Biomaterial Database

Effect of clofibrate on fatty acid metabolism in the kidney of puromycin-induced nephrotic rats. 2016

Yoshikazu Muroya, and Osamu Ito

Department of General Medicine and Rehabilitation, Tohoku Medical and Pharmaceutical University School of Medicine, 1-12-1 Fukumuro, Miyagino-ku, Sendai, 983-8512, Japan. ymuroya@hosp.tohoku-mpu.ac.jp.

BACKGROUND Proteinuria plays an essential role in the progression of tubulointerstitial damage, which causes end-stage renal disease. An increased load of fatty acids bound to albumin reabsorbed into proximal tubular epithelial cells (PTECs) contributes to tubulointerstitial damage. Fibrates, agonists of peroxisome proliferator-activated receptor α (PPARα), have renoprotective effects against proteinuria whereas the effects of these compounds on fatty acid metabolism in the kidney are still unknown. Therefore, the present study examined whether the renoprotective effects of clofibrate were associated with improvement of fatty acid metabolism in puromycin aminonucleoside (PAN)-induced nephrotic rats. METHODS Rats were allocated to the control, PAN or clofibrate-treated PAN group. Biochemical parameters, renal injury and changes in fatty acid metabolism were studied on day14. RESULTS PAN increased proteinuria, lipid accumulation in PTECs, excretions of N-acetyl-β-D-glucosaminidase (NAG) and 8-hydroxydeoxyguanosine (8OHdG) and the area of caspase 3-positive tubular cells. It decreased renal expressions of medium-chain acyl-CoA dehydrogenase (MCAD), cytochrome P450 (CYP)4A, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and estrogen-related receptor α (ERRα) without change of the expression of PPARα. Clofibrate reduced proteinuria, lipid accumulation, NAG excretion and the area of caspase 3-positive tubular cells. However, albumin excretion was not reduced and 8OHdG excretion was increased. Clofibrate minimized changes in MCAD, CYP4A, PGC-1α and ERRα expressions with increased PPARα, very long-chain acyl-CoA dehydrogenase (VLCAD) and long-chain acyl-CoA dehydrogenase (LCAD) expressions. CONCLUSIONS Clofibrate is protective against renal lipotoxicity in PAN nephrosis. This study indicates that clofibrate has renoprotective effects through maintaining fatty acid metabolism in the kidney of PAN-induced nephrotic rats.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D007678	Kidney Glomerulus	A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.	Glomerulus, Kidney
D008297	Male		Males
D009404	Nephrotic Syndrome	A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.	Childhood Idiopathic Nephrotic Syndrome,Frequently Relapsing Nephrotic Syndrome,Multi-Drug Resistant Nephrotic Syndrome,Pediatric Idiopathic Nephrotic Syndrome,Steroid-Dependent Nephrotic Syndrome,Steroid-Resistant Nephrotic Syndrome,Steroid-Sensitive Nephrotic Syndrome,Multi Drug Resistant Nephrotic Syndrome,Nephrotic Syndrome, Steroid-Dependent,Nephrotic Syndrome, Steroid-Resistant,Nephrotic Syndrome, Steroid-Sensitive,Nephrotic Syndromes,Steroid Dependent Nephrotic Syndrome,Steroid Resistant Nephrotic Syndrome,Steroid Sensitive Nephrotic Syndrome,Steroid-Dependent Nephrotic Syndromes,Steroid-Resistant Nephrotic Syndromes,Steroid-Sensitive Nephrotic Syndromes,Syndrome, Nephrotic,Syndrome, Steroid-Sensitive Nephrotic
D011691	Puromycin	A cinnamamido ADENOSINE found in STREPTOMYCES alboniger. It inhibits protein synthesis by binding to RNA. It is an antineoplastic and antitrypanosomal agent and is used in research as an inhibitor of protein synthesis.	CL-13900,P-638,Puromycin Dihydrochloride,Puromycin Hydrochloride,Stylomycin,CL 13900,CL13900,P 638,P638
D011960	Receptors, Estrogen	Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.	Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
D002994	Clofibrate	A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)	Athromidin,Atromid,Atromid S,Clofibric Acid, Ethyl Ester,Ethyl Chlorophenoxyisobutyrate,Miscleron,Miskleron,Chlorophenoxyisobutyrate, Ethyl
D005227	Fatty Acids	Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)	Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D000097983	ERRalpha Estrogen-Related Receptor	An orphan nuclear receptor that belongs to the ERR subfamily. It has enriched expression in tissues with high oxidative metabolic capacity.	ERR1 Protein,Estrogen-Related Receptor 1,Estrogen-Related Receptor alpha,ERRalpha
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia