Nutr Res Pract.  2021 Feb;15(1):26-37. 10.4162/nrp.2021.15.1.26.

Effects of resveratrol on the inflammatory response and renal injury in hyperuricemic rats

• Xiao B
• Ma W
• Zheng Y
• Li Z
• Li D
• Zhang Y
• Li Y
• Wang D

• KMID: 2511671
• DOI: http://doi.org/10.4162/nrp.2021.15.1.26

Abstract

BACKGROUND/OBJECTIVES
Hyperuricemic nephropathy is a common cause of acute kidney injury. Resveratrol can ameliorate kidney injury, but the explicit mechanism remains unclear. We investigated the effects of resveratrol on the inflammatory response and renal injury in hyperuricemic rats.
MATERIALS/METHODS
A rat model of hyperuricemic nephropathy was established by the oral administration of a mixture of adenine and potassium oxinate. Biochemical analysis and hematoxylin and eosin staining were performed to assess the rat kidney function. Enzymelinked immunosorbent assays were performed to evaluate the immune and oxidative responses.
RESULTS
The expression levels of urine albumin and β2-microglobulin were significantly decreased after resveratrol treatment. In addition, the levels of serum creatinine and uric acid were significantly decreased in the resveratrol groups, compared with the control group.The levels of proinflammatory factors, such as interleukin-1β and tumor necrosis factor-α, in kidney tissue and serum were also increased in the hyperuricemic rats, and resveratrol treatment inhibited their expression. Moreover, the total antioxidant capacity in kidney tissue as well as the superoxide dismutase and xanthine oxidase levels in serum were all decreased by resveratrol treatment.
CONCLUSIONS
Resveratrol may protect against hyperuricemic nephropathy through regulating the inflammatory response.

Keyword

Hyperuricemia; resveratrol; kidney diseases; inflammation; anti-oxidative effect

Figure

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  Fig. 1 The serum uric acid level in the hyperuricemia group after treatment with different dosages of resveratrol. (A) Adenine (100 mg/kg/day) and potassium oxinate (1,000 mg/kg/day) or vehicle were orally administered every morning. Low-dose (25 mg/kg/day), medium-dose (50 mg/kg/day), and high-dose (100 mg/kg/day) RES were administered every afternoon. (B) The serum levels of uric acid from the control or hyperuricemic rats treated without or with different concentrations of RES were measured. Samples were collected at 7, 14, and 21 days after treatment. Data are expressed as the mean ± SEM (n = 8).RES, resveratrol; SEM, standard error of the mean; BUN, blood urea nitrogen.*P < 0.05, **P < 0.01 compared with the hyperuricemia group.

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  Fig. 2 The body weight and kidney indices of the hyperuricemic rats were measured after treatment with resveratrol. (A) The body weight and (B) kidney indices of the control or hyperuricemic rats treated without or with different concentrations of RES were measured at 0, 7, 14, and 21 days after treatment. Data are presented as the mean ± SEM (n = 8).RES, resveratrol; SEM, standard error of the mean.**P < 0.01 compared with the hyperuricemia group.

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  Fig. 3 The different doses of RES were administered every afternoon. (A) Serum urea nitrogen and (B) creatinine were measured to assess the renal function. Data are presented as the mean ± SEM (n = 8).RES, resveratrol; SEM, standard error of the mean.*P < 0.05, **P < 0.01 compared with the hyperuricemia group.

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  Fig. 4 The levels of (A) urine protein contents, (B) microalbumin, and (C) β2-microglobulin in urine from the control or hyperuricemic rats treated without or with different concentrations of RES were measured. Data are presented as the mean ± SEM (n = 8).RES, resveratrol; SEM, standard error of the mean.*P < 0.05, **P < 0.01 compared with the hyperuricemia group.

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  Fig. 5 RES ameliorates renal morphological changes and reduces the infiltration of inflammatory cells in the kidney. Representative photographs of H&E-stained rat renal sections at a magnification of 200×. The groups were as follows: control group, hyperuricemia group (sham), hyperuricemia with low-dose RES, hyperuricemia with medium-dose RES, and hyperuricemia with high-dose RES. The blue arrows represent eosinophilic insoluble proteins; the black arrow represents salt crystals; and the green arrow represents edema of renal tubular epithelial cells.RES, resveratrol; H&E, hematoxylin and eosin.

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  Fig. 6 RES preserves rat renal function and reduces cytokine production induced by hyperuricemia. The concentrations of (A) MDA, (B) SOD, (C) TAOC, (D) IL-1β, (E) IL-6, and (F) TNF-α in kidney tissue were measured by ELISA. The groups were as follows: control group, hyperuricemia group, hyperuricemia with low-dose RES, hyperuricemia with medium-dose RES, and hyperuricemia with high-dose RES. Data are presented as the mean ± SEM (n = 8).MDA, malondialdehyde; SOD, superoxide dismutase; TAOC, total antioxidant capacity; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α; ELISA, enzyme-linked immunosorbent assay; RES, resveratrol.*P < 0.05, **P < 0.01 compared with the hyperuricemia group.

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  Fig. 7 The levels of (A) SOD, (B) TAOC, (C) XOD, (D) IL-1β, (E) IL-6, and (F) TNF-α in serum were measured by ELISA. The groups were as follows: control group, hyperuricemia group, hyperuricemia with low-dose RES, hyperuricemia with medium-dose RES, and hyperuricemia with high-dose RES. Data are presented as the mean ± SEM (n = 8).SOD, superoxide dismutase; TAOC, total antioxidant capacity; XOD, xanthine oxidase; IL, interleukin; TNF, tumor necrosis factor; ELISA, enzyme-linked immunosorbent assay; RES, resveratrol.*P < 0.05, **P < 0.01 compared with the hyperuricemia group.

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