{"title":"Different doses of hydroxychloroquine regulate the structure of intestinal flora and glycosyltransferase activity in rats with IgA nephropathy","authors":"Lingling Bao, Xueyan Bian, Liling Ren, Sizeng Bao, Aiwei Zhang","doi":"10.1016/j.imbio.2025.152891","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Hydroxychloroquine (HCQ), by virtue of its ability to reduce proteinuria, is an alternative therapy for Immunoglobulin A nephropathy (IgAN). This study investigated the effects of different doses of HCQ on the structure of intestinal flora and glycosyltransferase activity in IgAN rats.</div></div><div><h3>Methods</h3><div>IgAN model rats constructed by treatment of bovine serum albumin, castor oil and lipopolysaccharide were administered with HCQ (18 or 36 mg/kg) by gavage. Then the number of urine erythrocyte and the renal function of rats were evaluated. The levels of galactose-deficient IgA1 (Gd-IgA1), B cell activation factor (BAFF) and C-reactive protein (CRP) in serum and those of inflammatory factors in renal tissue were detected by ELISA. Renal tissue injury and IgA deposition were assessed by histological analysis. The expressions of Core 1 beta1,3-galactosyltransferase (C1GALT1), Core 1 synthase specific molecular chaperone (COSMC) and ST6 <em>N</em>-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2) were quantified by qRT-PCR, Western blot or in vitro enzyme assays. 16 s rDNA sequencing was used to analyze the structure of intestinal flora in rats.</div></div><div><h3>Results</h3><div>HCQ dose-dependently decreased the levels of serum creatinine, UREA, Gd-IgA1, BAFF, CRP and urine protein, waned the number of urine erythrocyte, inhibited the expressions of inflammatory factors and IgA deposition in renal tissue, and up-regulated the expressions of C1GALT1, COSMC and down-regulated ST6GALNAC2 expression in peripheral blood mononuclear cells (PBMCs).</div></div><div><h3>Conclusion</h3><div>HCQ could reduce glomerular swelling in mesangial area and improve the imbalance of intestinal flora in IgAN rats.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 3","pages":"Article 152891"},"PeriodicalIF":2.5000,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunobiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0171298525000257","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Hydroxychloroquine (HCQ), by virtue of its ability to reduce proteinuria, is an alternative therapy for Immunoglobulin A nephropathy (IgAN). This study investigated the effects of different doses of HCQ on the structure of intestinal flora and glycosyltransferase activity in IgAN rats.
Methods
IgAN model rats constructed by treatment of bovine serum albumin, castor oil and lipopolysaccharide were administered with HCQ (18 or 36 mg/kg) by gavage. Then the number of urine erythrocyte and the renal function of rats were evaluated. The levels of galactose-deficient IgA1 (Gd-IgA1), B cell activation factor (BAFF) and C-reactive protein (CRP) in serum and those of inflammatory factors in renal tissue were detected by ELISA. Renal tissue injury and IgA deposition were assessed by histological analysis. The expressions of Core 1 beta1,3-galactosyltransferase (C1GALT1), Core 1 synthase specific molecular chaperone (COSMC) and ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GALNAC2) were quantified by qRT-PCR, Western blot or in vitro enzyme assays. 16 s rDNA sequencing was used to analyze the structure of intestinal flora in rats.
Results
HCQ dose-dependently decreased the levels of serum creatinine, UREA, Gd-IgA1, BAFF, CRP and urine protein, waned the number of urine erythrocyte, inhibited the expressions of inflammatory factors and IgA deposition in renal tissue, and up-regulated the expressions of C1GALT1, COSMC and down-regulated ST6GALNAC2 expression in peripheral blood mononuclear cells (PBMCs).
Conclusion
HCQ could reduce glomerular swelling in mesangial area and improve the imbalance of intestinal flora in IgAN rats.
期刊介绍:
Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including
• Innate Immunity,
• Adaptive Immunity,
• Complement Biology,
• Macrophage and Dendritic Cell Biology,
• Parasite Immunology,
• Tumour Immunology,
• Clinical Immunology,
• Immunogenetics,
• Immunotherapy and
• Immunopathology of infectious, allergic and autoimmune disease.