Resveratrol Plays Protective Roles on Kidney of Uremic Rats via Activating HSP70 Expression

Abstract

Objective. To investigate the protective effects of resveratrol on kidney of uremic rats and to explore whether the mechanism is associated with heat shock protein 70 (HSP70) expression. Methods. Sixty male Sprague Dawley rats were randomly separated into 5 groups, including sham group, uremic model group, and different doses of resveratrol group (5 mg/kg, 10 mg/kg, and 20 mg/kg). The serum creatinine (Cr) and urea nitrogen (BUN) levels were detected by Automatic Biochemical Analyzer (ABA). The pathological changes of renal tissues and the renal interstitial fibrosis were analyzed by hematoxylin-eosin (HE) and Masson, respectively. The expression of HSP70 protein in renal tissues was detected by immunohistochemistry. The expression of HSP70 and NF-κB pathway-related proteins were detected by Western blot. To further validate the protective role of resveratrol through activating HSP70 in uremic rats, HSP70 activator (17-AAG) and HSP70 inhibitor group (MKT-077) were used. Results. In the model group, the levels of Cr and BUN in serum were significantly increased, and the renal interstitial collagen deposition was also obviously increased (p<0.05). Compared with the model group, the levels of Cr and BUN in different doses of resveratrol groups were remarkably declined, and the renal interstitial collagen deposition was declined (p<0.05). Resveratrol also significantly improved the renal tissue lesions when compared with the model group. In renal tissues, different doses of resveratrol treatment remarkably raised HSP70 and p-IκBα expression and also remarkably declined the level of p-P65 protein (p<0.05). Meanwhile, the effect of 17-AAG was similar to 20 mg/kg resveratrol on NF-κB pathway-related proteins expression. After the added MKT-077 in the resveratrol treatment group, the levels of HSP70 and p-IκBα in the renal tissue were remarkably declined; however, the levels of p-P65 protein was remarkably raised (p<0.05). Conclusion. Resveratrol played a protective role on the kidney of uremic rats through activating HSP70 expression.

Resveratrol: Latest Scientific Evidences of its Chemical, Biological Activities and Therapeutic Potentials

“…Following the addition of MKT-077 (a cationic rhodacyanine dye analogue used for preclinical cancer trials due to its selective toxic effects on cancer cells) there were remarkable reduction in HSP70 and p-IκBα levels in renal tissues of resveratrol-treated group with increased levels of p-P65 protein. 73 Overall, the findings indicate that resveratrol play a positive role in the kidney of uremic rats by activating HSP70 expression. 73 In a study conducted on female Sprague Dawley rats 95 , there was increased total antioxidant status, decreased Cr, BUN, OS-index and total oxidant status as well as reduced weight gain following resveratrol treatment for 15 days.…”

“…Additionally, there was improved renal tissue lesions in resveratrol-treated group as compared to other groups. 73 There was also an increase in HSP70 and p-IκBα expression and decrease in p-65 protein level in renal tissues, for all administered resveratrol doses. Following the addition of MKT-077 (a cationic rhodacyanine dye analogue used for preclinical cancer trials due to its selective toxic effects on cancer cells) there were remarkable reduction in HSP70 and p-IκBα levels in renal tissues of resveratrol-treated group with increased levels of p-P65 protein.…”

“…71 A molecule that is one of the crucial elements in maintaining stable cerebral blood flow or brain-derived neurotrophic factor (BNDF), is known for its neuroprotective effects in many neurodegenerative disorders. Oral resveratrol may exert similar expression as BNDF mRNA in the hippocampus of male Sprague-Dawley rats 73 pre-treated with either resveratrol (10 mg/kg administered orally for four weeks) or a placebo. Resveratrol pre-treated group had a significant surge in BDNF concentration after four weeks indicating that it has some neuroprotective effects.…”

“…A study confirmed the protective effects of resveratrol in uremic rat kidney by investigating the expression of heat shock protein 70 (HSP70). 73 Sprague Dawley rats were classified into five different groups which were sham, uremic and resveratrol (5, 10 and 20 mg/ kg). Serum creatinine (Cr) and blood urea nitrogen (BUN) levels as well as renal interstitial collagen deposition were significantly increased in all groups.…”

A Novel Standardized Method of Renal Biopsy in Mice

“…For example, 5 of 40 glomeruli were +, 5 glomeruli were +++, and the other 30 glomeruli were normal; the GSI can be calculated as follows: GSI = [(1 × 5/40) + (3 × 5/40)] × 100 = 50. The criteria for tubular injury and renal interstitial fibrosis were from the literature [11,12]. The degree of renal tubular injury and renal interstitial fibrosis is expressed as the proportion of damaged renal tubules and the proportion of renal interstitial tissue and fibrosis, respectively.…”