Renal Alterations Induced by Chronic Exposure to Therapeutic Doses of Antihypercholestremic Atorvastatin

Background: Atorvastatin (ATOR) is widely used for the treatment and prevention of hypercholesterolemia and various diseases, such as cardiovascular complication, with little data about the histopathological and ultrastructural renal alterations that might be induced by this drug. Objectives: The present study was undertaken to investigate the potential toxicity of therapeutic doses of atorvastatin on the microanatomy and ultrastructure of renal tissues from Wistar albino rats. Methods: Adult male Wistar albino rats received an oral daily dose of 5 mg/kg body weight for 90 consecutive days. Biopsies from both kidneys of each study rat were taken for histopathological and ultrastructural examination. Results: ATOR-treated rats exhibited glomerular, tubular, and interstitial histological alterations, including degeneration, necrosis, hyaline droplets, edema, cortical hemorrhages, mesangial hypercellularity, and blood capillary dilation and congestion. In addition, ATOR exposure increased the activity of glucose-6-phosphate dehydrogenase and alkaline phosphatase with a concurrent reduction in proteins and neutral mucosubstances content of the glomeruli and renal cells. Moreover, ATOR-treated animals demonstrated glomerular ultrastructural alterations, consisting mainly of capillary tuft dilatation, glomerular basement membrane thickening, and mesangial cell proliferation. The renal cells of the proximal tubules demonstrated damaged mitochondria, degenerative cellular changes, endoplasmic reticulum dilatation, lysosomal and autophagosome activation, nuclear alteration, myelin figure formation, and microvilli disorganization. Conclusion: The findings of the present work may indicate that ATOR can induce renal histological, histochemical, and ultrastructural alterations that may affect kidney and other vital organ function.

Ochratoxin a and Citrinin Induced Nephrosis in Beagle Dogs III. Terminal Renal Ultrastructural Alterations

The extent and type of renal ultrastructural changes in Beagle dogs varied with the administration of ochratoxin A and citrinin alone and in the two dosage combinations. The three predominant changes were cytoplasmic vacuolation, myelin figure formation and lesions designated as cytoplasmic disarray. These changes were mainly of the endomembrane system of the tubular epithelial cells. Cytoplasmic vacuoles were within proximal and distal tubules and collecting ducts and were most numerous in dogs given 10 mg/kg citrinin. Vacuolation of similar distribution, but less severe, was seen in renal tubular cells of dogs given the higher dose of the combined mycotoxins (0.2 mg/kg ochratoxin A + 10 mg/kg citrinin). This damage was limited to the proximal tubular cells in dogs given only ochratoxin A (0.1 or 0.2 mg/kg). Myelin figures were in proximal epithelial cells of dogs given ochratoxin A alone or combined with citrinin. There was cytoplasmic disarray in dogs of all groups except for dogs given 5 mg/kg citrinin. This lesion was usually limited to the proximal tubules. The lesion, however, was found in cells of the distal tubules of dogs given 10 mg/kg citrinin alone.

Scanning and Transmission Electron Microscopy of Endomentrium in Women Wearing TCu-380-A IUD 's

Recent ultrastructural studies on endometrial tissues from women wearing copper, wire intrauterine devices have disclosed morphological evidence of impaired glycogen degradation and secretion resulting in interference with the viability of blastocysts. Reduced microapocrine secretion observed with the scanning electron microscope supports this (1). In addition, organelle modifications have been observed in the epithelial cells of these women. The changes are seen in biopsies taken in the proliferative phase of the cycle and consist of mitochondrial vacuolation and myelin figure formation. These modifications disappear in the secretory phase and therefore have been regarded as reversible (2).The aim of the present studies was to investigate surface epithelial changes as well as organelle modifications in relation to the site of contact with an IUD that releases greater amounts of copper. Endometrial tissue was obtained from the uterine cavity of four young women wearing TCu-380-A intrauterine contraceptive devices for 4-6 weeks.