Impact of high salt diets on CHOP-mediated apoptosis and renal fibrosis in a rat model.

BACKGROUND: Prolonged and excessive salt intake accelerates oxidative stress in kidney tissues, which brings about ER stress. The PERK/ATF4/CHOP/BCL-2 signaling pathway has an essential role in ER stress-induced apoptosis. The present study aimed to investigate the effect of high salt diets on the development of renal fibrosis through CHOP-mediated apoptosis. METHODS AND RESULTS: Twenty-five male Wistar rats were randomly divided into five groups (n = 5 each). Groups 1-5 were treated with 0%, 0.5%, 1%, 1.2%, 1.5% of NaCl dissolved in distilled water, respectively, for 8 weeks. To detect the degree of renal tubular damage, urinary KIM-1 was measured. The slides of renal tissues were stained via Masson's Trichrome staining methods for fibrosis detection. The relative gene expression of ATF4, CHOP, and BCl-2 in renal tissues were analyzed using the qRT-PCR method. The results revealed no significant difference between the urea, creatinine, and urine flow rate of the rats receiving different concentrations of NaCl (groups 2-5) and those of the control group (group 1). The rats treated with 1.5% NaCl (group 5) showed significant elevations in urinary KIM-1 and the mRNA level of CHOP compared to the control group. Mild renal fibrosis was also observed in group 5. CONCLUSIONS: Excessive salt intake leads to fibrosis as it induces the PERK/ATF4/CHOP/BCL-2 signaling pathway in renal tissues. KIM-1 is detectable in urine before the impairment of renal function which can be used as a diagnostic marker to prevent the development of progressive renal failure.

Effect of Metformin on Circulating Levels of Inflammatory Markers in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Emerging evidence indicates that metformin has anti-inflammatory effect; however, the results differ concerning randomized controlled trails of the effect of metformin on inflammatory markers in type 2 diabetes (T2D) patients. OBJECTIVE: This study reassessed the data on the effect of metformin treatment on inflammatory markers in T2D patients through a systematic review and meta-analysis. METHODS: A systematic search was performed in the PubMed, ISI Web of Science, EMBASE, Cochrane Library and Scopus databases to collect relevant published data up to September 2020. Data of each study was combined using random-effects model. Subgroup analysis was performed based on subgroups of the treatment duration, dose and target population. RESULTS: Thirteen RCTs including 1776 participants with T2D were analyzed. Although CRP levels significantly decreased [SMD: -0.76 mg/L; 95% CI (-1.48, -0.049); P = 0.036] in patients with T2D following metformin treatment, circulating levels of TNF-α [SMD: -0.17 pg/mL; 95% CI (-0.55, 0.20); P = 0.37] and IL-6 [SMD: -0.06 pg/mL; 95% CI (-0.38, 0.25); P = 0.69] were insignificant after metformin treatment. Compared to treatment duration of less than 24 weeks, longer treatment duration (more than 24 weeks) was associated with reduced level of CRP. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Based on available evidence from RCTs in this meta-analysis, metformin decreased CRP level. However, strategies for the treatment of inflammation should focus on metformin in patients with T2D. CONCLUSION: The present study evidences that therapy with metformin can reduce CRP level significantly in T2D patients compared to other inflammatory markers.