Abstract |
The 12/ 15-lipoxygenase (12/15-LO) pathway is activated in diabetes mellitus (DM), increasing 12(S)-hydroxyeicosatetraenoic acid (12-HETE). We showed that a 12-LO inhibitor, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (CDC) inhibited 12/15-LO activity in vivo and assessed the efficacy of another 12/15-LO inhibitor, N-benzyl-N-hydroxy-5-phenylpentamidine ( BHPP), to diminish urinary 12-HETE and ameliorate diabetic nephropathy (DN) over 4 months. Rats studied were control (C, n=8), DM (n=6), and rats injected with BHPP (C+BHPP, n=4) and (DM+BHPP, n=5). BHPP 3 mg/kg/day decreased urinary (U) 12- HETE/ creatinine (cr) by 30-50% after one injection and after 1 week of daily injections in DM rats. U 12- HETE/cr excretion increased paradoxically in controls given BHPP. There was a highly significant relationship between U 12- HETE/cr excretion and U alb/cr (r=0.79, P<10(-5)), demonstrating that renal 12/15-LO pathway activation is associated with albuminuria. BHPP did not inhibit glomerular collagen synthesis or improve histology. More sustained 12-LO inhibition may improve albuminuria in DN.
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Authors | Jun Ma, Rama Natarajan, Janine LaPage, Linda Lanting, Nancy Kim, Diana Becerra, Breyon Clemmons, Cynthia C Nast, G K Surya Prakash, Mihirbaran Mandal, Sharon G Adler |
Journal | Prostaglandins, leukotrienes, and essential fatty acids
(Prostaglandins Leukot Essent Fatty Acids)
Vol. 72
Issue 1
Pg. 13-20
(Jan 2005)
ISSN: 0952-3278 [Print] Scotland |
PMID | 15589395
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Amides
- Benzylamines
- Caffeic Acids
- Collagen Type IV
- Lipoxygenase Inhibitors
- cinnamyl-3,4-dihydroxycyanocinnamate
- N-benzyl-N-hydroxy-5-phenylpentamide
- 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
- Creatinine
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Topics |
- 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
(urine)
- Albuminuria
- Amides
(pharmacology)
- Animals
- Benzylamines
(pharmacology)
- Caffeic Acids
(pharmacology)
- Collagen Type IV
(metabolism)
- Creatinine
(urine)
- Diabetic Nephropathies
(drug therapy, enzymology)
- Kidney Glomerulus
(drug effects, pathology)
- Lipoxygenase Inhibitors
(pharmacology)
- Male
- Rats
- Rats, Sprague-Dawley
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