Bilateral ocular deposit of chlorpromazine / Depósito ocular bilateral de clorpromazina

ABSTRACT Chlorpromazine is a medication widely used in psychiatry for the treatment of psychoses, especially schizophrenia. Since 1964, published articles have been correlating this medication with the appearance of ocular alterations. In this paper, we report the case of a 65-year-old patient with ocular effects due to long-term therapy with chlorpromazine. Biomicroscopy of both eyes presented diffuse granular brown deposits, most prominent at the deep stroma and corneal endothelium level. Also showed anterior subcapsular brown deposits with a stellate pattern in the lens. The total amount exceeds 2.000g (significant for the ocular alterations described) considering the patient's daily dosage of chlorpromazine of 300mg for ten years. After performing complete ophthalmic evaluation and discarding other causes for the ocular deposits, we diagnosed a secondary corneal deposit and cataract due to the use of chlorpromazine. This case reinforces the importance of periodic follow-up with an ophthalmologist for chlorpromazine users to trace ocular changes, heeding the exposure time and its dosage.

RESUMO A clorpromazina é uma medicação muito empregada na psiquiatria para tratamento de psicoses, especialmente em casos de esquizofrenia. Desde 1964 existem artigos publicados que correlacionam o uso dessa medicação com o aparecimento de alterações oculares. Neste trabalho, relatamos o caso de um paciente de 65 anos com efeitos oculares devido à terapia de longo prazo com clorpromazina. A biomicroscopia de ambos os olhos apresentou depósitos granulares difusos e de cor marrom, mais proeminente ao nível do estroma profundo e do endotélio da córnea, além de depósitos castanhos subcapsulares anteriores centrais em um padrão estrelado no cristalino. Considerando a dose diária de clorpromazina de 300mg por 10 anos usada pelo paciente, a quantidade total ultrapassa 2.000g (dose considerada significativa para as alterações oculares descritas). Após avaliação oftalmológica completa e descartado outras causas desses depósitos oculares, foram diagnosticados depósito corneano e catarata secundários ao uso de clorpromazina. O caso apresentado reforça a importância do acompanhamento oftalmolÓgico periÓdico de usuários de clorpromazina para o rastreio de alteraçÕes oculares, atentando-se ao tempo de exposição à droga e à posologia da mesma.

A prospective, randomized, double-blind trial of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department.

OBJECTIVE: To compare the efficacy of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department (ED). BACKGROUND: Migraine is a common, incapacitating neurological condition. Although chlorpromazine and prochlorperazine are known to be safe, efficacious treatments for migraine, they have never been directly compared. DESIGN: We performed a prospective, randomized, double-blind clinical trial at a tertiary hospital in Melbourne, Australia. Adults aged 18-65 years, who presented with migraine, were eligible for recruitment. Sixty-six patients were randomized to either chlorpromazine 12.5 mg or prochlorperazine 12.5 mg, both infused in 500 ml of sodium chloride 0.9% over 30 min. Headache severity score, nausea severity score, and the presence of photophobia and phonophobia were assessed at 0, 30, 60, and 120 min. Adverse effects and the need for rescue therapy were recorded. The primary outcome was a reduction in headache severity score from baseline at 60 min post-commencement of the study medicine infusion. RESULTS: Sixty-five patients were included in the analysis. There was a median reduction in headache severity score at 60 min of 3.0 (interquartile range 1.0-4.0) in the chlorpromazine arm versus 2.0 (1.0-4.0) in the prochlorperazine arm (median difference -0.5 (95% confidence interval, -1.9 to 0.9)). We saw no evidence of a difference in secondary outcomes at 30, 60, or 120 min. Side effects were reported in 16/32 (50%) patients in the chlorpromazine group versus 7/33 (21%) in the prochlorperazine group (p = 0.020). Rescue therapy was required in 7/32 (22%) patients in the chlorpromazine group versus 12/33 (36%) in the prochlorperazine group (p = 0.277). CONCLUSIONS: Both chlorpromazine and prochlorperazine are efficacious treatments for acute migraine in adult patients presenting to the ED. This trial found no evidence of superiority of either agent over the other. Caution should be used when prescribing these medicines in the borderline hypotensive patient; in that circumstance, prochlorperazine should be preferentially used.

Chlorpromazine and promethazine reduces Brain injury through RIP1-RIP3 regulated activation of NLRP3 inflammasome following ischemic stroke.

Objectives: Stroke is an important cause of death and disability. Recent evidence suggests that post-stroke inflammation is an important factor in stroke pathology and a root cause of its lasting consequences. Phenothiazine drugs, like chlorpromazine and promethazine (C + P), induce hypothermia and have been shown to play a major role in neuroprotection. In the present study, we investigated this neuroprotective mechanism by assessing the anti-inflammatory effect of these drugs.Methods: Adult Sprague-Dawley rats underwent 2 h of middle cerebral artery occlusion (MCAO) followed by 6 or 24 h of reperfusion, with or without C + P (8 mg/kg). Infarct volumes, neurological deficits, along with mRNA and protein quantities of receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), NLRPyrin domain containing 3 (NLRP3), and interleukin-1ß (IL-1ß) were assessed, as well as the infiltration of neutrophils and macrophages.Results: C + P induced hypothermia that significantly reduced RIP1, RIP3, NLRP3 and IL-1ß expression, infarction, and immune cell infiltration, while C + P treatment with temperature control at 37°C induced lesser effect.Conclusion: These findings suggest that the anti-inflammatory effect of C + P may be dependent on drug-induced hypothermia and regulation of the NLRP3 inflammasome via the RIP1/RIP3 complex. Future investigations are needed regarding C + P as potential treatment of ischemic stroke.

Intravenous Chlorpromazine as Potentially Useful Treatment for Chronic Headache Disorders.

OBJECTIVE: The aim of this study was to describe a group of patients with chronic headache disorders (CH) and medication overuse headache (MOH) treated with intravenous chlorpromazine (IVC). We hypothesized that IVC is an effective and safe addition to well-known treatment strategies for CH and MOH management. INTRODUCTION: Up to 4% of the general population could experience CH. Most cases occur in women, in association with MOH. To date, evidence to support different treatment strategies is lacking. Although IVC is frequently used in the emergency room (ER), documentation on its use as supportive treatment for CH and for withdrawal management of MOH is poor. METHODS: A retrospective cohort of patients hospitalized to receive treatment for CH in a specialized neurological center in Argentina was analyzed. RESULTS: A total of 35 CH patients were included. Of the 35 patients, 33 (94%) patients also presented MOH. Patients reported only minor side effects to IVC administration (mainly drowsiness and symptomatic hypotension). Three months after inpatient treatment, the number of ER visits made by these patients decreased from an average of 2.8 in the 3 months prior to hospitalization to 0.7 after it (72%, P = .009). Headache frequency decreased in 20/34 (59%) patients during the same time period. Pain levels had dropped from a mean of 8 points at admission (in the scale of 1-10) to 2 points at discharge. In the first 3 months of follow-up, the average number of days per month in which patients experienced headache decreased from 28.9 to 15.4 days (53.3%, P < .0001). CONCLUSION: In this particular group of inpatients, there were no significant safety issues with IVC administration and the study might suggest that the efficacy of IVC as an add-on treatment for CH and MOH.

Retrobulbar chlorpromazine injection in a child with gliosarcoma invasion into the orbits.

This paper has two main purposes: (1) to report a rare case of paediatric gliosarcoma that invaded the surrounding orbit and (2) to demonstrate chlorpromazine injection as a potential treatment option for blind, painful eye caused by tumour invasion. A 12-year-old man who presented with headaches was found to have glioblastoma multiforme and it was excised and treated with radiation and chemotherapy. Seven months later, the tumour recurred as gliosarcoma, a rare variant of glioblastoma multiforme containing distinct gliomatous and sarcomatous components. In spite of treatment, the tumour progressed and eventually invaded into the right orbit. He subsequently developed a proptotic, blind, painful eye and was treated with retrobulbar chlorpromazine injection, which provided immediate symptomatic relief.

Cyclodextrin complexation studies as the first step for repurposing of chlorpromazine.

The antipsychotic drug chlorpromazine (CPZ) has potential for the treatment of acute myeloid leukemia, if central nervous system side-effects resulting from its passage through the blood-brain barrier can be prevented. A robust drug delivery system for repurposed CPZ would be drug-in-cyclodextrin-in-liposome that would redirect the drug away from the brain while avoiding premature release in the circulation. As a first step, CPZ complexation with cyclodextrin (CD) has been studied. The stoichiometry, binding constant, enthalpy, and entropy of complex formation between CPZ and a panel of CDs was investigated by isothermal titration calorimetry (ITC). All the tested CDs were able to include CPZ, in the form of 1:1, 1:2 or a mixture of 1:1 and 1:2 complexes. In particular, a substituted γ-CD, sugammadex (the octasodium salt of octakis(6-deoxy-6-S-(2-carboxyethyl)-6-thio)cyclomaltooctaose), formed exclusively 1:2 complexes with an extremely high association constant of 6.37 × 109 M-2. Complexes were further characterized by heat capacity changes, one- and two-dimensional (ROESY) nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations. Finally, protection of CPZ against photodegradation by CDs was assessed. This was accelerated rather than reduced by complexation with CD. Altogether these results provide a molecular basis for the use of CD in delayed release formulations for CPZ.

Acepromazine and Chlorpromazine as Pharmaceutical-grade Alternatives to Chlorprothixene for Pupillary Light Reflex Imaging in Mice.

Studies of visual responses in isoflurane-anesthetized mice often use the sedative chlorprothixene to decrease the amount of isoflurane used because excessive isoflurane could adversely affect light-evoked responses. However, data are not available to justify the use of this nonpharmaceutical-grade chemical. The current study tested whether pharmaceutical-grade sedatives would be appropriate alternatives for imaging pupillary light reflexes. Male 15-wk-old mice were injected intraperitoneally with 1 mg/kg chlorprothixene, 5 mg/kg acepromazine, 10 mg/kg chlorpromazine, or saline. After anesthetic induction, anesthesia maintenance used 0.5% and 1% isoflurane for sedative- and saline-injected mice, respectively. A photostimulus (16.0 log photons cm-2 s-1; 470 nm) was presented to the right eye for 20 min, during which the left eye was imaged for consensual pupillary constriction and involuntary pupil drift. Time to immobilization, loss of righting reflex, physiologic parameters, gain of righting reflex, and degree of recovery were assessed also. The sedative groups were statistically indistinguishable for all measures. By contrast, pupillary drift occurred far more often in saline-treated mice than in the sedative groups. Furthermore, saline-treated mice took longer to reach maximal pupil constriction than all sedative groups and had lower heart rates compared with chlorpromazine- and chlorprothixene-sedated mice. Full recovery (as defined by purposeful movement, response to tactile stimuli, and full alertness) was not regularly achieved in any sedative group. In conclusion, at the doses tested, acepromazine and chlorpromazine are suitable pharmaceutical-grade alternatives to chlorprothixene for pupil imaging and conceivably other in vivo photoresponse measurements; however, given the lack of full recovery, lower dosages should be investigated further for use in survival procedures.

Light and electron microscopy of chlorpromazine-induced hyperpigmentation.

Chlorpromazine may induce abnormal skin hyperpigmentation in exposed areas, described as slate-gray, purple, or blue-grayish discoloration. A 58-year-old man with schizophrenia, had been taking chlorpromazine for 5 years, and his sun-exposed skin areas exhibited a blue-grayish color. Large deposits of brown pigment and granular basophilic material were seen in the dermis with light microscopy. HMB-45 and anti-Melan-A antibody immunostaining labeled some pigment in the dermis. Transmission electron microscopy identified deposits among dermal collagen bundles collagen in both transverse and longitudinal sections. In the latter, an arboriform aspect of deposits was quite clear, and some melanophages were also seen. The three-dimensional examination of the dermis with scanning electron microscopy also identified deposits, which at higher magnification demonstrated an appearance in the shape of leaves, grass-like, interspersed with normal collagen. These results suggest a complex pathogenic mechanism, including deposition of dermal melanin together with drug itself and potentially additional unknown metabolites.

Safety and Effectiveness of Intravenous Chlorpromazine for Agitation in Critically Ill Patients.

BACKGROUND: Agitation is common in the intensive care unit (ICU). Although antipsychotics are frequently used as first-line therapy, chlorpromazine has fallen out of favor due to risk of cardiovascular complications and severe hypotension. Although chlorpromazine is used anecdotally, there is a lack of data regarding its safety and effectiveness. The objective of this study was to investigate the use of intravenous (IV) chlorpromazine for agitation in the ICU setting. METHODS: A retrospective review was performed at a tertiary care academic medical center. Patients were included if they received IV chlorpromazine in the ICU for agitation, infused at a rate of 1 mg/min. Primary end points were change in systolic blood pressure (SBP), heart rate (HR), and mean arterial pressure (MAP) within 4 hours of administration. Secondary end points included change in vasopressor and adjunct sedative medication requirements, achievement of Richmond-Agitation Sedation Scale (RASS) 0 to -1, and incidence of cardiac arrhythmias. RESULTS: A total of 39 patients encompassing 107 IV chlorpromazine administrations were included. The median dose was 25 mg. Median vital signs prior to infusion were SBP 129 mm Hg, HR 90 beats/minute, and MAP 88 mm Hg. Over the subsequent 4 hours, SBP and HR did not change significantly (P = .83 and P = .10, respectively). Mean arterial pressure decreased from a median of 88 to 83 mm Hg (P = .04). There were no significant changes in vasopressor requirements, adjunct sedative medication requirements, or achievement of RASS goal. No patients developed symptomatic cardiac arrhythmias. CONCLUSION: In our small retrospective study, the use of IV chlorpromazine at routine doses did not result in clinically significant hemodynamic changes when infused at a rate of 1 mg/min. Intravenous chlorpromazine may be considered as a potential treatment option for agitation in ICU patients with appropriate monitoring.

Chlorpromazine-impregnated catheters as a potential strategy to control biofilm-associated urinary tract infections.

Aim: This study proposes the impregnation of Foley catheters with chlorpromazine (CPZ) to control biofilm formation by Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae. Materials & methods: The minimum inhibitory concentrations (MICs) for CPZ and the effect of CPZ on biofilm formation were assessed. Afterward, biofilm formation and the effect of ciprofloxacin and meropenem (at MIC) on mature biofilms grown on CPZ-impregnated catheters were evaluated. Results: CPZ MIC range was 39.06-625 mg/l. CPZ significantly reduced (p < 0.05) biofilm formation in vitro and on impregnated catheters. In addition, CPZ-impregnation potentiated the antibiofilm activity of ciprofloxacin and meropenem. Conclusion: These findings bring perspectives for the use of CPZ as an adjuvant for preventing and treating catheter-associated urinary tract infections.

Adverse drug reactions experienced by out-patients taking chlorpromazine or haloperidol at Zomba Mental Hospital, Malawi.

OBJECTIVE: Drugs for managing mental disorders can cause adverse drug reactions (ADRs) that have negative impacts on patients yet, in Malawi, epidemiological data on the drug-related problems are limited. This study assessed the prevalence and severity of ADRs in out-patients at Zomba Mental Hospital. RESULTS: Twenty-six of forty patients (65.0%) were taking haloperidol and 14 (35.0%) chlorpromazine. The commonest diagnosis was schizophrenia (n = 23, 57.5%) followed by epileptic psychosis (n = 4, 10.0%) and general psychosis (n = 4, 10.0%) with one of psychotic depression and one psychosis secondary to general medical condition. Comorbidities were also found with epilepsy being the commonest (n = 4, 10.0%). All patients reported at least one ADR of varying severity (mild, moderate and severe). Polydipsia was the most prevalent (24, 60.0%) followed by weight gain (20, 50.0%), spasm (15, 37.5%) and xerostomia (15, 37.5%). Some ADRs were gender specific and these included impotence (6/27, 29.6%) for males and menstrual changes (3/14, 21.4%) for females. Severe ADRs were more common in the older aged group (> 35 years 8.3% vs 7.1%), in males (11.1% vs 0.0%) and on chlorpromazine (14.3% vs 3.8%). Patients taking chlorpromazine and haloperidol are at risk of experiencing a wide range of ADRs with varying degrees of severity.

Polymorphic assembly of virus-capsid proteins around DNA and the cellular uptake of the resulting particles.

Virus-like particles (VLPs), i.e. molecular assemblies that resemble the geometry and organization of viruses, are promising platforms for therapeutics and imaging. Understanding the assembly and cellular uptake pathways of VLPs can contribute to the development of new antiviral drugs and new virus-based materials for the delivery of drugs or nucleic acid-based therapies. Here we report the assembly of capsid proteins of the cowpea chlorotic mottle virus (CCMV) around DNA into defined structures at neutral pH. Depending on the type of DNA used, we are able to create spherical structures of various diameters and rods of various lengths. In order to determine the shape dependency, the cellular uptake routes and intracellular positioning of these formed polymorphic VLPs in RAW264.7, HeLa and HEK 293 cells are evaluated using flow cytometry analysis with specific chemical inhibitors for different uptake routes. We observed particular uptake routes for the various CCMV-based nanostructures, but the experiments point to clathrin-mediated endocytosis as the major route for cell entry for the studied VLPs. Confocal microscopy reveals that the formed VLPs enter the cells, with clear colocalization in the endosomes. The obtained results provide insight in the cargo dependent VLP morphology and increase the understanding of shape dependent uptake into cells, which is relevant in the design of new virus-based structures with applications in drug and gene delivery.

Low dose concomitant treatment with chlorpromazine and promethazine is safe in acute ischemic stroke.

BACKGROUND: Acute ischemic stroke (AIS) is associated with significant morbidity and mortality and has a very narrow window of treatment with fibrinolytics. We investigated the safety and efficacy of combined chlorpromazine and promethazine (C+P) treatment in AIS. METHODS: A total of 64 consecutive patients diagnosed with AIS were selected and were randomly (double-blind) assigned into either the control group (standard of care [SOC] treatment) or the treatment group (SOC+C+P [12.5+12.5 mg BID or 25+25 mg BID]) which were treated for 2 weeks. The National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) were computed prior to and after treatment to evaluate neurological deficits and daily functional status. RESULTS: In our study, 64 patients (males=81.3%) were divided into either the control (34 patients, 83.3% males, mean age=58.8±11.7 years) or the study group (30 patients, 79.4% males, mean age=62.3±9.1 years). While the NIHSS scores were not different between the control and treatment group at admission (P>0.05), a greater proportion of the cohort in both the groups (control group low NIHSS=79.4%, high NIHSS=20.6%, P<0.01) had a lower NIHSS at admission and (treatment group low NIHSS=83.3%, high NIHSS=16.7%, P<0.01). Interestingly, while both the control and treatment group had lower NIHSS and mRS scores at 90d post treatment compared to those at baseline, there were no significant differences in those scores between the two group (P>0.05) suggesting no improved benefit with C+P. Moreover, using C+P did not lead to any serious adverse effects when compared to the treatment group. CONCLUSIONS: While the addition of low dose chlorpromazine and promethazine to standard of care for acute ischemic stroke did not have any significant improvement in functional outcomes, there were no serious adverse effects. Thus, the use of chlorpromazine and promethazine in the acute ischemic stroke setting and future studies using higher doses of C+P are justified.

Effectiveness of intravenous dexamethasone, metoclopramide, ketorolac, and chlorpromazine for pain relief and prevention of recurrence in the migraine headache: a prospective double-blind randomized clinical trial.

Dexamethasone, metoclopramide, ketorolac, and chlorpromazine have been used for the treatment of migraine headache. However, the effectiveness of these drugs in pain relief and prevention of recurrence and their side effects have not been compared yet. This was a randomized, double-blind clinical trial. Subjects were randomized to four groups; each received one of the following drugs intravenously: dexamethasone 8 mg, ketorolac 30 mg, metoclopramide 10 mg, and chlorpromazine 25 mg. The severity of headache in the two groups was assessed at starting point, 1 h and 24 h after the administration of drug using the visual analogue scale (VAS) on a scale of 0 to 10. No significant difference was found in the severity of symptoms between the four study groups before treatment, 1 h, and 24 h after treatment. The effect of all mentioned drugs on acute migraine headache was statistically significant at 1 and 24 h post-treatment compared to baseline. No significant difference was detected in the number of unresponsive cases between the four groups. There was a trend toward higher effectiveness of dexamethasone in prevention of recurrence (P = 0.05). Side effects were more common in chlorpromazine and less common in the dexamethasone-treated patients (P < 0.001). The present clinical trial shows the effectiveness of dexamethasone in prevention of recurrence and low frequency of treatment side effects.

Intravenous Chlorpromazine for the Short-Term Treatment of Insomnia in End-Stage Cancer Patients With Difficulty in Oral Administration.

The objective of the study was to evaluate effectiveness and safety of intravenous chlorpromazine for the short-term treatment of insomnia in end-stage cancer patients. Insomnia occurs as one of distressing symptoms in 70% of end-stage cancer patients. End-stage cancer patients often have difficulty in oral administration because of disease progress. We retrospectively evaluated 30 end-stage cancer patients with difficulty in oral administration who received intravenous chlorpromazine for the short-term treatment of insomnia. A primary end point was sleep quality based on St. Mary's Hospital Sleep Questionnaire 3 days after the treatment. Improved sleep quality was observed on the day after the treatment and later (P < .001), and the effective rate mean was 0.63 (95% confidential interval: 0.45-0.81) 3 days after the treatment. Increased total sleep time and decreased sleep latency time were observed 3 days after the treatment (P < .001); however, no improvement in depth of sleep was achieved (P = .231). There was no adverse event except for two delirium cases. The study indicated that intravenous chlorpromazine can be applied safely and effectively for the short-term treatment of insomnia in end-stage cancer patients with difficulty in oral administration.

Factors Associated with the Effectiveness of Intravenous Administration of Chlorpromazine for Delirium in Patients with Terminal Cancer.

BACKGROUND: Delirium in patients with terminal cancer is irreversible and increases treatment resistance, which leads to a deterioration in quality of life. OBJECTIVE: To investigate factors affecting the effectiveness and safety of intravenous chlorpromazine for irreversible delirium in patients with terminal cancer. DESIGN/MEASUREMENTS: Multiple regression analysis for factors affecting treatment effectiveness was carried out based on a retrospective comparison between responders and nonresponders to intravenous chlorpromazine. SETTING/SUBJECTS: Ninety-seven patients with terminal cancer who were treated with intravenous chlorpromazine for irreversible delirium were included. RESULTS: The rate of patients with ≥50% improvement in mean Nursing Delirium Screening Scale score from pretreatment to day three of chlorpromazine treatment was 0.48 (95% confidence interval [CI]: 0.38-0.58). Factors affecting chlorpromazine treatment effectiveness were hyperactive delirium (odds ratio [OR]: 6.25, 95% CI: 1.14-34.5) and longer survival (OR: 1.096, 95% CI: 1.05-1.14). The mean chlorpromazine dose was low, at 17.9 mg/day. Adverse events were reported in 11 patients (11.3%) by day three of chlorpromazine treatment, and all were observed in patients who survived less than two weeks after chlorpromazine treatment. Patients who died, who had decreased blood pressure during chlorpromazine administration, and who showed acute akathisia all displayed shock index ≥1. CONCLUSIONS: Intravenous administration of low-dose chlorpromazine may be an effective and safe treatment option for delirium in patients with terminal cancer who have hyperactive delirium, longer predictive prognosis, and shock index <1.

Iron overload prevents oxidative damage to rat brain after chlorpromazine administration.

The hypothesis tested is that Fe administration leads to a response in rat brain modulating the effects of later oxidative challenges such as chlorpromazine (CPZ) administration. Either a single dose (acute Fe overload) or 6 doses every second day (sub-chronic Fe overload) of 500 or 50 mg Fe-dextran/kg, respectively, were injected intraperitoneally (ip) to rats. A single dose of 10 mg CPZ/kg was injected ip 8 h after Fe treatment. DNA integrity was evaluated by quantitative PCR, lipid radical (LR·) generation rate by electron paramagnetic resonance (EPR), and catalase (CAT) activity by UV spectrophotometry in isolated brains. The maximum increase in total Fe brain was detected after 6 or 2 h in the acute and sub-chronic Fe overload model, respectively. Mitochondrial and nuclear DNA integrity decreased after acute Fe overload at the time of maximal Fe content; the decrease in DNA integrity was lower after sub-chronic than after acute Fe overload. CPZ administration increased LR· generation rate in control rat brain after 1 and 2 h; however, CPZ administration after acute or sub-chronic Fe overload did not affect LR· generation rate. CPZ treatment did not affect CAT activity after 1-4 h neither in control rats nor in acute Fe-overloaded rats. However, CPZ administration to rats treated sub-chronically with Fe showed increased brain CAT activity after 2 or 4 h, as compared to control values. Fe supplementation prevented brain damage in both acute and sub-chronic models of Fe overload by selectively activating antioxidant pathways.