Ultrastructural Changes of the Glomeruli of the Rat Induced by Indomethacin

Abstract

Since indomethacin diminishes the intensity of proteinuria in glomerulonephritis, experiments were undertaken to identify the morphological elements that might explain the reduction in the permeability of the glomerular capillary wall. In normal rats, the treatment with indomethacin produced first of all in the podocytes morphological signs of a possible activated function and in later stages a reaction of mesangial cells. The possible role of these two types of cells in the production of the basal membrane of the glomerular capillary, and the significance that their ‘activated function’ may have on the permeability of the capillary wall are discussed.

Aminonucleoside Nephrosis in Rats

“…In rats treated for 5 days only with Indomethacin there was a marked hyper trophy of the podocytes with the characteristic cytoplasmic changes, previ ously described by us [34]: increase in the number of polysomes, mitochondria, and membranes of rough endoplasmic reticulum often containing character istic inclusions, roundish in shape, formed by an electron-dense ground sub stance and a ribbon-like component of greater electron density; enlargement of Golgi apparatus with numerous vesicles full of electron-dense material; centrioles, and numerous microtubuls and multivesicular bodies ( fig. 3).…”

“…However, we have hypothesized that this drug may be able to reduce the glomerular capillary permeability also increasing the synthesis of basement membrane material by podocytes [34]. It seemed to us that the experimental model more suitable to confirm our supposition was the aminonucleoside nephrotic syn drome; in fact, although its pathogenesis is not yet understood, certainly it is not correlated with intravascular coagulation and/or to granulocytic chemotaxis.…”

“…Rats treated with aminonucleoside (12 days) and Indomethacin (5 days) showed the characteristic ultrastructural changes of podocytes induced by Indomethacin (in particular, the peculiar cytoplasmic inclusions interpreted as 'basement membrane material') [34], Moreover, the fusion of foot processes was less evident and the specific podocytic alterations of the aminonucleoside nephrotic syndrome were less conspicuous ( fig.4,5).…”

“…Indomethacin may modify permeability of the glomerular capillary wall by a protective action on the granulocytic lysosomes [2], a negative leukocytic chemotaxis [26], and a reduction of platelet aggregation [5,25], However, on the basis of our previous work [34], we have put forward the hypothesis that Indomethacin may produce a reduction in the permeability of the glomerular capillary wall, through an increased synthesis of the basement membrane by podocytes. We found of interest to study the effects of Indomethacin on rats treated with aminonucleoside.…”

Effect of Indomethacin on the Synthesis of Glomerular Basement Membrane and on Proteinuria in Rats with Nephrotoxic Nephritis

“…indomethacin on platelet aggregation [5], leukocyte chemotaxis [6], granulocyte lysozomes [7], and glomerular basement mem brane (GBM) synthesis [8]. The purpose of this study was to determine whether the in fluence of indomethacin on protein excretion in rats with nephrotoxic nephritis (NTN) is mediated by an effect of indomethacin on the synthesis of GBM.…”