Seventy male Sprague Dawley (SD) rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses (3.5, 7, 14 g/kg). Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid (SUA), blood urea nitrogen (BUN) and creatinine (Cr) were determined. In addition, the contents of NGAL and KIM-1 in urine and the mRNA and protein expressions of xanthine oxidase (XOD) in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin (HE) stain method.

Results: Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD mRNA and protein in the hyperuricemia rats were increased signifificantly (P<0.01). PR signifificantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the mRNA and protein expressions of hepatic XOD (P<0.05 or P<0.01). In addition, the pathological changes of kidney were signifificantly suppressed by oral administration of PR.

Conclusions: PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.

Keywords: Chinese medicine; Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility; hyperuricemia; kidney injury molecule-1; neutrophil gelatinase-associated lipocalin; xanthine oxidase.

MeSH terms

  • Animals
  • Blood Urea Nitrogen
  • Cell Adhesion Molecules / urine*
  • Creatinine / blood
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Hyperuricemia / blood
  • Hyperuricemia / drug therapy*
  • Hyperuricemia / enzymology
  • Hyperuricemia / urine*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / complications
  • Kidney Diseases / drug therapy
  • Kidney Diseases / pathology
  • Kidney Diseases / urine
  • Lipocalin-2 / urine*
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Uric Acid / blood
  • Uric Acid / metabolism*
  • Xanthine Oxidase / genetics
  • Xanthine Oxidase / metabolism

Substances

  • Cell Adhesion Molecules
  • Drugs, Chinese Herbal
  • Havcr1protein, rat
  • Lipocalin-2
  • RNA, Messenger
  • Uric Acid
  • Creatinine
  • Xanthine Oxidase