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l ‐Citrulline protects from kidney damage in STZ‐diabetic rodents (151.10)
Author(s) -
RomeroLucas Maritza,
Yao Lin,
Lucas Rudolf,
Caldwell Robert,
Bagi Zsolt
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.151.10
Subject(s) - medicine , endocrinology , diabetic nephropathy , streptozotocin , diabetes mellitus , renal function , kidney disease , nephropathy , kidney , nephron , excretion , chemistry
Rationale. Diabetic nephropathy (DN) is a major cause of end‐stage renal disease. Hypercatabolic states are a common feature of chronic diseases such as diabetes mellitus (DM), and are accompanied by an increase of circulating inflammatory cytokines. Therefore, amino acid supplementation may be effective in counteracting the metabolic consequences of DM, including DN. Aims. To investigate whether L‐citrulline (L‐cit) supplementation represents a safe intervention in DN, and to assess the effects of L‐cit on the inflammatory profile observed in DM. Methods. STZ‐C57BL6 mice and rats received L‐cit or vehicle supplemented in the drinking water (50 mg/kg/day). Human glomerular endothelial cells (HGEC) were exposed to high glucose (HG, 25 mM)‐supplemented medium. Results. L‐cit supplementation markedly reduced urinary albumin excretion (µg/day, C=141.4 ± 23.8; STZ= 807.2 ± 205.1 p<0.001 vs C; L‐cit‐STZ= 193.4 ± 109.8 p<0.05 vs STZ), tubulo‐interstitial collagen deposition, and kidney hypertrophy observed in untreated STZ‐mice and rats. These effects were accompanied by enhanced plasma levels of the anti‐inflammatory cytokine IL‐10, and an increased expression of a marker of an anti‐inflammatory phenotype arginase II in proximal tubules. L‐cit also restored NO/ROS balance and barrier function in HG‐treated HGEC. Conclusions. L‐cit supplementation is beneficial in preserving the nephron function in STZ‐rodent models. This effect may be due to L‐citrulline’s abilities to establish an anti‐inflammatory response in the proximal tubules and in the circulation. L‐cit also protects the glomerular barrier function from hyperpermeability and NO/ROS imbalance. Grant Funding Source : Supported by NIH HL104126