1. 12/15-lipoxygenase inhibitors in diabetic nephropathy in the rat
- Author
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Nancy Kim, Jun Ma, Sharon G. Adler, Janine LaPage, Rama Natarajan, Breyon Clemmons, Cynthia C. Nast, Linda Lanting, Diana Becerra, Mihirbaran Mandal, and G.K. Surya Prakash
- Subjects
Collagen Type IV ,Male ,medicine.medical_specialty ,Benzylamines ,Urinary system ,Clinical Biochemistry ,Kidney Glomerulus ,Diabetic nephropathy ,Excretion ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Caffeic Acids ,In vivo ,Internal medicine ,Diabetes mellitus ,medicine ,Albuminuria ,Animals ,Diabetic Nephropathies ,12-Hydroxy-5,8,10,14-eicosatetraenoic Acid ,Lipoxygenase Inhibitors ,Creatinine ,business.industry ,Cell Biology ,medicine.disease ,Amides ,Rats ,Endocrinology ,chemistry ,medicine.symptom ,business ,Kidney disease - 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
- Published
- 2004