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Geriatric patients show significant variation in how their bodies process medications, which can change how effective and safe treatments are. The liver is the primary organ where drug metabolism occurs, involving two main types of chemical reactions: phase I and II. Phase I metabolism is driven by the cytochrome P450 enzyme system, which includes key types such as CYP3A, CYP2D6, and CYP2C9. Research indicates that while aging doesn't notably alter the levels or activity of these enzymes, it...
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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
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In geriatric patients, renal physiology undergoes significant changes, including diminished renal blood flow and a lower glomerular filtration rate (GFR), leading to alterations in medication clearance. Drugs such as aminoglycoside antibiotics, lithium, and digoxin, which rely on glomerular filtration for removal from the body, particularly impact pharmacokinetics. These drugs tend to have slower clearance rates in older adults, necessitating careful dosage considerations.Evaluation of renal...
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Drug distribution in the human body is influenced by several factors, including plasma protein concentration, body composition, blood flow, tissue-protein concentration, and tissue fluid pH. Among these, changes in plasma protein concentration and body composition due to aging significantly affect how drugs are distributed within the body. Specifically, aging is associated with a decrease in albumin levels by about 10% and an increase in α1-acid glycoprotein levels. These alterations are...
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As individuals age, their body's physiology evolves, affecting drug pharmacokinetics. The most apparent changes occur in the gastrointestinal tract, where an increase in gastric pH, a delay in gastric emptying, and a reduction in gastrointestinal motility are observed. Remarkably, these changes do not substantially modify the absorption of orally administered drugs, particularly those absorbed via passive diffusion.Transdermal drug delivery emerges as a highly viable method for older adults due...
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Age modulates Fe3O4 nanoparticles liver toxicity: dose-dependent decrease in mitochondrial respiratory chain

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Iron oxide nanoparticles (IONPs) impaired mitochondrial function in middle-aged rats but not young rats. This age-specific toxicity suggests caution when using IONPs in older populations.

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Area of Science:

  • Biochemistry
  • Toxicology
  • Nanotechnology

Background:

  • The liver plays a crucial role in iron detoxification.
  • Mitochondrial function is vital for cellular energy production and can be affected by nanoparticles.
  • Aging impacts cellular processes, including mitochondrial activity.

Purpose of the Study:

  • To investigate the effects of iron oxide nanoparticles (IONPs) on liver mitochondrial respiratory chain complexes and coupling in young and middle-aged rats.
  • To determine if age influences the toxicity of IONPs on mitochondrial function.

Main Methods:

  • Isolated liver mitochondria were prepared from young and middle-aged rats.
  • Activities of mitochondrial respiratory chain complexes (I, II, III, IV) and mitochondrial coupling were measured.
  • Mitochondria were exposed to varying concentrations of Fe3O4 nanoparticles.

Main Results:

  • IONPs did not affect mitochondrial function in young rats.
  • In middle-aged rats, IONPs dose-dependently impaired all mitochondrial respiratory chain complexes and reduced mitochondrial coupling.
  • The toxicity was specific to IONPs, as Fe(3+) ions did not cause similar impairment.

Conclusions:

  • IONPs exhibit age-specific toxicity, primarily affecting mitochondrial function in middle-aged rats.
  • These findings highlight potential risks associated with IONP use in older individuals.
  • Caution is advised when considering IONPs for applications involving aging populations.