Abstract
Membranous nephropathy (MN, also known as membranous glomerulopathy) is one of the many glomerular diseases causing nephrotic syndrome. The literature indicates that autophagy is associated with the homeostasis of podocytes in glomeruli. Curcumin, the main active component in turmeric, has drawn attention for its effective bioactivities against chronic kidney disease. The current study was aimed at assessing the effects of curcumin and exploring the underlying mechanism that mediates autophagy in an animal model of passive Heymann nephritis (PHN) in rats. Passive Heymann nephritis (PHN) was induced in male SD rats by intraperitoneal injection of anti-Fx1A serum. The rats were divided into 3 groups: control (n = 10, normal diet), model group (n = 10, 0.5% sodium carboxymethylcellulose), and curcumin (n = 10, 300 mg/kg/d). The kidney function and oxidative stress indicators were measured using commercial diagnostic kits, and the histomorphology of renal tissues was observed. The number of podocytes was measured by immunohistochemistry. Meanwhile, the autophagosomes in podocyte were analyzed by transmission electron microscopy and the immunofluorescence assay pointing to p62, an autophagic marker. Western blot analyzed the levels of apoptosis, autophagy, PI3K/AKT/mTOR, and Nrf2/HO-1 pathway-associated proteins. The total cholesterol (TC), triglycerides (TG), creatinine (Scr), blood urea nitrogen (BUN), urine volume, and urine albumin of PHN rats were significantly reduced by the administration of curcumin and attenuated renal histomorphological changes in model rats. Meanwhile, curcumin improved the oxidative stress response by decreasing MDA and increasing SOD, GSH, and CAT levels in the kidney of PHN rats. Furthermore, curcumin significantly ameliorated the podocyte loss, along with the fusion, and increased the autophagic vacuoles compared to the PHN control rats. In addition, curcumin downregulated the expression of Bax, Caspase-3, p62, PI3K, p-AKT, and p-mTOR proteins and upregulated the Bcl-2, beclin1, LC3, Nrf2, and HO-1 levels in this animal model. The results provide a scientific basis that curcumin could significantly alleviate the development of MN by inducing autophagy and alleviating renal oxidative stress through the PI3K/AKT/mTOR and Nrf2/HO-1 pathways.
Highlights
Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults worldwide, known as membranous glomerulopathy [1]
Compared with the model group, the ALB and total protein (TP) in the curcumin group were higher than that in the model, and total cholesterol (TC), TG, SCr, blood urea nitrogen (BUN), urine volume, and urine albumin were significantly decreased with curcumin treatment
We investigated the effects of curcumin in the passive Heymann nephritis (PHN) rat model
Summary
Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults worldwide, known as membranous glomerulopathy [1]. It is a glomerular disease, and characteristic changes include proteinuria, the granular deposit of subepithelial immune complexes in the kidney, and diffuse thickening of the glomerular basement membrane (GBM) [2, 3]. MN can be subdivided into idiopathic membranous nephropathy (IMN), originally known as primary MN and secondary MN. Approximately 75% of cases are IMN, which is mainly associated with the antiphospholipase A2 receptor (anti-PLA2R) antibody and thrombospondin type 1 domain-containing 7A (THSD7A) [4, 5], as well as the secondary causes, including infection, autoimmune disease, malignancies, and drugs [3, 6]. There are about 13.28% of primary glomerular diseases in China, mostly concentrated in the elderly with an average of 13% annual growth rate [7], becoming the main type of nephropathy in China.
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