China
Africa
Explore chapters and articles related to this topic
Mitochondrial Mechanisms of Tubular Injury
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Rick G. Schnellmann, Richard D. Griner
The factors which make the kidney a select target of any toxic compound include extensive accumulation, metabolic activation, and/or functional targeting. The reabsorptive and secretory capacities of renal tubules may result in extensive accumulation of compounds within the tubular cells. This accumulation plays a critical role in the nephrotoxicity of each of the compounds discussed below. Following accumulation, compounds may be metabolically activated to toxic species within the renal cell as occurs for the haloalkene and haloalkane cysteine conjugates. Additionally, selective impairment of a function which is critically important to the cell facilitates the cytotoxic response to many nephrotoxicants. This is particularly true for renal mitochondrial functions because renal tubular cells derive the majority of their energy from oxidative phosphorylation.
Apoptotic Cell Death in Response to Lipopolysaccharide
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Renal tubular cells in kidneys of GSR-induced mice were stained positively by the in situ specific labeling of fragmented DNA. The positive staining of renal tubules was focal. It was suggested that apoptotic cell death might also participate in the development of acute tubular necrosis in GSR. Simultaneous administration of anti-IFN-γ antibody in the injection of LPS significantly blocked apoptosis of renal tubular cells. Priming with recombinant IFN-γ in replacement of LPS could produce apoptosis of tubular cells as well as vascular endothelial cells. IFN-γ might play a critical role in the sensitization of renal tubular cells for LPS-induced apoptosis. The provocative injection of TNF-α in replacement of LPS produced marked apoptosis of tubular cells in LPS-primed mice. The intensity of the apoptosis induced by TNF-α in replacement of LPS was more marked. Therefore, effector molecules for apoptosis of tubular cells might be TNF-α. This was supported by the finding that priming of mice with LPS resulted in the expression of TNF receptors on tubular cells. ICAM-1 was also expressed on renal tubular cells in GSR-induced mice. However, the role of ICAM-1 in the induction of apoptosis of tubular cells was still unclear.
Mitochondrial encephalomyelopathy, lactic acidosis, and stroke-like episodes (MELAS)
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Renal involvement may take the form of renal tubular acidosis, and there may be a typical renal Fanconi syndrome [39]. One patient developed a nephrotic syndrome and had focal glomerulosclerosis [16]. A variety of other organs have been involved in individual patients. One had pancreatitis following valproate administration [15]. Others have had peripheral neuropathy with or without rhabdomyolysis [40]. The histologic signature of the MELAS syndrome is the appearance of ragged red fibers in the muscle (Figure 51.8) [1, 12, 13, 37]. These are best seen in the trichrome stain. In H&E, there may be variation in fiber size and increase in connective tissue. Staining with periodic acid Schiff (PAS), NADH tetrazolium reductase, or for succinic dehydrogenase may show increased subsarcolemmal activity. Electron microscopy reveals an increase in number and size of mitochondria (Figure 51.9), some with paracrystalline inclusion bodies [13, 37].
Targeted drug delivery strategy: a bridge to the therapy of diabetic kidney disease
Published in Drug Delivery, 2023
Xian Chen, Wenni Dai, Hao Li, Zhe Yan, Zhiwen Liu, Liyu He
Glomerular basement membrane (GBM) thickening is considered as the earliest observed pathological feature in patients with DKD, which is appeared within 1–2 years after the onset of DM (Tervaert et al., 2010; Ponchiardi et al., 2013). Endothelial cells play an important role in the progression of DKD. With the development of DKD, the fenestrated ECs are decreased in diabetic patients, which correlates with albuminuria and the loss of GFR (Dou and Jourde-Chiche, 2019). Mesangial expansion, caused by Mesangial cells (MCs) enlargement and accumulation of glomerular matrix protein, is the most common renal pathological change in DKD (Reidy et al., 2014; Zhang et al., 2019). On the glomerular capillary side of MCs, without the surrounding of GBM and podocytes, drugs can be delivered to MCs for treating kidney diseases (Scindia et al., 2008). Podocytes are glomerular epithelial cells which contain 3 separate elements: cell body, extending processes and foot processes (Garg, 2018). Podocytes injury in DKD is induced by many compound factors, such as inflammatory reaction, mechanical stress, oxidative stress, renin angiotensin aldosterone system activation, TGF-β1 induction, and AGEs accumulation, and any part of the pathway is expected to be the target of DKD therapy (Kawanami et al., 2016). The renal tubules consist of the proximal tubules, collecting tubules and distal tubules. The morphological and functional changes of the renal tubules are involved in the pathogenesis and progression of DKD (Duan et al., 2021). Most renal tubular targeted systems are directed at the proximal tubules (Christensen et al., 2012).
Oxidative stress and histopathological changes in several organs of mice injected with biogenic silver nanoparticles
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Shushanik Kazaryan, Lilit Farsiyan, Juleta Tumoyan, Gayane Kirakosyan, Naira Ayvazyan, Hrachik Gasparyan, Sona Buloyan, Lilit Arshakyan, Ara Kirakosyan, Ashkhen Hovhannisyan
The parameter of inflammation of portal tracts in this group was significantly higher compared to mice that were exposed to O. araratum (p < .05). There were also acute congestion, hemostasis and sinusoidal dilation observed in this group. These parameters were significantly lower compared to the mice that were administered with O. araratum (p < .05). After the exposure to AgNPs, in the renal tissue, a process of acute tubular necrosis is revealed. Epithelial cells of the renal tubules were detached from the basal lamina and localized in the lumen of the tubules. In some areas, the cytoplasm of the proximal and distal renal tubules is vacuolated. The glomeruli were mostly preserved, but in some areas, there were early processes of glomerulosclerosis with mesangial cell proliferation (Figure 8). Statistical analysis of mesangial proliferation, parenchymal inflammation and signs of acute tubular necrosis showed significant pathological changes compared to control (p < .05), but there were no significant differences observed between AgNPs and O. araratum. Thus, the revealed morphological alterations are apparently associated with the toxic effects of the tested substances.
Ascorbic acid and hydrocortisone synergistically inhibit septic organ injury via improving oxidative stress and inhibiting inflammation
Published in Immunopharmacology and Immunotoxicology, 2022
Yuan-yuan Xu, Cheng-zhu Xu, You-feng Liang, Dan-qun Jin, Jie Ding, Yao Sheng, Le Zhang, Fang Deng
Kidney and liver tissues were harvested from the sacrificed mice, then samples were postfixed in 4% paraformaldehyde overnight at 4 °C. Tissues were embedded in paraffin after dehydration and sliced into 5 μm sections. Sections were finally stained with hematoxylin and eosin (H&E) and observed by light microscopy (×200, Olympus, TKY, Japan). The degree of pathological injury in liver tissues was scored based on a previously published report [10]: 0, normal rectangular structure; 1, rounded hepatocytes with an increase in the sinusoidal spaces; 2, vacuolization; 3, nuclear apoptosis with inflammatory cell infiltration; 4, necrosis. Moreover, pathological changes were scored [11] by the percentage of damaged renal tubules, as indicated by tubular lysis, dilation, disruption, and cast formation. Tissue damage was scored on a scale of 0–4, with 0, 1, 2, 3, and 4 corresponding to 0%, <25%, 26%–50%, 51%–75%, and ≥76% of injured renal tubules, respectively. Histological evaluations were performed by an experienced pathologist who was unaware of the group details.