Folic acid attenuates hyperhomocysteinemia-induced glomerular damage in rats.

Abstract

The present study investigated whether lowering plasma homocysteine (Hcy) with folic acid (FA) could attenuate hyperhomocysteinemia (HHcy)-associated glomerular damage and possible mechanisms. The HHcy animal model was established by intragastric administration with l-methionine in rats. FA was also given intragastrically. Plasma Hcy and creatinine and urinary albumin were measured. Histological and ultrastructural changes were observed by light and electron microscopes. The expression of alpha-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA) and transforming growth factor-beta1 (TGF-β1) in the kidney was examined by immunohistochemical staining and western blot analysis. The administration of l-methionine induced HHcy in rats. The HHcy rats developed glomerulosclerosis and fibrosis. Plasma creatinine concentration and urinary albumin excretion were also significantly increased in HHcy rats. Effacement and extensively fusion of podocyte foot process was observed in HHcy rats, which was associated with decreased expression of nephrin protein in renal cortex of HHcy rats. Supplementation with FA lowered plasma Hcy significantly. Plasma creatinine concentration and urinary albumin excretion were also significantly attenuated by FA. Morphologically, HHcy-associated glomerulosclerosis, fibrosis, podocyte foot process effacement and loss of podocyte nephrin, were significantly improved by FA. The expressions of α-SMA, PCNA and TGF-β1 were increased in renal cortex of HHcy rats, and which were also partially reversed by FA. These data suggest that elevated plasma Hcy is an important pathogenic factor for glomerular damage. Lowering plasma Hcy by FA can inhibit TGF-β1 expression and attenuate HHcy-induced glomerular damage.

• Authors: Lu Cao, Xiaoying Lou, Zhaoxia Zou, Nana Mou, Weikang Wu, Xiongqing Huang, Hongmei Tan
• Journal: Microvascular research (Microvasc Res) Vol. 89 Pg. 146-52 (Sep 2013) ISSN: 1095-9319 [Electronic] United States
• PMID: 23859838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Transforming Growth Factor beta1
• Homocysteine
• Collagen
• Folic Acid
• Creatinine

Topics

• Albuminuria (metabolism)
• Animals
• Cell Proliferation
• Collagen (chemistry)
• Creatinine (metabolism)
• Folic Acid (pharmacology)
• Gene Expression Regulation
• Homocysteine (metabolism)
• Hyperhomocysteinemia (drug therapy, metabolism)
• Immunohistochemistry
• Kidney (drug effects)
• Kidney Cortex (metabolism)
• Kidney Diseases (metabolism, pathology)
• Kidney Glomerulus (metabolism)
• Podocytes (cytology)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Transforming Growth Factor beta1 (metabolism)
• Up-Regulation