Clearance Pathways and Tumor Targeting of Imaging Nanoparticles *
Valerio Voliani in Nanomaterials and Neoplasms, 2021
Excretion is an essential biological process that prevents damage and toxicity by eliminating unwanted materials from the body. There are two major excretion routes: the renal (urine) and hepatic (bile to feces) pathways for contrast agents. In general, renal excretion is preferred because the contrast agents can be rapidly eliminated while little cellular internalization/metabolism is involved, thus effectively minimizing body exposure to the contrast agents. The renal pathway relies on glomerular filtration in the kidneys; thus, the material size, charge, and shape all affect the filtration efficiency. The filtration-size threshold of glomerular capillary walls is typically 6–8 nm for spherical particles (size-, charge-, and surface ligand-dependent within this range),14 indicating renal excretion is exclusive only for materials with ultrasmall hydrodynamic diameters (HDs).
An Overview of Drug-Induced Nephropathies *
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
Drug-induced nephropathies are common, numerous, and often underdiagnosed. Little known only 30 years ago, they now have an important place in nephrology. In fact, that drugs may be responsible should now be considered in every type of renal failure, whether acute or chronic, glomerular, tubular, interstitial, or vascular. The kidney is a particularly vulnerable organ. It is highly vascularized, receiving 25% of cardiac output, and contact surfaces between the nephron structures and a xenobiotic are extensive, both for the glomerular endothelium and the surface of the tubular epithelium. The kidney has many functions, one of which is mainly the excretion of waste. It also plays a determinant role in homeostasis of the milieu interieur, and it is capable of diluting or concentrating urine in relation to the plasma. The concentrating capacity of the kidney may have deliterious consequences when it leads to the accumulation of toxic substances in the renal interstitium. Being the site of numerous metabolic transformations, the kidney requires normal perfusion, sufficient energy-producing substances, and constant oxygen supply. The kidney is also sensitive to insult from the exterior.
Structure, Function, Type, and Sensitivity of Skin
Frank C. Powell, Jonathan Wilkin in Rosacea: Diagnosis and Management, 2008
Excretion (of water and sodium chloride and probably other materials) takes place through the skin, but there has been little research focused on this aspect of skin function to date. Some naturopathic physicians and nutritionists believe that cutaneous elimination of “toxins” is an important skin function. They suggest that defective cutaneous excretion of toxic substances can lead to the inflammatory changes in the skin of patients with both acne vulgaris and rosacea. As already indicated vitamin D synthesis takes place in the skin. Activated vitamin D has recently been shown to have a role in the regulation of antimicrobial peptides (AMPs) and may be significant in the pathogenesis of rosacea as it appears that some such peptides (cathelicidins) are abnormally processed and may lead to inflammation in the skin.
Aluminum oxide nanoparticles mediated toxicity, loss of appendages in progeny of Drosophila melanogaster on chronic exposure
Published in Nanotoxicology, 2019
Avnika Singh Anand, Urmila Gahlot, Dipti N. Prasad, Ekta Kohli
Digestive tract not only provides absorption of nutrients and excretion of waste but also immunological protection against infection (Zhang et al. 2014). The excretion system ensures removal of unwanted waste. However, these important systems are vulnerable to various environmental toxins. Zinc oxide nanoparticles are reported to cause digestive toxicity (Wang et al. 2008). Glomerular swelling and histopathology are reported in mice exposed to TiO2 NPs (Chen et al. 2009). Kidney is less sensitive to nanotoxicity, however, exposure CuO nanoparticles cause renal toxicity (Chen et al. 2006). In this study, we have clearly observed renal failure on exposure to Al2O3 NPs as demarcated by swollen abdomen in flies. LC/MS/MS shows altered protein expression level of proteins like actin, myosin, laminin related to digestive tract morphogenesis. Laminins are involved in morphogenesis of most of the vital organs including gut and Malpighian tubules (Urbano et al. 2009). The alteration of the protein profile can be the possible cause of swollen abdomen showing renal failure in progeny flies.
Pharmacotherapy options and drug development in managing periprosthetic joint infections in the elderly
Published in Expert Opinion on Pharmacotherapy, 2019
Alicia Macias-Valcayo, Bernadette G Pfang, Alvaro Auñón, Jaime Esteban
Although drugs are eliminated from the body in a number of ways, the main organ involved in excretion is the kidney. With age, overall kidney function decreases [71]. Decreased renal blood flow and glomerular filtration reduce the clearance of kidney-eliminated drugs. Reduced renal clearance of antimicrobials is directly proportional to increases in half-life. Increased half-life requires a decrease in daily doses to prevent toxicity and prolongs the time necessary to achieve steady-state serum concentrations. However, administering loading doses of vancomycin is a secure approach, which does not increase the incidence of nephrotoxicity [72]. It is important to take this into account when using antibiotics with narrow therapeutic indices (the ratio of effective to toxic serum concentrations) that require serum concentration monitoring [73], and in some cases, drug dosing must be based on renal function [74].
Cetuximab-conjugated PLGA nanoparticles as a prospective targeting therapeutics for non-small cell lung cancer
Published in Journal of Drug Targeting, 2023
Leena Kumari, Iman Ehsan, Arunima Mondal, Ashique Al Hoque, Biswajit Mukherjee, Pritha Choudhury, Arunima Sengupta, Ramkrishna Sen, Prasanta Ghosh
The liver and kidney are the two crucial organs involved in the body’s primary metabolism and excretion, respectively. As a result, aberrant liver and kidney functions are thought to be a sign of clinical symptoms, making the biochemical parameters that regulate the functions of these organs as a promising therapeutic target. The results of this study showed that the liver and kidney toxicity markers, ALP, SGPT, SGOT, urea, and creatinine, of the experimental mice treated with various nanoformulations revealed that levels of toxicity were in the order of DTX > DTX NP > Cet-DTX NP for a maximum dose, 40 mg/kg (Table S5). Moreover, no substantial alterations in the body weight of normal mice treated with DTX NP and Cet-DTX NP were observed up to the dose of 10 mg/kg body weight, as compared to free DTX which showed a marked change in body weight after the dose was increased to 10 mg/kg body weight (Table S6). Comparatively higher toxicity of free DTX, DTX NP, and Cet-DTX NP in normal mice was observed when the dose of the drug was increased from 20 to 40 mg/kg body weight.