Protection by pentoxifylline of malathion-induced toxic stress and mitochondrial damage in rat brain

2010 ◽  
Vol 29 (10) ◽  
pp. 851-864 ◽  
Author(s):  
Akram Ranjbar ◽  
Mohammad Hossein Ghahremani ◽  
Mohammad Sharifzadeh ◽  
Abolfazl Golestani ◽  
Mahmood Ghazi-Khansari ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Oxidative Damage ◽  
Rat Brain ◽  
Manganese Superoxide Dismutase ◽  
Brain Homogenate ◽  
Brain Mitochondria ◽  
Alpha Tocopherol ◽  
Protective Effects ◽  
Whole Brain ◽  
Induced Changes

Objective: The objective of this study was to investigate the possible protective effects of pentoxifylline as a phosphodiesterase-5 inhibitor on malathion-induced oxidative damage to rat brain mitochondria. Methods: Rats received malathion (200 mg/kg/day) and pentoxifylline (PTX, 50 mg/kg/day) in combination or alone. Alpha-tocopherol (AT, 15 mg/kg/day) was used as a positive standard. After 1 week of treatment, blood, whole brain tissue, and brain mitochondria were isolated. The activity of enzymatic scavengers such as glutathione peroxidase (GPx), catalase (CAT), copper-zinc superoxide dismutase (Cu/ZnSOD), and manganese superoxide dismutase (MnSOD) were measured. The extents of cellular lipid peroxidation (LPO), nitrotyrosine (NOx), and the ratio of reduced versus oxidized glutathione (GSH/GSSG) were determined. The protein expression of MnSOD was determined in brain mitochondria. Results: Malathion stimulated activities of CAT, Cu/ZnSOD, GPx, and increased LPO and NOx, and decreased GSH/GSSG in whole brain homogenate. The changes in CAT, LPO, GPx, and GSH/GSSG were restored by PTX and AT. In plasma samples, malathion increased CAT, Cu/ZnSOD, and GPx activities, increased LPO, and decreased GSH/GSSG, while PTX and AT attenuated malathion-induced changes in GPx, Cu/ZnSOD, LPO, and GSH/GSSG. In brain mitochondria, malathion enhanced LPO, NOx, CAT, GPx, and MnSOD and decreased GSH/GSSG as compared to controls, whereas PTX and AT restored malathion-induced changes in GSH/GSSG, NOx, GPx, and CAT. Malathion noticeably enhanced expression of MnSOD protein as compared to controls. Malathion decreased viability of mitochondria that was recovered by AT. It is concluded that oxidative damage is at least in part the mechanism of toxicity of malathion in the mitochondria that can be recovered by PTX comparable to AT.

scholarly journals Neutral Sphingomyelinase Modulation in the Protective/Preventive Role of rMnSOD from Radiation-Induced Damage in the Brain

2019 ◽  
Vol 20 (21) ◽  
pp. 5431 ◽  
Author(s):  
Samuela Cataldi ◽  
Antonella Borrelli ◽  
Maria Rachele Ceccarini ◽  
Irina Nakashidze ◽  
Michela Codini ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Nuclear Research ◽  
Protective Effects ◽  
Manganese Superoxide ◽  
Additional Group ◽  
Gene And Protein Expression ◽  
Radiation Induced ◽  
The Brain ◽  
Preventive Role

Studies on the relationship between reactive oxygen species (ROS)/manganese superoxide dismutase (MnSOD) and sphingomyelinase (SMase) are controversial. It has been demonstrated that SMase increases the intracellular ROS level and induces gene expression for MnSOD protein. On the other hand, some authors showed that ROS modulate the activation of SMase. The human recombinant manganese superoxide dismutase (rMnSOD) exerting a radioprotective effect on normal cells, qualifies as a possible pharmaceutical tool to prevent and/or cure damages derived from accidental exposure to ionizing radiation. This study aimed to identify neutral SMase (nSMase) as novel molecule connecting rMnSOD to its radiation protective effects. We used a new, and to this date, unique, experimental model to assess the effect of both radiation and rMnSOD in the brain of mice, within a collaborative project among Italian research groups and the Joint Institute for Nuclear Research, Dubna (Russia). Mice were exposed to a set of minor γ radiation and neutrons and a spectrum of neutrons, simulating the radiation levels to which cosmonauts will be exposed during deep-space, long-term missions. Groups of mice were treated or not-treated (controls) with daily subcutaneous injections of rMnSOD during a period of 10 days. An additional group of mice was also pretreated with rMnSOD for three days before irradiation, as a model for preventive measures. We demonstrate that rMnSOD significantly protects the midbrain cells from radiation-induced damage, inducing a strong upregulation of nSMase gene and protein expression. Pretreatment with rMnSOD before irradiation protects the brain with a value of very high nSMase activity, indicating that high levels of activity might be sufficient to exert the rMnSOD preventive role. In conclusion, the protective effect of rMnSOD from radiation-induced brain damage may require nSMase enzyme.

Protective Effects of the Synthetic Cannabinoids CP55,940 and JWH-015 on Rat Brain Mitochondria upon Paraquat Exposure

2010 ◽  
Vol 35 (9) ◽  
pp. 1323-1332 ◽  
Author(s):  
Carlos Velez-Pardo ◽  
Marlene Jimenez-Del-Rio ◽  
Silvia Lores-Arnaiz ◽  
Juanita Bustamante
Keyword(s):  
Rat Brain ◽  
Synthetic Cannabinoids ◽  
Brain Mitochondria ◽  
Protective Effects ◽  
Rat Brain Mitochondria

Baicalein protects rat brain mitochondria against chronic cerebral hypoperfusion-induced oxidative damage

2009 ◽  
Vol 1249 ◽  
pp. 212-221 ◽  
Author(s):  
Xiao-Li He ◽  
Yue-Hua Wang ◽  
Mei Gao ◽  
Xiao-Xiu Li ◽  
Tian-Tai Zhang ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Rat Brain ◽  
Brain Mitochondria ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Rat Brain Mitochondria

scholarly journals Cardiac Electrophysiological Alterations in Heart/Muscle-Specific Manganese-Superoxide Dismutase-Deficient Mice: Prevention by a Dietary Antioxidant Polyphenol

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Tadahiro Sunagawa ◽  
Takahiko Shimizu ◽  
Akio Matsumoto ◽  
Motoyuki Tagashira ◽  
Tomomasa Kanda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Action Potential ◽  
Heart Muscle ◽  
Chronic Exposure ◽  
Manganese Superoxide Dismutase ◽  
Left Ventricular ◽  
Protective Effects ◽  
Manganese Superoxide ◽  
Dietary Antioxidant

Cardiac electrophysiological alterations induced by chronic exposure to reactive oxygen species and protective effects of dietary antioxidant have not been thoroughly examined. We recorded surface electrocardiograms (ECG) and evaluated cellular electrophysiological abnormalities in enzymatically-dissociated left ventricular (LV) myocytes in heart/muscle-specific manganese-superoxide dismutase-deficient (H/M-Sod2−/−) mice, which exhibit dilated cardiomyopathy due to increased oxidative stress. We also investigated the influences of intake of apple polyphenols (AP) containing mainly procyanidins with potent antioxidant activity. The QRS and QT intervals of ECG recorded in H/M-Sod2−/−mice were prolonged. The effective refractory period in the LV myocardium of H/M-Sod2−/−mice was prolonged, and susceptibility to ventricular tachycardia or fibrillation induced by rapid ventricular pacing was increased. Action potential duration in H/M-Sod2−/−LV myocytes was prolonged, and automaticity was enhanced. The density of the inwardly rectifier K+current (IK1) was decreased in the LV cells of H/M-Sod2−/−mice. The AP intake partially improved these electrophysiological alterations and extended the lifespan in H/M-Sod2−/−mice. Thus, chronic exposure of the heart to oxidative stress produces a variety of electrophysiological abnormalities, increased susceptibility to ventricular arrhythmias, and action potential changes associated with the reduced density ofIK1. Dietary intake of antioxidant nutrients may prevent oxidative stress-induced electrophysiological disturbances.

Oxidative damage induced by a novel porphyrin on rat brain mitochondria and its possible implications in therapy

Redox Report ◽  
1997 ◽  
Vol 3 (3) ◽  
pp. 183-188 ◽  
Author(s):  
S. R. Chatterjee ◽  
J. P. Kamat ◽  
S. J. Shetty ◽  
T. S. Srivastava ◽  
T. P. A. Devasagayam
Keyword(s):  
Oxidative Damage ◽  
Rat Brain ◽  
Brain Mitochondria ◽  
Rat Brain Mitochondria

scholarly journals Protective Effect of PPARγAgonists on Cerebellar Tissues Oxidative Damage in Hypothyroid Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yousef Baghcheghi ◽  
Farimah Beheshti ◽  
Hossein Salmani ◽  
Mohammad Soukhtanloo ◽  
Mahmoud Hosseini
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Drinking Water ◽  
Oxidative Damage ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Group I ◽  
Biochemical Measurements ◽  
Thiol Content

The aim of the current study was to investigate the effects of peroxisome proliferator-activated receptor gamma (PPARγ) agonists on cerebellar tissues oxidative damage in hypothyroid rats. The animals included seven groups: group I (control), the animals received drinking water; group II, the animals received 0.05% propylthiouracil (PTU) in drinking water; besides PTU, the animals in groups III, IV, V, VI, and VII, were injected with 20 mg/kg vitamin E (Vit E), 10 or 20 mg/kg pioglitazone, and 2 or 4 mg/kg rosiglitazone, respectively. The animals were deeply anesthetized and the cerebellar tissues were removed for biochemical measurements. PTU administration reduced thiol content, superoxide dismutase (SOD), and catalase (CAT) activities in the cerebellar tissues while increasing malondialdehyde (MDA) and nitric oxide (NO) metabolites. Vit E, pioglitazone, and rosiglitazone increased thiol, SOD, and CAT in the cerebellar tissues while reducing MDA and NO metabolites. The results of present study showed that, similar to Vit E, both rosiglitazone and pioglitazone as PPARγagonists exerted protective effects against cerebellar tissues oxidative damage in hypothyroid rats.

scholarly journals A Gel Formulation Containing a New Recombinant Form of Manganese Superoxide Dismutase: A Clinical Experience Based on Compassionate Use-Safety of a Case Report

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Lucia Grumetto ◽  
Antonio Del Prete ◽  
Giovanni Ortosecco ◽  
Antonella Borrelli ◽  
Salvatore Del Prete ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Case Report ◽  
Manganese Superoxide Dismutase ◽  
Recombinant Form ◽  
Term Therapy ◽  
Protective Effects ◽  
Manganese Superoxide ◽  
Gel Preparation ◽  
The Right ◽  
Long Term Therapy

Background. We report a case of bilateral posterior subcapsular cataracts (PSCs) in a 24-year-old man with an allergic conjunctivitis history caused by a long-term therapy with glucocorticoids.Case Presentation. The patient showed a visual acuity of 9/10 for both eyes. He followed a therapy with ketotifen and bilastine for four years. During the last six months before our evaluation, he was treated with chloramphenicol and betamethasone, interrupted for onset of cataracts and increased intraocular pressure. We treated him with ophthalmic gel preparation containing a new recombinant form of manganese superoxide dismutase (rMnSOD) at a concentration of 12.5 μg/mL, only for the right eye, while left eye was treated with standard protocol of Bendazac-lysine g 0.5.Conclusion. This case report shows the protective effects of rMnSOD versus PSC disease, probably due to the capacity of rMnSOD of countering free radical species.

scholarly journals Activity of manganese superoxide dismutase in rat brain exposed to acute, chronic, or combined stress

2007 ◽  
Vol 59 (3) ◽  
pp. 39P-40P
Author(s):  
Snezana Pejic ◽  
Vesna Stojiljkovic ◽  
Ana Todorovic ◽  
Jelena Kasapovic ◽  
Snezana Pajovic
Keyword(s):  
Superoxide Dismutase ◽  
Rat Brain ◽  
Manganese Superoxide Dismutase ◽  
Combined Stress ◽  
Manganese Superoxide

scholarly journals Protective effects of oestradiol against cadmium-induced changes in blood parameters and oxidative damage in rats

2014 ◽  
Vol 65 (1) ◽  
pp. 37-46 ◽  
Author(s):  
Jelena Mladenović ◽  
Branka Ognjanović ◽  
Nataša Đorđević ◽  
Miloš Matić ◽  
Veroljub Knežević ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Oxygen Free Radicals ◽  
Redox Balance ◽  
Blood Parameters ◽  
Enzymatic Antioxidants ◽  
Protective Effects ◽  
Antioxidant Defences ◽  
Biochemical Effects ◽  
Endogenous Antioxidants ◽  
Induced Changes

Summary The aim of this study was to investigate the protective effects of oestradiol (E2, 4 mg kg-1 b.w. i.p.) against cadmium-induced (Cd, 2 mg kg-1 b.w. i.p.) blood changes in rats. Cadmium induced a significant decline in haemoglobin, haematocrit, and total erythrocyte, lymphocyte, and thrombocyte count, whereas total leukocytes and granulocytes increased. A significant increase was also observed in serum cholesterol, triglycerides, glucose, AST, and ALT activities, whereas total protein and albumin levels dropped significantly. Administration of E2 in combination with Cd alleviated most of these adverse effects. In terms of oxidative stress, Cd significantly increased oxygen-free radicals (O2 •- and H2O2) in neutrophils and lipid peroxidation in erythrocytes, whereas E2 treatment reversed these changes to control values. Acute Cd poisoning significantly lowered antioxidant enzyme (SOD and CAT) activity and the level of non-enzymatic antioxidants (GSH and vitamin E), while increasing in GSSG. Treatments with E2 reversed Cd-induced effects on the antioxidant defences and significantly lowered Cd-induced oxidative damage in erythrocytes. This study suggests that exogenous E2 effectively restores redox balance in rat erythrocytes and counters adverse haematological and biochemical effects of Cd poisoning. It also improves the antioxidant capacity of erythrocytes, acting in synergy with endogenous antioxidants.

Actions of Atropine, Hemicholinium-3, and Physostigmine on Chlorpromazine-Induced Changes in Rat Brain Monoamines

1974 ◽  
Vol 52 (3) ◽  
pp. 500-507
Author(s):  
Satya P. Bhatnagar
Keyword(s):  
Monoamine Oxidase ◽  
Rat Brain ◽  
Monoamine Oxidase Inhibition ◽  
Brain Monoamines ◽  
Whole Brain ◽  
Synthesis Inhibition ◽  
Oxidase Inhibition ◽  
Induced Changes

The influence of atropine, hemicholinium-3 (HC-3), and physostigmine on the accumulation of monoamines after monoamine oxidase inhibition with pargyline, and on their disappearance after synthesis inhibition with α-methyl-p-tyrosine (α-MT), was investigated in whole brain of normal and chlorpromazine (CPZ)-treated rats. The results disclosed that the accumulation of dopamine (DA) and serotonin (5-HT) is significantly inhibited by atropine and HC-3, as is the loss of DA. None of these drugs affected the noradrenaline (NA) accumulation except for HC-3, which produced a small but statistically significant potentiation. Both atropine and HC-3 increased while physostigmine inhibited the disappearance of NA. These drugs, however, had no effect on the normal cerebral concentrations of monoamines. CPZ substantially increased the accumulation of DA and 5-HT and the loss of DA and NA without affecting their normal concentrations. HC-3, and to some extent atropine, inhibited the action of CPZ on the accumulation of DA and 5-HT. These drugs also inhibited the CPZ-induced accentuation of DA loss but enhanced that of NA. Physostigmine produced the opposite effects. In both normal and CPZ-treated animals, choline, which by itself was ineffective, partly reversed the actions of HC-3 but not that of atropine. These results support the hypothesis of cholinergic–aminergic interaction at the cerebral level and demonstrate the usefulness of HC-3 as a tool in such investigations.

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