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.

 Silver nanoparticles (Ag NPs) are widely used in nanomedicine, pharmaceutical products, industry and other consumer products owing to their unique physiochemical properties with probable potential risk to human health and the ecosystems. The aim of this work was to investigate the in-life morphological effects, biochemical, histological and histochemical alterations that might be induced by variable sizes of Ag NPs in hepatic, renal and testicular tissues with the hypothesis that variable sizes of nano-Ag could induce variable effects in the vital organs. Five groups of adult healthy male mice (BALB/C) were exposed to 35 intraperitoneal injections of Ag NPs (1 mg/kg bw) using five different particle sizes (10, 20, 40, 60 and 100 nm). All mice were subjected to in-life morphometric, biochemical, histological and histochemical analysis. The findings demonstrated that Ag NPs could induce alterations in the average body weight gain, food consumption, water intake and organ indices. In addition, these NPs significantly altered hepatic and renal biomarkers. Moreover, Ag NPs produced ground glass hepatocyte cytoplasm, with mitotic activity, nuclear alterations, degeneration, glycogen depletion and inflammatory cells infiltration in the liver. The kidneys of treated mice exhibited proximal renal tubules degeneration, distal renal tubules regeneration, glomerular shrinkage, Bowman’s capsule thickening and interstitial inflammation. The testicular tissues demonstrated spermatocyte sloughing and spermatid giant cell formation. The findings together indicated that Ag NPs could interact with the anatomical structures of the liver, kidney and testis in ways that could induce injury. In addition, the results indicated that smaller Ag NPs posed a greater potential risk than the larger ones, which might be associated with their behaviour, dissolution rate, bioavailability and their probable variable toxicokinetics

Metallic nanoparticles (NPs) are widely used in medical preparations. The present study aims to find out the influence of widely used five metallic NPs on the expression of major hepatic drug-metabolizing enzyme (DME) genes. Six groups of BALB/C mice, 7 mice each, were exposed to: Gold NPs, silver NPs, copper oxide NPs, silicon dioxide NPs and zinc oxide NPs, for 21 days. Liver biopsies from all mice were subjected to mouse cyp3a11, cyp2c29, ugt2b1 and interleukin-6 (il6) gene expression quantification using real-time polymerase chain reaction, in addition to inflammatory cell infiltration examination. All tested NPs caused a sharp and significant (ANOVA, p value < 0.05) downregulation in the expression of DME genes, with the highest influence was observed in mice exposed to copper oxide NPs. Additionally, all NPs induced hepatic inflammation and upregulated the expression of il6 gene, which were inversely correlated with the expression of DMEs. It is concluded that all tested NPs downregulated the expression of DME genes, with the highest influence exhibited by copper oxide NPs, in correlation with inflammation and il6 gene induction in the liver. Further studies are needed to find out the effect of anti-inflammatory compounds against the alterations induced by metallic NPs exposure on hepatic DMEs

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many commercial products, nanomedicine, agriculture, personal care products, different industries and pharmaceutical preparations with potential risk in human health and the environment. The current work was conducted to investigate the renal damage that might be induced by the acute toxicity TiO2 NPs. A total of 40 healthy male adult Wistar albino rats (Rattus norvegicus) were exposed to TiO2 NPs (126, 252, 378 mg/kg bw) for 24 and 48 h. Fresh portions of the kidneys from each rat were processed for histological and histochemical alterations. In comparison with respective control rats, exposure to TiO2 NPs has marked the following glomerular, tubular and interstitial alterations including the followings: glomerular congestion, Bowman's capsule swelling and dilatation, inflamed glomeruli, renal tubules cloudy swelling, karyorrhexis, karyolysis, infiltration of inflammatory cells, congestion, necrosis, hydropic degeneration, dilatation and congestion of blood vessels, hyaline droplets and hyaline casts precipitation, interstitial edema and fibrosis. From the findings of the current work one may conclude that TiO2 NPs are capable of inducing kidney damage with more insulation in the cortex and the proximal convoluted tubules than the medulla and the distal ones respectively. In addition, it might be concluded that renal damage induced by these nanomaterials is dose and duration of exposure dependent. Further hematological, biochemical, immunohistochemical, and ultra-structural studies are recommended

Due to their unique properties, zinc oxide nanoparticles (ZnO NPs) are invested in many industries, commercial products, and nanomedicine with potential risk for human health and the environment. The present study aims to focus on alterations that might be induced by ZnO NPs in the nephron ultrastructure. Male Wister Albino rats were subjected to ZnO NPs at a daily dose of 2 mg/kg for 21 days. Kidney biopsies were processed to transmission electron microscopy (TEM) and ultrastructural pathology examinations. Exposure to ZnO NPs-induced ultrastructural alterations in the proximal convoluted tubules (PCTs) and to lesser extent in the distal ones (DCTs), while the loops of Henle were almost not affected. The glomeruli demonstrated dilatation, partial mesangial cells loss, matrix ballooning, slits filtration widening, and basement membrane thickening. Moreover, PCT revealed cytoplasmic necrosis, vacuolation, erosion, and disorganisation of the apical microvilli together with mitochondrial swelling and cristae destruction. The nuclei of the renal cells exhibited nuclear deformity, heterochromatin accumulation, and apoptotic activities. The findings indicate that ZnO nanomaterial have the potential to affect the nephron ultrastructure suggesting alteration in the kidney functions. More work is needed for better understanding the toxicity and pathogenesis of ZnO oxide nanomaterial.

Due to their unique properties, zinc oxide nanoparticles (ZnO NPs) are invested in many industries, commercial products, and nanomedicine with potential risk for human health and the environment. The present study aims to focus on alterations that might be induced by ZnO NPs in the nephron ultrastructure. Male Wister Albino rats were subjected to ZnO NPs at a daily dose of 2 mg/kg for 21 days. Kidney biopsies were processed to transmission electron microscopy (TEM) and ultrastructural pathology examinations. Exposure to ZnO NPs-induced ultrastructural alterations in the proximal convoluted tubules (PCTs) and to lesser extent in the distal ones (DCTs), while the loops of Henle were almost not affected. The glomeruli demonstrated dilatation, partial mesangial cells loss, matrix ballooning, slits filtration widening, and basement membrane thickening. Moreover, PCT revealed cytoplasmic necrosis, vacuolation, erosion, and disorganisation of the apical microvilli together with mitochondrial swelling and cristae destruction. The nuclei of the renal cells exhibited nuclear deformity, heterochromatin accumulation, and apoptotic activities. The findings indicate that ZnO nanomaterial have the potential to affect the nephron ultrastructure suggesting alteration in the kidney functions. More work is needed for better understanding the toxicity and pathogenesis of ZnO oxide nanomaterial.

Although sertraline is widely prescribed as relatively safe antidepressant drug, hepatic toxicity was reported in some patients with sertraline treatment. The present study was conducted to investigate the morphometric, hepatotoxicity, and change in gene expression of drug metabolizing enzymes. Male healthy adult rabbits (Oryctolagus cuniculus) ranging from 1050 to 1100 g were exposed to oral daily doses of sertraline (0, 1, 2, 4, 8 mg/kg) for 9 weeks. The animals were subjected to morphometric, hepatohistological, histochemical and quantitative real-time polymerase chain reaction analyses. Sertraline chronic exposure induced morphometric changes and provoked histological and histochemical alterations including: hepatocytes hydropic degeneration, necrosis, nuclear alteration, sinusoidal dilation, bile duct hyperplasia, inflammatory cells infiltration, portal vessel congestion, Kupffer cells hyperplasia, portal fibrosis and glycogen depletion. In addition, the gene expression of drug and arachidonic acid metabolizing enzymes were reduced significantly (p value < 0.05). The most affected genes were cyp4a12, ephx2, cyp2d9 and cyp1a2, demonstrating 5 folds or more down-regulation. These findings suggest that chronic sertraline treatment induced toxic histological alterations in the hepatic tissues and reduced the gene expression of drug metabolizing enzymes. Patients on chronic sertraline treatment may be on risk of hepatotoxicity with reduced capacity to metabolize drugs and fatty acids.

Background: Silicon dioxide (silica) nanoparticles (SDNPs) are widely used in nanotechnology and medicine, but these nanomaterials may carry a high risk for human health while little is known about their toxicity. Methods: We investigated the alterations in morphometry, biochemistry, hematology, histology of liver tissue and gene expression of drug-metabolizing enzymes induced by 10-nm SDNPs. Healthy male Wistar albino rats were exposed to 20, 35 and 50 repeated injections of SDNPs (2 mg/kg body weight). Whole blood, serum and plasma samples were used for hematological and biochemical analyses, whereas liver biopsies were processed for histopathological and gene expression alterations. Results: In comparison with control rats, exposure to SDNPs lowered the body weight gain and liver index and increased the counts of white blood cells and platelets, but lowered the platelet larger cell ratio and plateletcrit. Levels of alkaline phosphatase, lactate dehydrogenase, lowdensity lipids, procalcitonin, aspartate aminotransferase and alanine aminotransferase, as well as potassium, phosphorus and iron concentrations, were increased. Histopathology revealed that SDNPs could induce hydropic degeneration, sinusoidal dilatation, hyperplasia of Kupffer cells, karyopyknosis and infiltration of inflammatory cells in the liver. SDNPs reduced the expression of 12 genes of drug-metabolizing enzymes significantly ( p,0.05). Conclusion: These results suggest that SDNPs could cause alterations in morphometry, biochemistry, hematology, liver tissues and the expression of drug-metabolizing enzyme genes.

: Methotrexate (MTX) is widely used in the treatment of some forms of cancer but having severe side effects. The present work aimed to investigate the protective role of propolis treatment against alterations induced by MTX on the hepatic and renal tissues. Rabbits were exposed to MTX (0.25 mg/kg), with or without propolis (50 mg/kg) while hepatic and renal biopsies were examined for histological and histochemical abnormalities. Methotrexate induced hydropic degeneration, pyknosis, sinusoidal dilatation and bile duct hyperplasia in the liver together with renal tubular degeneration, glomerular shrinkage and hyaline droplet precipitation. While propolis partially ameliorated some of the morphometric and biochemical alterations, none of the hepatic alterations induced by MTX was protected by propolis treatment. Nevertheless glomerular shrinkage and renal tubule degeneration were partially protected in animals received both MTX plus propolis. It is concluded that propolis treatment has little or no ameliorative effect in protecting the hepatic and renal tissues from MTX toxicity.

OBJECTIVE: To investigate the histomorphometric alterations induced in testicular tissues by variable sizes of silver nanoparticles (SNPs). STUDY DESIGN: Male mice (BALB/C) were treated with SNPs (1 mg/kg) using 5 different sizes (10, 20, 40, 60, and 100 nm) for 35 days. Testicular biopsies from all mice under study were examined histomorphologically. RESULTS: SNPs sized 10 and 20 nm had provoked morphometric changes in the testes of the subjected mice together with the following histological alterations: seminiferous tubules, degeneration, spermatocyte cytoplasmic vacuolation, spermatocyte sloughing, and spermatid giant cell formation. Larger SNPs (40, 60, and 100 nm) induced little or no testicular histomorphometric alterations. CONCLUSION: The findings of the present work may indicate that subchronic exposure to SNPs could have a deleterious impact on the testicular tissues and spermatogenic process that could affect fertility and reproduction, with smaller SNPs being more toxic than larger ones.