Blood cell oxidative stress precedes hemolysis in whole blood–liver slice co-cultures of rat, dog, and human tissues

Vickers, Alison E. M.; Sinclair, John; Fisher, Ron; Morris, Sherri J.; Way, William

doi:10.1016/j.taap.2010.01.017

Cited by 18 publications

(9 citation statements)

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“…It has been reported previously that Fpn expression is upregulated concurrently with Hmox1 expression in response to OS and that this upregulated expression translates to increased protein levels (41). Echoing the upregulation of Hmox1 expression, Fpn mRNA expression also showed significantly higher levels in Atm Ϫ/Ϫ mice than in the wild-type animals on the high-iron diet (P ϭ 0.008; Fig.…”

Section: G557 Iron Loading and Oxidative Stress In The Atmsupporting

confidence: 53%

“…Transition metals such as iron act as pro-oxidative molecules by catalyzing the conversion of weak reactive oxygen species such as H 2 O 2 to produce highly reactive hydroxyl radicals that cause significant oxidative damage (2). Within normally functioning cells, concurrent with the upregulation of Hmox1 in response to OS is the upregulation in expression of the iron exporter Ferroportin (Fpn) (41). In this OS defense system, the upregulation of Fpn expression leads to increased ferroportin protein at the cell surface, providing increased export of the potentially harmful iron from the cells, leaving the antioxidants to act in cellular defense.…”

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confidence: 99%

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Iron loading and oxidative stress in theAtm^−/−mouse liver

McDonald

Ostini

Wallace

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Section: G557 Iron Loading and Oxidative Stress In The Atmsupporting

confidence: 53%

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confidence: 99%

Iron loading and oxidative stress in theAtm^−/−mouse liver

McDonald

Ostini

Wallace

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Indeed studies have shown that oxidative stress precedes hemolysis of the red blood cells (Jeney et al, 2002;Jollow and McMillan, 2001) following a similar mechanism in both human and rats when exposed to highly oxidative compounds (Vickers et al, 2010). Shortened survival and removal of pitted erythrocytes explains only part of hemolysis in presence of malaria infection (Arguin, 2014;Jauréguiberry et al, 2014;Kurth et al, 2016;Rolling et al, 2015), unparasitized red blood cells are also cleared (Newton et al, 2001).…”

Section: Discussionmentioning

confidence: 98%

Artemisinin-induced delayed hemolysis after administration of artesunate and artesunate-amodiaquine in malaria-free Wistar rats

et al. 2017

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Background: Hemolysis is common in malaria infection and during the course of treatment. Previous studies have reported delayed post-artemisinin hemolysis occurring in naïve and immune individuals treated with parenteral or oral artemisinin-derivatives. This study aims to understand if delayed hemolysis occurs in the absence of malaria parasites and the underlying mechanisms for the hemolytic effects after administration of two antimalarial drugs to malaria-free Wistar rats. Methods: Forty animals were randomized into 5 groups of eight animals each; they received 4 mg/kg artesunate for 7 days (AS), 4 mg/kg artesunate plus 10mg/kg amodiaquine for 3 days (ASQ), 10mg/kg amodiaquine for 3 days (AQ), distilled water [normal control], (Control) and 1mg/kg phenylhydrazine for 1 day to induce hemolysis (PHZ) groups respectively. Packed cell volume (PCV), white blood cell differential count and serum haptoglobin (Hpt) levels were determined in all groups on day 4 and 18 to detect hemolysis. Mean values were compared using t-test and ANOVA with p values <0.05 taken to be significantly different. Results: Post-treatment mean PCV on day 4 was significantly lower than day 18 in all groups except AS group which had similar PCV all through evaluation. Although AQ had lowest mean PCV on day 4, by day 18, mean PCV returned to normal and hpt levels was significantly higher than AS and ASQ groups (p<0.001). Hpt level (mean ± sem) for AS, ASQ, AQ, and control on day 18 were: 18.67 ± 0.004, 50.66 ± 0.014, 73.06 ± 0.003, and 74.13 ± 0.032 mg/dl respectively (p < 0.0001). On day 18, AS and ASQ had significantly lower Hpt level compared to day 4 (p <0.001). No neutropenia was observed during the study. Conclusion: Artesunate induces delayed hemolysis in malaria-free animals possibly through an oxidative toxic effect on the red blood cell membrane. Delayed post-treatment hemolysis was not observed with artesunateamodiaquine or amodiaquine alone.

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“…In the presence of drug-induced injury, the tissue response may include aspects of inflammation, repair and regeneration with the outcome determined by the extent of injury and number of hits [23,24]. Human liver slices cultured for several days exhibit the activation of endothelial cells, Kupffer cells, stellate cells and repair pathways [25,26]. Advancements in the culturing of human liver slices to extend the viability of human liver slices to several days has contributed to the evaluation of time-dependent changes, likely due to the formation of minor metabolites and the manifestations of the consequences [8,26,27].…”

Section: Introductionmentioning

confidence: 99%

Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

Vickers¹,

Ulyanov

Fisher³

2017

IJMS

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Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM), diclofenac (DCF, 1 mM) and etomoxir (ETM, 100 µM). Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 µM) and cyclosporin A (CSA, 10 µM), while GSH was affected more than ATP by methimazole (MMI, 500 µM), terbinafine (TBF, 100 µM), and carbamazepine (CBZ 100 µM). Oxidative stress genes were affected by TBF (18%), CBZ, APAP, and ETM (12%-11%), and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%-6%). Apoptosis genes were affected by DCF (14%), while apoptosis plus necrosis were altered by APAP and ETM (15%). Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%), ETM (66%), DCF, TBF, MMI (61%-60%), APAP, CBZ (57%-56%), and DTL (48%). Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%), CBZ and ETM (44%-43%), APAP and DCF (40%-38%), MMI, TBF and CSA (37%-35%). This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

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Blood cell oxidative stress precedes hemolysis in whole blood–liver slice co-cultures of rat, dog, and human tissues

Cited by 18 publications

References 59 publications

Iron loading and oxidative stress in theAtm^−/−mouse liver

Iron loading and oxidative stress in theAtm^−/−mouse liver

Artemisinin-induced delayed hemolysis after administration of artesunate and artesunate-amodiaquine in malaria-free Wistar rats

Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

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Blood cell oxidative stress precedes hemolysis in whole blood–liver slice co-cultures of rat, dog, and human tissues

Cited by 18 publications

References 59 publications

Iron loading and oxidative stress in theAtm−/−mouse liver

Iron loading and oxidative stress in theAtm−/−mouse liver

Artemisinin-induced delayed hemolysis after administration of artesunate and artesunate-amodiaquine in malaria-free Wistar rats

Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

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Product

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Iron loading and oxidative stress in theAtm^−/−mouse liver

Iron loading and oxidative stress in theAtm^−/−mouse liver