| Literature DB >> 15589395 |
Jun Ma1, Rama Natarajan, Janine LaPage, Linda Lanting, Nancy Kim, Diana Becerra, Breyon Clemmons, Cynthia C Nast, G K Surya Prakash, Mihirbaran Mandal, Sharon G Adler.
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.Entities:
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Year: 2005 PMID： 15589395 DOI： 10.1016/j.plefa.2004.06.004
Source DB: PubMed Journal: Prostaglandins Leukot Essent Fatty Acids ISSN： 0952-3278 Impact factor: 4.006