Erythrocyte‐aniune interaction leads to their accumulation and iron deposition in rat spleen

Abstract

In order to understand the splenic toxicity of aniline in rats, early interaction of aniline with erythrocytes and its subsequent deposition and covalent binding to macromolecules in target (spleen) and nontarget (liver) organs have been studied. Male Sprague-Dawley (SD) rats were given 1 or 3 doses of 1 mmol/kg [14C]aniline hydrochloride (1 dose/d) by gavage and euthanized 24 h after the treatment. Among blood components, maximum radioactivity was found to be associated with red blood cells (RBCs). After 3 doses, there was 112, 79, and 67% increase in the radioactivity in the whole blood, RBCs, and hemolysate, respectively, in comparison to 1 dose. In comparison to RBCs, plasma had only 40 and 16% radioactivity after the administration of 1 and 3 doses, respectively. Spleen homogenate at 1 dose had one-third of the radioactivity in the TCA precipitate, which increased to 40% at 3 doses, while the total radioactivity increased 256% over 1 dose. Liver, which had almost double the radioactivity on a per gram tissue basis compared to the spleen at one dose, did not show any appreciable increase in the radioactivity at three doses. However, radioactivity in the TCA precipitate of liver homogenate increased by 92% after 3 doses. The iron content of the spleen in rats given 3 doses of [14C]aniline increased by 85% compared to the rats given just 1 dose. The iron content of liver did not show any change at three doses. These data thus demonstrate a dose-dependent binding and accumulation of radioactivity in erythrocytes and spleen. These interactions, along with parallel increases in the iron content of the spleen, could be critical in the splenic toxicity of anilines.

Fatty acid anilides: In vivo formation and relevance to toxic oil syndrome

“…Red blood cells are the major site for binding and accumulation of aniline (18,42). Our results on persistence of the 16:0 and 18:1 FAAs in the whole blood as compared to that in liver and pancreas are in agreement with the results of aniline binding with red blood cells.…”

INHALATION TOXICITY OF 4-ETHOXYANILINE (p -PHENETIDINE): CRITICAL ANALYSIS OF RESULTS OF SUBACUTE INHALATION EXPOSURE STUDIES IN RATS

“…This is similar to findings previously reported with other agents causing MetHb (e.g., Nair et al, 1986;Hamm et al, 1984;Khan et al, 1995aKhan et al, , 1995bKhan et al, , 1998aKhan et al, , 1998bKhan et al, , 2000. In the present study, a statistically significant increase in MetHb levels was observed at 86.2 mg/m 3 air, and hematological as well as splenic changes appear to coincide.…”

“…It is beyond the scope of this article to address any aspects of the mechanistic principles of the transformation of p-phenetidine into the active metabolite, the ensuing formation of methemoglobin, and secondary responses occurring in the liver and spleen, which have been reviewed in detail elsewhere (e.g., Kiese, 1974;Khan et al, 1995aKhan et al, , 1995bBus & Popp, 1987;Ferrali et al, 1997).…”

“…Therefore, a comparison of "conventional" and "specialized" procedures was made to identify possible shortcomings in study design and timing of collection of blood relative to the end of exposure. Based on studies with agents known to affect the hematopoietic system, endpoints addressing hematotoxicity focused on changes in the peripheral blood, detailed analysis of bone marrow cells, and hemosiderin deposition in the spleen and liver (Albrecht & Neumann, 1985;Bus & Popp, 1987;Ferrali et al, 1997;Khan et al, 1995aKhan et al, , 1995bNair et al, 1986;Hamm et al, 1984). The study described was conducted in compliance with Good Laboratory Practice (GLP) requirements (OECD, 1983) and European Union (EU) animal welfare regulations (European Community, 1986).…”

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

“…Atherosclerosis is a progressive (and inflammatory ) disease (Altman 2003; Binder et al 2002; Blake and Ridker 2001; Duewell et al 2010; Dwyer et al 2004; Forrester 2002, 2004; Gieseg et al 2009; Grainger 2007; Hansson 2001, 2005; Himmelfarb et al 2002; Kibel et al 2008; Kunsch and Medford 1999; Libby 2002; Libby et al 2002; Madamanchi et al 2005a, b; Mullenix et al 2005; Nigro et al 2006; Packard and Libby 2008; Paoletti et al 2004; Popa et al 2007; Rader and Daugherty 2008; Ridker et alet al 2004; Ross 1999; Schleicher and Friess 2007; Subramanian and Ferrante 2009; Sullivan 2009; Tan and Lip 2008; Tang et al 2009; Taqueti et al 2006; Tedgui and Mallat 2006; van Leuven et al 2008; van Oostrom et al 2004; Willerson and Ridker 2004; Young et al 2002) characterized by the accumulation of both oxidised lipids and various fibrous elements in arteries, often as plaques (Lusis 2000; Stocker and Keaney 2004). Several lines of evidence point to the involvement of iron in these processes:

Both iron and oxidised lipids (de Valk and Marx 1999; Smith et al 1992) are found in atherosclerotic lesions (Altamura and Muckenthaler 2009; Brewer 2007; Chau 2000; Fernandes de Godoy et al 2007; Gajda et al 2008; Halliwell 2009; Horwitz et al 1998; Kazi et al 2008; Lee et al 1998; McRae et al 2009; Rajendran et al 2007; Ramakrishna et al 2003; Roijers et al 2005; Smith et al 1992; Stadler et al 2004; Stanley et al 2006; Stocker and Keaney 2005; Sullivan 2009; Watt et al 2006; Wolff et al 2004; Yuan and Li 2008)

Iron depletion by dietary or other means delays the formation of such lesions...

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