Essential fatty acid deficiency normalizes function and histology in rat nephrotoxic nephritis.
The central lipid abnormality in essential fatty acid deficiency (EFAD) is the lack of availability of arachidonic acid. To examine the role of total eicosanoid's biosyntheses in the pathology and pathophysiology of glomerulonephritis, EFAD was induced in weanling rats, which were then subjected to antiglomerular basement membrane antibody (NTS)-induced injury in adulthood. Glomerular dynamics (as assessed by micropuncture), quantitative histology, and eicosanoid generation rates were measured at two hours and two weeks post-NTS, and compared to those of standard diet-fed (STD) controls. Two hours post-NTS, and despite the occurrence of proteinuria in both EFAD and STD animals, glomerular dynamics were essentially normal in EFAD rats, whereas STD animals had reduced values for glomerular filtration rate (GFR) and renal plasma flow rate (RPF). At two weeks, severe histologic changes were observed in STD animals including mesangial and stalk hypercellularity, moderate sclerosis, and interstitial nephritis, coupled with heavy proteinuria and reduced GFR and RPF. In dramatic contrast, EFAD rats displayed totally normal glomerular structures and functions. In parallel, glomerular generation rates of prostaglandin E2 and thromboxane A2 were suppressed markedly in EFAD rats. Thus, EFAD confers complete protection against the histopathologic and functional sequelae of immune-initiated injury in the glomerulus. The data suggest that the initial wave of complement-induced neutrophil infiltration (with resultant proteinuria) is not sufficient to perpetuate injury into the more destructive chronic phases. The results provide strong impetus for the design of more specific interventional therapies targeting the various enzymes and products of arachidonic acid metabolism in the attempts to control glomerular inflammation.
Takahashi
K
K
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
Kato
T
T
Schreiner
G F
GF
Ebert
J
J
Badr
K F
KF
D000208:Acute Disease; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002908:Chronic Disease; D015777:Eicosanoids / Q000096:biosynthesis; D005228:Fatty Acids, Essential / Q000172:deficiency*; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation
D015777:Eicosanoids; D005228:Fatty Acids, Essential; D016718:Arachidonic Acid