Superoxide dismutase (SOD), advanced oxidation protein products (AOPP), and disease-modifying treatment are related to better relapse recovery after corticosteroid treatment in multiple sclerosis.

OBJECTIVES: The aim of our study was to analyze oxidative stress (OS) markers in multiple sclerosis (MS) patients during relapse and remission and to evaluate the effects of corticosteroid relapse treatment on oxidative status, and also to determine possible relationship between OS markers and relapse disability recovery after corticosteroid treatment. METHODS: Our study included 118 MS patients, (59 relapse/59 remission) 70 females and 48 males, mean age 40.2 ± 9.4 years, and 88 matched healthy controls. Undergoing disease-modifying therapy (DMT) was present in 30.5% of relapse and 88% of remission MS patients. We analyzed in plasma/serum the following: pro-oxidative-antioxidative balance (PAB), nitrates and nitrites (NO3 + NO2), malondialdehyde (MDA), advanced oxidation protein products (AOPP) superoxide dismutase (SOD), catalase (CAT), uric acid, bilirubin, albumin, and transferrin in all patients and additionally after corticosteroid relapse treatment. Neurological disability was measured using the Extended Disability Status Scale (EDSS). RESULTS: Better clinical recovery after relapse treatment was associated with increased baseline SOD, decreased AOPP, and ongoing DMT (all p < 0.05). There was no difference between OS markers in relapse and remission. MS patients had higher MDA, NO3 + NO2, PAB, SOD, CAT, lower AOPP, uric acid, albumin, bilirubin, and transferrin compared to controls (all p < 0.05). Corticosteroids caused significant decrease of all OS markers (all p < 0.05). CONCLUSION: Increased baseline antioxidative activity of SOD and decreased baseline levels of pro-oxidant AOPP along with ongoing DMT were related to better clinical recovery after corticosteroid relapse treatment. Increase of pro-oxidants and antioxidant enzyme activity in relapse and remission confirms ongoing oxidative injury irrelevant of MS clinical presentation.

Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium.

Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1 mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O2·-) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels. Histopathological examination showed signs of inflammation process as previously demonstrated by exposure to Cd. Overall, we ascertained partial liver redox status improvement, compared with the formerly Cd-induced impact.

Oxidative stress induced by chlorpromazine in patients treated and acutely poisoned with the drug.

Background/Aim: Although chlorpromazine (CPZ) is an antipsychotic drug widely used in clinical practice for a long time, its mechanism of action has not been entirely defined. An extremely difficult managing of patients acutely poisoned with CPZ is additional reason for detailed studying its toxicity mechanisms. In this clinical study, we investigated whether the oxidative stress (OS) mediates CPZ toxic effects in the exposed patients. Methods: The patients were organized into 3 groups: the T-group - hospitalized patients receiving therapeutic doses of 75-150 mg CPZ/day; the overdosed group, divided into two subgroups: the group M and the group S - mildly (CPZ serum concentration: 0.21 ± 0.05 mg/L) and severely (CPZ serum concentration: 2.66 ± 0.25 mg/L) poisoned patients, respectively, and the group C (control group of healthy volunteers). Oxidative stress parameters [total antioxidative status (TAS) and malondialdehyde (MDA) in plasma)] and superoxide dismutase (SOD) activity in erythrocytes were measured spectrophotometrically, and CPZ concentrations in serum were monitored chromatographically. One set of measurements was performed in the group C and T, whereas two sets of measurements (after 24 hours and 48 hours) were done in the poisoned patients, groups M and S. Results: A decrease of TAS and increase of SOD activity were obtained in both subgroups of the poisoned patients, compared to the controls and the group receiving therapeutic doses of CPZ. A significant increase of MDA was achieved in severely poisoned patients, compared to all other groups. Conclusion: Changed oxidative stress parameters in patients poisoned with chlorpromazine indicate involvement of oxidative stress in the toxicity mechanism(s) of chlorpromazine.

Agmatine protection against chlorpromazine-induced forebrain cortex injury in rats.

This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.

Oxidative stress, bioelements and androgen status in testes of rats subacutely exposed to cadmium.

The objective of our study was to examine testicular toxicity of cadmium (Cd), focusing on oxidative stress (OS), essential metals and androgenic status and morphological changes. Male Wistar rats [controls and four Cd-subgroups (n = 6) organized according to the exposure (1, 3, 10 and 21 days)] were intraperitoneally (i.p.) treated with 1 mg CdCl2/kg/day. Testicular Cd deposition was noticed from the 1st day. After 10 and 21 days, copper (Cu) and iron (Fe) increased by 60-109% and 43-67%, respectively, while zinc (Zn) decreased by 24-33%. During 1-21 days of the exposure, decrease in testicular total superoxide dismutase (SOD) and total glutathione-s-transferase (GST) activities occurred gradually by 30-78% and 15-84%, respectively, while superoxide anion radical (O2(-)) increased gradually by 114-271%. After 10-21 days, decrease in testicular catalase (CAT) activity appeared by 13-31%. After 21 days, malondialdehyde (MDA) decreased by 44% and the ratio of oxidized glutathione/reduced glutathione (GSSG/GSH) increased by 130% in testes of the rats exposed to Cd. Additionally, decreased testicular testosterone level and the relative testes mass, along with induced microscopic and macroscopic changes were occured, what can be explained as the consequence of instantly developed OS, impaired essential metals status and Cd testicular deposition.