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L‐citrulline prevents progression of diabetic nephropathy by reducing arginase activity
Author(s) -
Romero Maritza Josefina,
Yao Lin,
Batta Anil,
Lucas Rudolf,
Caldwell Ruth,
Pollock David,
Brands Michael,
Caldwell R. William
Publication year - 2011
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.25.1_supplement.664.16
Subject(s) - arginase , medicine , endocrinology , streptozotocin , diabetic nephropathy , diabetes mellitus , nephropathy , renal function , kidney , excretion , chemistry , arginine , amino acid , biochemistry
Since the role of arginase activity in diabetic nephropathy (DN) remains elusive, we compared DN progression at 2 and 16 wk of diabetes in streptozotocin (STZ)‐induced WT versus arginase II (AII) KO mice. Our data demonstrate that: 1. Renal arginase activity (RAA) and urinary albumin excretion (UAE) are both elevated (8.1 and 6.1 fold of ctrl) at 2 wk of diabetes in WT mice. 2. By 16 wk, RAA in WT mice decreases to 2.7 fold of ctrl, which may reflect a decline in kidney function, since glomerular/tubular collagen deposits are observed in 16 wk, but not 2 wk diabetic mice. 3. UAE increases to 7.7 fold above ctrl at 16 wk. 4. Elevation of RAA correlates with increased AII, but not AI expression in WT STZ‐mice at both 2 and 16 wk. 5. Ctrl and diabetic AII KO mice display reduced RAA levels (0.3 and 0.4 fold) compared to WT ctrl mice. 6. STZ‐AII KO mice have significantly lower UAE (3.5 fold of WT ctrl) and renal collagen deposits than STZ‐WT mice at 16 wk. 7. Treatment of STZ‐WT mice with L‐citrulline (L‐cit, 50 mg/kg/d oral) markedly reduces early elevation in RAA at 2 wk to 2.07 fold of ctrl, with no decay (2.9 fold) at 16 wk. 8. L‐cit reduces elevation of UAE to 1.4 and 2.6 fold of ctrl at 2 and 16 wk of diabetes, respectively, and prevents progression of renal collagen deposits at 16 wk. In summary, AII is involved in DN. L‐cit treatment can prevent or delay the progression of DN, by reducing AII activity. (Supported by JDRF Innov.5‐2009‐468 & R01 NHL70215)