Profile of oxidative stress in response to treatment for type 1 leprosy reaction.

OBJECTIVE: To measure oxidative stress in Type 1 leprosy reaction, and to document the effect of anti-leprosy multidrug therapy (MDT) and anti-reaction drugs on measures of oxidative stress. MATERIALS AND METHODS: A prospective study was carried out at a teaching hospital involving consecutive patients with Type 1 reaction. MDA (malondialdehyde), FRAP (ferric reducing ability of plasma) and GSH (reduced glutathione) were measured in venous blood samples as measures of oxidative stress and compared at inclusion, after 4 weeks of initial therapy (following standard guidelines including MDT, NSAIDS, and systemic steroids), and 4 weeks after clinical remission. RESULTS: The final study cohort included 40 patients with Type 1 reaction (different treatment arms) after excluding for confounding factors such as prior treatment, smoking, NSAID use or concurrent illness requiring therapy. Measures of lipid derived oxidative stress assessed by MDA showed a significant rise with 4 weeks of therapy and a trend towards decline after clinical resolution. In contrast, the other two measures of anti-oxidants namely GSH and FRAP, showed a significant decrease (P < 0.05) at 4 weeks of treatment followed by a significant increase after 4 weeks of clinical remission of reaction. CONCLUSION: MDT and anti-reactional treatment is associated with significant increases in FRAP and GSH levels, reflecting a reduction in the oxidative stress in patients treated for Type 1 reaction. However, lipid peroxidation as measured by MDA is only partially controlled with treatment.

Status of free radicals and antioxidants in leprosy patients.

Oxidative stress is a condition associated with an increased rate of cellular damage induced by the oxygen derived oxidants commonly known as reactive oxygen species (ROS). ROS are capable of damaging cellular constituents generated in excess during the chronic, inflammatory, neurodegenerative disease process of leprosy. Severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. The decreased levels of SOD, glutathione and total antioxidant status in leprosy patients may indicate a degradation of these antioxidant enzymes by free radicals during detoxification processes. The subjects for this study comprises of Normal human volunteers (NHV, n = 20) and treated MB patients (MB, n = 20). The levels of lipid peroxidation products are increased in MB Patients (*P < 0.001). SOD (**P < 0.0001) and glutathione levels (***P < 0.0001) decreased in MB Patients in comparision with normal human volunteers. The present study of estimation of antioxidants conclude that the free radical activity was increased and the total antioxidant status was decreased in all MB patients, indicating that there was an oxidative stress even after the treatment with MDT. The decreased levels of SOD, glutathione indicate a link between oxidative stress and leprosy. Since the MB patients are unable to produce sufficient amount of antioxidant to cope up with the increased oxidative stress in them. Providing nutritional supplementation may present a novel approach for fast recovery. Administration of exogenous antioxidants like vitamin C, tocopherols would prevent tissue damage and make the patient therapeutically benefited.

Oxidative stress and leukocyte migration inhibition response in cutaneous adverse drug reactions.

BACKGROUND: Cutaneous adverse drug reactions (CADRs) may either be immunological or non-immunological. The precise mechanisms, however, are largely obscure. Other concomitant mechanisms may amplify and/or contribute to the severity and duration of a reaction. One such mechanism could be oxidative stress, a state of imbalance between reactive oxygen species, and their subsequent detoxification by antioxidants. AIMS: (a) to assess the oxidative stress status in the blood of cutaneous drug reaction patients by assaying for reduced glutathione (GSH) and malondialdehyde (MDA) levels, (b) to determine the leukocyte migration inhibition (LMI) response in these patients in response to the suspected drug (s), and (c) to look for the association between oxidative stress parameters and LMI. METHODS: Ethical committee approval was obtained for this study. Fresh venous blood samples were obtained from the patients of CADRs (group A) during the acute phase of reaction and healthy control subjects (group B). MDA levels, a measure of oxidative lipid damage, and reduced GSH levels, a measure of anti-oxidant capacity, were assayed in the blood samples of both groups using spectrophotometry. LMI response was measured by challenging the patients' peripheral blood mononuclear cells with the suspected drug to confirm immunological perturbation. RESULTS: Totally 66 participants, 33 cases in group A and equal number of controls in group B, were studied. The mean MDA levels were found to be raised (P < 0.001), but GSH levels were significantly reduced in group A when compared with group B (P = <0.001). LMI response against drug(s) was performed in 33 cases (group A), out of which 25 cases showed a positive LMI response as follows: fixed drug eruption (10/25), SJS (5/25), urticaria (3/25), exfoliative dermatitis (2/25), morbilliform rash (2/25), erythroderma (1/25), vasculitis (1/25), and dapsone syndrome (1/25). The mean MDA levels were found to be significantly higher in the LMI positive CADRs (P < 0.001) when compared with LMI-negative ones, while no significant difference was seen for GSH (P = 0.100). Furthermore, there was a significant positive correlation between MDA levels and LMI response (r = 0.831, P < 0.001). On the other hand, a negative but statistically insignificant correlation was found between GSH and LMI response (r = -0.248, P = 0.271). CONCLUSION: CADR patients were found to be under oxidative stress based on MDA and GSH levels in the peripheral blood. There is a significant positive correlation of LMI response (against the causative drug) with MDA levels, which strongly associates oxidative stress with the immunopathogenesis in CADRs.

Vitamin A and lipid peroxidation in patients with different forms of leprosy.

Leprosy, a chronic infectious disease, is caused by a Mycobacterium leprae infection. After India, Brazil has the second greatest number of cases in the world. Increase of oxidative stress and antioxidant deficiency are present in infected subjects and can be related to infection progression. We studied alterations in serum levels of lipid peroxidation (LPO) and vitamin A in patients with different forms of leprosy. Four groups of leprosy patients and a control group (healthy subjects) were selected, and their vitamin A serum levels and LPO profile, measured as malonaldehyde (MDA) were measured by spectrophotometric assays. The mean MDA serum levels (micromol/L) were 3.80 +/- 0.5 for control group and 10.54 +/- 1.1 in the leprosy patients and this increase was gradual, being more accentuated in severe forms of the disease. Also, the vitamin A serum levels (microg/dL) were diminished in the infected subjects (38.51 +/- 4.2), mainly in lepromatous form, when compared with the control group (53.8 +/- 5.6). These results indicate that LPO can be an important factor in Mycobacterium leprae infection, which can be related to increases in phagocytic activity and the general breakdown of antioxidants, contributing to an increase of LPO during infection progression. The evaluation of oxidant/antioxidant status in these patients can be an important factor in the treatment, control, and/or prognosis of this disease.

Vitamin A and lipid peroxidation in patients with different forms of leprosy

Leprosy, a chronic infectious disease, is caused by a Mycobacterium leprae infection. After India, Brazil has the second greatest number of cases in the world. Increase of oxidative stress and antioxidant deficiency are present in infected subjects and can be related to infection progression. We studied alterations in serum levels of lipid peroxidation (LPO) and vitamin A in patients with different forms of leprosy. Four groups of leprosy patients and a control group (healthy subjects) were selected, and their vitamin A serum levels and LPO profile, measured as malonaldehyde (MDA) were measured by spectrophotometric assays. The mean MDA serum levels (μmol/L) were 3.80 ± 0.5 for control group and 10.54 ± 1.1 in the leprosy patients and this increase was gradual, being more accentuated in severe forms of the disease. Also, the vitamin A serum levels (μg/dL) were diminished in the infected subjects (38.51 ± 4.2), mainly in lepromatous form, when compared with the control group (53.8 ± 5.6). These results indicate that LPO can be an important factor in Mycobacterium leprae infection, which can be related to increases in phagocytic activity and the general breakdown of antioxidants, contributing to an increase of LPO during infection progression. The evaluation of oxidant/antioxidant status in these patients can be an important factor in the treatment, control, and/or prognosis of this disease.

A hanseníase, doença infecciosa crônica, é causada pelo Mycobacterium leprae. Depois da índia, o Brasil possui o segundo maior número de casos no mundo. O aumento do estresse oxidativo e da deficiência das defesas antioxidantes estão presentes em indivíduos infectados e podem associar-se à progressão da infecção. Foram estudadas alterações nos níveis séricos da peroxidação lipídica e vitamina A em pacientes com diferentes formas de hanseníase. Foram selecionados para o estudo quatro grupos de pacientes com hanseníase e um grupo controle (indivíduos saudáveis) e os níveis séricos de vitamina A e a peroxidação lipídica, medida através do malondialdeído (MDA), foram determinados por métodos espectrofotométricos. Os níveis séricos médios de MDA (μmol/L) foram 3,80 ± 0,5 no grupo controle e 10,54 ± 1,1 nos pacientes com hanseníase. Sendo este aumento gradual e exacerbado nas formas mais severas da doença. Quanto à vitamina A, os níveis séricos (μg/dL) encontraram-se diminuídos nos indivíduos infectados (38.51 ± 4.2), principalmente na forma lepromatosa, quando comparados com o grupo controle (53.8 ± 5.6). Estes resultados indicam que a peroxidação lipídica pode ser um fator importante na infecção mediada pelo Mycobacterium leprae podendo estar relacionada ao aumento da atividade fagocítica pelos macrófagos contribuindo para um aumento da LPO durante a progressão da infecção. A avaliação do perfil oxidante/antioxidante nestes pacientes pode ser um fator importante no tratamento, controle e/ou prognóstico desta doença.