Clinical conundrum: managing iron overload after renal transplantation

2021 ◽  
Vol 14 (2) ◽  
pp. e239568
Author(s):  
Binayak Upadhyay ◽  
Steven D Green ◽  
Nabin Khanal ◽  
Aśok C Antony
Keyword(s):  
Iron Overload ◽  
Haemoglobin Concentration ◽  
Iron Chelation ◽  
Immunosuppressive Drug ◽  
Drug Induced ◽  
Hepatic Iron Overload ◽  
Combined Use ◽  
Mild Anaemia ◽  
Parenteral Iron

Iatrogenic iron overload, which is not uncommon in patients undergoing long-term haemodialysis, arises from a combination of multiple red cell transfusions and parenteral iron infusions that are administered to maintain a haemoglobin concentration of approximately 10 g/dL. Although iron overload due to genetic haemochromatosis is conventionally managed by phlebotomy, patients with haemoglobinopathies and chronic transfusion-induced iron overload are treated with iron-chelation therapy. However, the management of iron overload in our patient who presented with hepatic dysfunction and immunosuppressive drug-induced mild anaemia in the post-renal transplant setting posed unique challenges. We report on the decision-making process used in such a case that led to a successful clinical resolution of hepatic iron overload through the combined use of phlebotomy and erythropoiesis stimulating agents, while avoiding use of iron-chelating agents that could potentially compromise both hepatic and renal function.

Family Perceptions of Barriers and Facilitators of Treatment Protocols for Secondary Stroke Prevention in Children with Sickle Cell Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4805-4805
Author(s):  
Eve S Puffer ◽  
Melanie J Bonner ◽  
Courtney D Thornburg
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Iron Chelation ◽  
Secondary Stroke Prevention ◽  
Treatment Protocols ◽  
History Of ◽  
Family Perceptions

Abstract Abstract 4805 Children with sickle cell anemia (SCA) and a primary overt stroke are at high risk of recurrent (secondary) stroke. Chronic blood transfusion (CBT) dramatically reduces but does not eliminate this high risk, and results in transfusion-related hemosiderosis. We previously reported the use of hydroxyurea/phlebotomy as an alternative to CBT to reduce the risk of secondary stroke and improve management of iron overload (Ware et al. J Pediatr 2004). This study examines the caregiver and child experience with secondary stroke prevention. Individual semi-structured interviews were conducted with primary caregivers and children/adolescents (age > 5 years) recruited from the Duke Pediatric Sickle Cell Program. The interviewer (E.P.) asked about perceptions of risk of recurrent stroke and iron overload with and without therapy and facilitators and barriers of therapy. Interviews were coded and analyzed independently by two investigators (E.P and C.T.). The sample included 14 youth (10 males) with a median age of 12.5 years (range 3–17). All primary caregivers were female. Twelve children had a history of overt stroke and 2 had a history of silent stroke. All children had experience with CBT and 9 were receiving CBT at the time of the interview. Eleven children had experience taking hydroxyurea and 5 were taking hydroxyurea at the time of the interview. All caregivers agreed that their child was at risk of recurrent stroke, identified benefit of current treatment and reported high motivation to adhere to treatment protocols. They noted significant impact that stroke had on school functioning, attention, personality, participation in sports and overall quality of life. Caregiver-reported barriers to CBT and hydroxyurea fell into three main categories: (1) missed work and school and related consequences; (2) unexpected resource-related challenges; and (3) inconvenience of clinic appointments, all of which contributed to burden on the family and sometimes missed clinic appointments and treatments. There were higher levels of concern expressed by caregivers of children on CBT related to the higher frequency and longer length of medical appointments compared with those taking hydroxyurea. The primary child-reported barrier was dislike of needles or shots (although this decreased with age as expected); those taking hydroxyurea also noted that they sometimes forgot to take the medication if they were busy with other activities or fell asleep. Caregiver-reported facilitators of CBT and hydroxyurea included: (1) understanding importance of stroke prevention and connection to consistent treatment; (2) ancillary benefits of treatments in addition to stroke prevention; (3) link between treatment and long-term benefits. Caregivers were able to overcome treatment barriers via the following: (1) logistical supports including appointment and medication reminders; (2) shared responsibility with other family members including the child; (3) trust in medical staff; and (4) faith. Although children disliked needles and shots, many enjoyed the clinic visits due to fun activities in the clinic setting and rewards. In addition, iron overload was a significant concern for caregivers. For those with children on CBT, knowledge of the risks of iron overload motivated adherence with oral iron chelation. Automatic refills facilitated adherence with chelation therapy, but the taste of the medication was a major barrier to adequate iron chelation. Caregivers of children taking hydroxyurea noted the benefit of avoiding iron overload. Of those who had undergone phlebotomy, in-home phlebotomy was noted as a facilitator, though requirement for IV contributed to negative perception. In summary, as clinicians review options for secondary stroke prevention with families, they should discuss family perceptions and individual barriers and facilitators which may impact adherence with therapy and long-term outcome. Future research should also investigate whether these family perceptions predict actual adherence to protocols and treatment outcomes. Disclosures: Off Label Use: Hydroxyurea for secondary stroke prevention in sickle cell disease.

Occurrence of Neoplastic Diseases in a Large Cohort of Thalassemic Patients in Greece

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3264-3264
Author(s):  
Alexandra Kouraklis ◽  
Antonia Chatziliami ◽  
Antonis Kattamis ◽  
Efthimia Vlachaki ◽  
Evangelos Briasoulis ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Cell Lymphoma ◽  
Iron Chelation ◽  
Beta Thalassemia ◽  
Thalassemia Intermedia ◽  
Neoplastic Diseases ◽  
Median Serum ◽  
Neoplastic Disorders

Abstract Abstract 3264 Life expectancy of thalassemic patients, appropriately transfused and adequately iron-chelated, has been substantially extended the last decades. However, these patients are subjected to particular risks which might favor the development of neoplasia, such as transfusional iron overload, high prevalence of viral diseases, particularly HCV infection, and transfusion-associated alteration of their immune status. The occurrence of neoplastic diseases has not been extensively investigated in this patient population. We sought to investigate the occurrence of neoplastic diseases during a 16.5 year-period, in a large cohort of 1972 thalassemic patients (homozygous beta-thalassemia N=1448, thalassemia intermedia N=352 and sickle-cell/beta thalassemia N=172), followed-up in 6 large Greek Thalassemic Units. All documented cases of neoplastic diseases, diagnosed during the period between 1.1.1996 and 30.6.2012 were collected and analyzed. The frequency of each type of neoplasia was then correlated with specific factors, potentially influencing the occurrence of these disorders, and particularly age at first transfusion, frequency of transfusions, previous splenectomy, smoking, use of hydroxyurea, previous autoimmune disorders, presence of HBV, HCV and HIV infection, adequacy of iron chelation and the degree of hepatic siderosis. Totally 38 cases of neoplastic disorders were documented among the 1972 patients. These were Hepatocellular carcinoma (10 cases), non-Hodgkin's Lymphoma (6 cases in total: Marginal-zone lymphoma N=2, Mantle-cell lymphoma N=1, Diffuse large B-cell lymphoma N=1, Burkitt's lymphoma N=1, T-cell lymphoblastic lymphoma N=1), Thyroid carcinoma (3 cases in total: papillary N=2, follicular N=1), Hodgkin's lymphoma (3 cases in total, classical N=2, LPHD N=1), Renal cell cancer (N=3), Colon cancer (N=3), Breast cancer (N=2), Cholangiocarcinoma (N=2), Pre-B Acute Lymphoblastic Leukemia (N=2), Testicular cancer (2 cases in total, seminoma N=1, teratoma N=1), melanoma (N=1), and Renal oncocytoma (N=1). Twenty-eight cases were diagnosed among patients with homozygous beta-thalassemia, 6 among patients with thalassemia intermedia and 4 among patients with sickle-cell/beta thalassemia. Median age at diagnosis of the neoplastic disease was 39 years (age range 21 to 63 years). Twenty-nine cases (76.3%) were diagnosed among previously splenectomized patients, although splenectomy had been performed in 41% of the total cohort of patients. All patients were HIV-negative, 3/31 (9.7%) were HBsAg-positive, whereas 22/37 (59.5%) had HCV infection. Patients were then classified according to the level of liver siderosis and the effectiveness of their iron chelation treatment, estimated by their annual median serum ferritin levels. Eleven patients were found to be adequately chelated (median serum ferritin 310 ng/ml), 16 were moderately-effectively chelated (median serum ferritin 1240 ng/ml) and 11 were inadequately chelated (median serum ferritin 2552 ng/ml). There was no difference in patient's age or in the type of neoplastic disorders occurred in each of the 3 categories, however 3/11 poorly chelated patients were long term survivors, versus 8/16 moderately chelated and 9/11 adequately chelated patients. In conclusion, the prolongation of overall survival of thalassemic patients results in increasing occurrence of neoplastic diseases among this patient population. Splenectomized and HCV-infected patients appear to represent higher-risk groups, whereas the role of iron overload appears not to influence the occurrence of neoplastic diseases but may have an impact on the long-term outcome and clearly deserves further investigation. Disclosures: No relevant conflicts of interest to declare.

Long Term Efficacy, Safety and Tolerability (>24 Months) of Twice Daily Dosing of Deferasirox in Transfusion Dependent Thalassemias Who Were Unresponsive to Standard Once Daily Dose

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 958-958
Author(s):  
Bunchoo Pongtanakul ◽  
Vip Viprakasit
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Once Daily ◽  
Term Efficacy ◽  
Before And After ◽  
Baseline Levels ◽  
Median Change

Background: Clinical efficacy, safety and tolerability of deferasirox (DFX); a once daily oral iron chelator in transfusion dependent thalassemias (TDT) with iron overload can be achieved by appropriate dosage adjustment based on iron burden and ongoing transfusion iron overload. However, even with recommended DFX dosage, at least 40% of our Thai TDT patients did not appropriately respond to DFX. Patients with unresponsiveness to DFX (UR) was defined as (1) having a rising serum ferritin (SF) trend or (2) having a reduction of SF < 30% of baseline levels (BL) at least 3 consecutive mths, with more than two SF measurements >1500 ng/mL; and (3) receiving once daily DFX at an average dosage > 30 mg/kg/day for at least 6 mths. Previously, twice daily dosing (TWD) of DFX was shown to be effective in patients with UR (Pongtanakul B, et al. Blood Cells Mol Dis. 2013) but long term efficacy, safety and tolerability of TWD of DFX is still lacking. Methods: Patients with UR who received TWD of DFX with the same total dose per day > 24 mths were included. CBC, renal function, urine analysis were performed every 3 wks to monitor possible side effect. SF and liver function test were checked every 6 wks. Tolerability and compliance to DFX were evaluated by direct history taking and drug account prescribed. Responsiveness to TWD of DFX (RP) was defined as the patients who showed a decrease of SF or reduction of liver iron concentration (LIC) by MRI > 30% of the BL at 6 or 12 mths. Results: Twenty four TDT patients received TWD of DFX; 4 patients were excluded due to poor compliance and a short follow up period and 4 patients did not meet RP criteria. Sixteen patients were enrolled; 9 male (56%) with a mean (± SD) age of 9.08 ± 3.84 yrs (range 2.1-24.2 yrs). Clinical diagnoses include; Hb E/β thalassemia. (n=12), β thalassemia major (n=3) and Hb Barts hydrops (n=1). Mean follow up time before switching dose were 17.3 ± 7.3 mths. Average SF at BL before DFX and before TWD were 3,039 ± 1,713.7.02 and 3,500 ± 1,403.2 ng/mL, with median % change of SF was +27.58 % (range; -13.4 to +104%). Mean actual DFX dose during 6 mths before switching was 36.3 ± 2.2 mg/kg/day. None had symptoms of gastrointestinal irritation. After TWD, 13 (81.25%) and 16 patients (100%) showed a significant decrease of SF (> 30% of the baseline levels) at 6 and 12 months. Mean SF and median % change of SF at 6 and 12 months after switching were 2,527.56 ± 1,191.80 ng/mL; -29.24 % and 1,695.83 ± 859.16 ng/mL; -53.14%, with statistical significance compared to BL and before switching (p <0.05). Mean transfusion iron load before and after switching were not different (range 0.2-0.4 mg/kg/day). One patient had a SF reduction < 30%, but LIC was significant reduction at 12 months. Nine out of 16 patients were evaluated for LIC; average LIC at BL and at the end of study were reduced from 6.7 to 3.2 mg/g dry wt. None had cardiac T2* < 20 msec. All patients except one tolerated well with DFX at before and after switching (>24 months) with minor adverse events. One patient had severe transaminitis (ALT > 3 times of ULN) but after investigation, this was thought to be result from acute viral hepatitis. This patient could be successfully restarted DFX at the same TWD. Five patients could decrease DFX dosage to < 20 mg/kg/day and switched back to daily dosing (mean dosage was 17.04 mg/kg/day). However, 4 patients, after decreased DFX dosage and switched back to daily dosing; their SF increased and required to increase DFX dosage with TWD to maintain SF. Seven patients continued to receive TWD of DFX with mean dosage was 36.4 mg/kg/day. Mean follow up time after TWD of DFX was 44.1 + 9.8 mths (range 24 - 72 mths). Conclusion: Herein, we show that TWD of DFX effectively reduced iron burden in TDT with iron overload. Safety and tolerability of this dosing are not different from once daily dosing. Most patients could decrease DFX dosage and switched back to once daily dosing when iron burden decreased. However, 25% (4/16) of these patients still required twice daily dosing with higher dosage to maintain optimal body iron levels. Interestingly, 16% (4/24) of our patients who received TWD could not achieve effective iron chelation. This group of patients may represent those who have different pharmacogenetic background that affect directly to efficacy of DFX causing a resistant to iron chelation therapy. This population confirms for improving iron chelation measures by means of a newer iron chelation agent or a combination of DFX with other iron chelation. Disclosures Off Label Use: Twice daily dosing instead of standard daily dosing.

Iron Chelation with Deferasirox (Exjade®) Improves Iron Burden in Patients with Myelodysplastic Syndromes (MDS)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 634-634 ◽  
Author(s):  
Alan F List ◽  
Maria R Baer ◽  
David Steensma ◽  
Azra Raza ◽  
Jason Esposito ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Iron Chelation ◽  
Underlying Disease ◽  
Endocrine Function ◽  
Transfusion Rate ◽  
Open Label ◽  
The Mean ◽  
New Onset

Abstract INTRODUCTION: The majority of patients (pts) with MDS require red blood cell transfusions, which can result in iron overload and its clinical sequelae. The US03 trial is designed to evaluate the long-term efficacy and safety of the once-daily, oral iron chelator, deferasirox (DFX), in pts with lower-risk MDS. In this ongoing study 93/176 pts have now completed 12 months of treatment. METHODS: US03 is a Phase II, open-label, 3-year trial in pts with Low- or Int-1 IPSS-risk MDS and transfusional iron overload (serum ferritin [SF] 1000 μg/L and &gt;20 units RBC transfusions), with serum creatinine (SCr) 2-fold the upper limit of normal (ULN). Initial DFX dose was 20 mg/kg/day and could be increased to 40 mg/kg/day based on tolerability and response. SF was monitored monthly; labile plasma iron (LPI), the reactive species of non-transferrin-bound iron, was assessed quarterly. BASELINE FEATURES: 176 pts were enrolled at 45 centers. Mean age: 70 years (range 21–90); 105 men and 71 women; IPSS Low risk (n=47; 27%); Int-1 (n=126; 72%); other (n=3; 2%). Mean baseline iron status was: SF, 3397 μg/L (863–36,280); LPI, 0.4 μmol/L (0.0–3.6). Forty-one percent of pts had elevated LPI at baseline (≥0.5 μmol/L). Mean number of lifetime prior transfusions: 63; mean duration of transfusions: 3.5 years (0–34). MDS therapy at study entry included azacitidine, hydroxyurea, lenalidomide, thalidomide or decitabine in 25 pts, and growth factors in 48 pts. Calculated creatinine clearance was normal (&gt;80 mL/min) in 77 pts and abnormal (abn) in 99: mildly abn (51– 80 mL/min) in 71; moderately abn (30–50 mL/min) in 25; severely abn (&lt;30 mL/min) in 3. RESULTS: Over 12 months, the mean dose of DFX was 21 mg/kg/day, and the mean transfusion rate was 3.4 units/month. Mean SF±SEM (μg/L) values at baseline, 3, 6, 9 and 12 months were 3397±233 (n=176), 3057±144 (n=143), 2802±128 (n=126), 2635±148 (n=109) and 2501±139 (n=93), respectively. In pts with elevated baseline LPI, sustained suppression of mean LPI to the normal range was achieved after 3 months of treatment. The figures show reductions (±SEM) in SF, and in LPI in pts with baseline LPI ≥0.5 μmol/L. Hematological improvement by IWG 2000 criteria was achieved in 8 pts (5%): erythroid response in 5 (major 3; minor 2); platelet in 1 (major); neutrophil in 1 (major); and combined platelet and neutrophil in 1. SAFETY: Of 173 pts, 18 (10%) discontinued DFX because of suspected adverse events (AEs), and an additional 5 (3%) because of serious AEs (SAEs). The most common AEs were diarrhea (n=9), rash (n=3) and nausea (n=2), while the most common SAEs were rash (n=2) and diarrhea (n=1). Of 147 pts with normal baseline SCr, 26 (18%) increased &gt;ULN on at least two occasions (3.0 mg/dL max SCr). There were 9/172 (5%) and 22/168 (13%) new onset cases of grade 3–4 thrombocytopenia and neutropenia, respectively, none suspected to be related to DFX; 7 and 11 of these pts, respectively, were receiving other MDS treatment therapies, including lenalidomide, decitabine, hydroxyurea and azacitidine. There were 17 deaths (10%), due to sepsis/infection (n=8), disease progression (n=4), intracranial bleed (n=2), cardio-respiratory arrest (n=2) and renal failure (n=1), all thought to be unrelated to DFX. CONCLUSIONS: In these heavily iron-overloaded pts, DFX was generally well tolerated. New onset cytopenias were consistent with the underlying disease. A 2-year extension phase of this study will assess the long-term safety and efficacy of DFX as well as the clinical impact on cardiac, hepatic and endocrine function. Figure Figure

scholarly journals Iron overload in transfusion-dependent patients

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 337-344 ◽  
Author(s):  
Thomas D. Coates
Keyword(s):  
Iron Overload ◽  
Iron Homeostasis ◽  
Prolonged Exposure ◽  
Iron Chelation ◽  
Close Relation ◽  
Therapeutic Strategies ◽  
Clinical Approach ◽  
Iron Loading ◽  
Marrow Activity

Abstract Before the advent of effective iron chelation, death from iron-induced cardiomyopathy occurred in the second decade in patients with transfusion-dependent chronic anemias. The advances in our understanding of iron metabolism; the ability to monitor iron loading in the liver, heart, pancreas and pituitary; and the availability of several effective iron chelators have dramatically improved survival and reduced morbidity from transfusion-related iron overload. Nevertheless, significantly increased survival brings about new complications such as malignant transformation resulting from prolonged exposure to iron, which need to be considered when developing long-term therapeutic strategies. This review discusses the current biology of iron homeostasis and its close relation to marrow activity in patients with transfusion-dependent anemias, and how biology informs clinical approach to treatment.

Evidence for tissue iron overload in long-term hemodialysis patients and the impact of withdrawing parenteral iron

2012 ◽  
Vol 89 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Hussam Ghoti ◽  
Eliezer A. Rachmilewitz ◽  
Ramon Simon-Lopez ◽  
Raed Gaber ◽  
Zeev Katzir ◽  
...  
Keyword(s):  
Iron Overload ◽  
Hemodialysis Patients ◽  
Tissue Iron ◽  
Parenteral Iron ◽  
The Impact

scholarly journals Translational regulation of ferritin synthesis in rat liver. Effects of chronic dietary iron overload

1989 ◽  
Vol 264 (3) ◽  
pp. 925-928 ◽  
Author(s):  
G Cairo ◽  
L Tacchini ◽  
L Schiaffonati ◽  
E Rappocciolo ◽  
E Ventura ◽  
...  
Keyword(s):  
Iron Overload ◽  
Translational Regulation ◽  
Dietary Iron ◽  
Iron Storage ◽  
Subunit Mrna ◽  
Ferritin Synthesis ◽  
Parenteral Iron ◽  
Liver Ferritin ◽  
Ferritin H

In rats with chronic dietary iron overload, a higher amount of liver ferritin L-subunit mRNA was found mainly engaged on polysomes, whereas in control rats ferritin L-subunit mRNA molecules were largely stored in ribonucleoprotein particles. On the other hand, ferritin H-subunit mRNA was unchanged by chronic iron load and remained in the inactive cytoplasmic pool. In agreement with previous reports, in rats acutely treated with parenteral iron, only the ferritin L-subunit mRNA increased in amount, whereas both ferritin subunit mRNAs shifted to polysomes. This may indicate that, whereas in acute iron overload the hepatocyte operates a translation shift of both ferritin mRNAs to confront rapidly the abrupt entry of iron into the cell, during chronic iron overload it responds to the slow iron influx by translating a greater amount of L-subunit mRNA to synthesize isoferritins more suitable for long-term iron storage.

scholarly journals Long-term survival and reversal of iron overload after marrow transplantation in dogs with congenital hemolytic anemia

Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 66-70
Author(s):  
PL Weiden ◽  
RC Hackman ◽  
HJ Deeg ◽  
TC Graham ◽  
ED Thomas ◽  
...  
Keyword(s):  
Iron Overload ◽  
Hemolytic Anemia ◽  
Marrow Transplantation ◽  
Good Health ◽  
Hepatic Iron ◽  
Term Survival ◽  
Essentially Normal ◽  
Hepatic Iron Overload ◽  
Congenital Hemolytic Anemia

Severe hemolytic in Basenji dogs secondary to pyruvate kinase deficiency was corrected by marrow transplantation from hematologically normal littermates. These dogs have now been followed for more than 5.5 yr. Essentially normal hematopoiesis has persisted, and the dogs remain in good health without cirrhosis or osteosclerosis. Furthermore, hepatic iron overload present before transplantation has gradually decreased. These results in dogs suggest that marrow transplantation could prevent the morbidity and mortality of severe hemolytic anemia and associated iron overload in man.

scholarly journals The Effects of Chronic Iron Overload in Rats with Acute Acetaminophen Overdose

2018 ◽  
Vol 46 (5) ◽  
pp. 597-607 ◽  
Author(s):  
Zvi Ackerman ◽  
Galina Skarzinski ◽  
Gabriela Link ◽  
Maya Glazer ◽  
Orit Pappo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
Cell Damage ◽  
Hepatic Cell ◽  
Hepatic Expression ◽  
Iron Administration ◽  
Hepatic Oxidative Stress ◽  
Hepatic Iron Overload ◽  
Sinusoidal Cell ◽  
Parenteral Iron

Background and Aims: Rats are resistant to acetaminophen (APAP) hepatotoxicity. In this study, we evaluated whether by augmentation of the hepatic oxidative stress, through the induction of hepatic iron overload (IO), it will be feasible to overcome the resistance of rats to the toxic effects of APAP. Method: Rats with no or increased hepatic IO. Results: Providing iron by diet induced hepatocellular IO, while parenteral iron administration induced combined hepatocellular and sinusoidal cell IO. APAP administration to rats with no IO caused an increase in hepatic oxidative stress and a decrease in the hepatic antioxidative markers but no hepatic cell damage. APAP administration to rats with hepatocellular IO further amplified the hepatic oxidative stress but induced only hepatocyte feathery degeneration without any increase in serum aminotransaminases. APAP administration to rats with combined hepatocellular and sinusoidal cell IO caused an unexpected decrease in hepatic oxidative stress and increase in the hepatic antioxidative markers and no hepatic cell damage. No hepatic expression of activated c-jun-N-terminal kinase was detected in any of the rats. Conclusions: The hepatic distribution of iron may affect its oxidative/antioxidative milieu. Augmentation of hepatic oxidative stress did not increase the rats’ vulnerability to APAP.

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