Postmortem redistribution of drugs: a literature review.

Postmortem drug analysis is crucial in identifying the potential cause and manner of death. However, it is threatened by a significant phenomenon called postmortem redistribution (PMR), which refers to the alterations in drug levels occurring after death. This review aims to describe the PMR phenomenon, the mechanisms involved in the PMR of drugs, the various methods used to predict it, and various artifacts of postmortem drug concentrations. Several mechanisms, including passive diffusion from solid organs that act as drug reservoirs to the surrounding tissues, cadaveric changes after death (e.g., cell death, blood coagulation, hypostasis, and movements), and the putrefactive process, can result in artifacts of postmortem drug concentrations. The drug's chemical and pharmacokinetic properties (such as acidic/basic properties, lipophilicity, protein binding, high volume of distribution, and residual metabolic activity) are additional factors. Several markers, including cardiac blood-to-peripheral blood ratio (C/P), liver-to-peripheral blood ratio (L/P), amino acid markers such as methionine, quantitative structure-activity relationship (QSAR) approach, and F factor, have been proposed for interpreting the liability of drugs to PMR. Several artifacts may affect the reliability of postmortem drug analysis. Peripheral blood is preferred for postmortem drug sample collection. Numerous laboratories evaluate the redistribution potential of drugs after death using the C/P concentration ratio. Nevertheless, the L/P concentration ratio is proposed to be a more reliable marker for PMR determination.

Histological and biochemical evaluation of the effects of silver nanoparticles (AgNps) versus titanium dioxide nanoparticles (TiO2NPs) on rat parotid gland.

The unlimited use of nanoparticles (NPs) results in toxic impacts on different tissues. The current study aimed to compare the adverse effects of AgNPs and TiO2NPs on the parotid gland of adult male albino rats as regards the histopathological, immunohistochemical, and biochemical changes, exploring the possible underlying mechanisms and the degree of improvement after cessation of administration. Fifty-four adult male albino rats were divided into control group (I), AgNPs-injected group (II), and TiO2NPs-injected group (III). We measured the levels of tumor necrosis factor-alpha (TNF-α) and interleukin (IL-6) in the serum, and levels of MDA and GSH in parotid tissue homogenate. Quantitative real-time polymerase-chain reaction (qRT-PCR) was used to measure the expression levels of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1-α), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), mouse double minute 2 (MDM2), Caspase-3 Col1a1, and Occludin. Parotid tissue sections were examined by light microscope (Hematoxylin & Eosin and Mallory trichrome stains), electron microscope, and immunohistochemical examination of CD68 and anti-caspase-3 antibodies. Both NPs severely affected the acinar cells and damaged the tight junction between them by enhancing expression of the inflammatory cytokines, inducing oxidative stress, and disturbing the expression levels of the studied genes. They also stimulated fibrosis, acinar cell apoptosis, and inflammatory cells infiltration in parotid tissue. TiO2NPs effects were less severe than AgNPs. Cessation of exposure to both NPs, ameliorated the biochemical and structural findings with more improvement in TiO2NPs withdrawal. In conclusion: AgNPs and TiO2NPs adversely affected the parotid gland, but TiO2NPs were less toxic than AgNPs.

Electric field-directed migration of mesenchymal stem cells enhances their therapeutic potential on cisplatin-induced acute nephrotoxicity in rats.

Cisplatin is widely used as an anti-neoplastic agent but is limited by its nephrotoxicity. The use of mesenchymal stem cells (MSCs) for the management of acute kidney injury (AKI) represents a new era in treatment but effective homing of administered cells is needed. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on cisplatin-induced AKI in rats after directed migration by electric field (EF). Forty-eight adult male albino rats were equally classified into four groups: control, cisplatin-treated, cisplatin plus BM-MSCs, and cisplatin plus BM-MSCs exposed to EF. Serum levels of IL-10 and TNF-α were measured by ELISA. Quantitative real-time PCR analysis for gene expression of Bcl2, Bax, caspase-3, and caspase-8 was measured. Hematoxylin and eosin (H&E) staining, periodic acid Schiff staining, and immunohistochemical analysis were also done. MSC-treated groups showed improvement of kidney function; increased serum levels of IL-10 and decreased levels of TNF-α; and increased mRNA expression of Bcl2 and decreased expression of Bax, caspase-3, and caspase-8 proteins comparable to the cisplatin-injured group. EF application increased MSCs homing with significant decrease in serum urea level and caspase-3 gene expression together with significant increase in Bcl2 expression than occurred in the MSCs group. Restoration of normal kidney histomorphology with significant decrease in immunohistochemical expression of caspase-3 protein was observed in the BM-MSCs plus EF group compared to the BM-MSCs group. EF stimulation enhanced the MSCs homing and improved their therapeutic potential on acute cisplatin nephrotoxicity.