Oxygen Free Radical Scavenging Enzymes Research Articles

Rapid classification of a novel ALS-causing I149S variant in superoxide dismutase-1

Variants of the oxygen free radical scavenging enzyme superoxide dismutase-1 (SOD1) are associated with the neurodegenerative disease amyotrophic lateral sclerosis (ALS). These variants occur in roughly 20% of familial ALS cases, and 1% of sporadic ALS cases. Here, we identified a novel SOD1 variant in a patient in their 50s who presented with movement deficiencies and neuropsychiatric features. The variant was heterozygous and resulted in the isoleucine at position 149 being substituted with a serine (I149S). In silico analysis predicted the variant to be destabilizing to the SOD1 protein structure. Expression of the SOD1I149S variant with a C-terminal EGFP tag in neuronal-like NSC-34 cells resulted in extensive inclusion formation and reduced cell viability. Immunoblotting revealed that the intramolecular disulphide between Cys57 and Cys146 was fully reduced for SOD1I149S. Furthermore, SOD1I149S was highly susceptible to proteolytic digestion, suggesting a large degree of instability to the protein fold. Finally, fluorescence correlation spectroscopy and native-PAGE of cell lysates showed that SOD1I149S was monomeric in solution in comparison to the dimeric SOD1WT. This experimental data was obtained within 3 months and resulted in the rapid re-classification of the variant from a variant of unknown significance (VUS) to a clinically actionable likely pathogenic variant.

PROTECTIVE EFFECT OF BROCCOLI AND FERULIC ACID ON IMIDACLOPRID-INDUCED HEPATOTOXICITY IN RAT

Imidacloprid may induce oxidative stress leading to generate free radicals and alternate oxygen free radical scavenging enzyme system. This study aims to investigate the hepatoprotective effect of broccoli water extract and ferulic acid on imidacloprid induced oxidative stress and DNA damage in male albino rats. Rats were co-treated with broccoli water extract (200 mg/kg) or ferulic acid (20 mg/kg) with imidacloprid (80 mg/kg) orally for 28 days.The results revealed that imidacloprid induced high serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). However, administration of broccoli and ferulic acid reduced these parameters. Broccoli and ferulic acid significantly (P<0.05) attenuated the imidacloprid-induced increases in lipid peroxidation (LPO), tumor necroses factor α (TNF-α) and nitric oxide (NO) contents and meyloperoxidase (MPO), glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD) activities. Imidacloprid decreased reduced glutathione (GSH) while co-treatment with broccoli and ferulic acid significantly (P<0.05) improved the level of GSH. DNA damage as assessed by comet assay was increased in imidacloprid-treated group. However, DNA damage was decreased in broccoli and ferulic acid treated groups. The possible mechanism of broccoli and ferulic acid extract on imidacloprid might be due to decreasing oxidative stress (LPO, NO and DNA damage) and increasing GSH content. Thus, broccoli and ferulic acid was suggested to protected rat’s liver against imidacloprid-induced oxidative stress and DNA damage in liver. Keywords : broccoli, ferulic acid, imidacloprid, DNA damage, oxidative stress, GSH

Antioxidant role of propolis extract against oxidative damage of testicular tissue induced by insecticide chlorpyrifos in rats

Pesticides induce oxidative stress leading to generate free radicals and alternate the antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the oral toxicity of chlorpyrifos toward male rat and the oxidative stress of the sub-lethal dose (9mg/kg; 1/25 LD50) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities of testicular tissue. Also, the protective effects of propolis extract (50mg/kgb.w.) alone or in combination with chlorpyrifos were investigated. The oral administration of chlorpyrifos significantly caused elevation in LPO level by 1.79-fold as compared to control. The activities of antioxidant enzymes including CAT, SOD, GPx and GST were decreased significantly (23.66%, 27.75%, 29.13% and 11.52%) as well as the level of GSH decreased by 21.97% in testicular tissue as compared to control animals. Co-administration of propolis extract with chlorpyrifos or alone in male rats decreased LPO level, normalized CAT, SOD GPx and GST activities, while GSH content was increased in testicular tissue. We conclude that propolis extract significantly reduces chlorpyrifos-induced oxidative stress in rat testis and the protective effect of the pre-treatment with propolis extract as attenuating agent could be due to its antioxidant properties.

Review Article: Does kombucha tea attenuate the hepato-nepherotoxicity induced by a certain environmental pollutant?

Trichloroethylene (TCE) may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. The aim of this study was to investigate the protective role of oral administration of kombucha tea in rats with TCE as an environmental pollutant. Methods: Twenty male albino rats were divided into four groups: the control group treated with vehicle, Kombucha (KT)-treated group, TCE-treated group and KT/TCE-treated group. Liver and kidney lipid peroxidation, glutathione content, nitric oxide (NO) and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGTP) and lactate dehydrogenase (LDH) activities were also measured. Results: TCE administration increased the malondialhyde (MDA) and NO contents in liver and kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGTP and LDH activities in serum, whereas it decreased the glutathione (GSH) level in liver and kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. Conclusion: The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to people who deal with these chemicals.

Protective effect of vitamin C against chlorpyrifos oxidative stress in male mice

Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of chlorpyrifos toward male mice and the oxidative stress of the sub-lethal dose (1/10 LD 50) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-S-transferase (GST) activities. Also, the protective effects of vitamin C (200 mg/kg body weight, bw) 30 min before or after administration of chlorpyrifos were investigated. The results demonstrated that the LD 50 value of chlorpyrifos was 134.95 mg/kg bw. The oral administration of 13.495 mg/kg chlorpyrifos significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD and GST. However, GPx activity remained unchanged, while the level of GSH and G6PD activity were decreased. Vitamin C treatment to chlorpyrifos intoxicated mice decreased LPO level and GST activity, normalized CAT, SOD and G6PD activities, while GSH content was increased. We conclude that vitamin C significantly reduces chlorpyrifos-induced oxidative stress in mice liver and the protective effect of the pre-treatment with vitamin C is better than the post-treatment.

The role of vitamin C as antioxidant in protection of oxidative stress induced by imidacloprid

Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of imidacloprid toward male mice and the oxidative stress of the sublethal dose (1/10 LD 50) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and activities of the antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione- s-transferase (GST). Also, the protective effect of vitamin C (200 mg/kg bw) 30 min before or after administration of imidacloprid were investigated. The results demonstrated that the median lethal dose (LD 50) of imidacloprid after 24 h was 149.76 mg/kg bw. The oral administration of 14.976 mg/kg imidacloprid significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD, GPx and GST. However, G6PD activity remained unchanged, while the level of GSH content was decreased. In addition, the results showed that vitamin C might ameliorate imidacloprid-induced oxidative damage by decreasing LPO and altering antioxidant defense system in liver. The protective effect of the pre-treatment with vitamin C against imidacloprid-induced oxidative stress in liver mice is better than the post-treatment.

Protective effects of dietary ginger (Zingiber officinales Rosc.) on lindane-induced oxidative stress in rats.

The protective effect of dietary feeding of Zingiber officinales Rosc. (ginger) against lindane-induced oxidative stress was investigated in male albino rats. Oxidative stress was monitored by estimating the extent of lipid peroxidation, activities of the oxygen free radical (OFR) scavenging enzymes superoxide dismutase (SOD) and catalase (CAT) and the status of the glutathione redox cycle antioxidants. Lindane administration (30 mg/kg bw orally for 4 weeks) was associated with enhanced lipid peroxidation and compromised antioxidant defenses in rats fed a normal diet. Concomitant dietary feeding of ginger (1%w/w) significantly attenuated lindane-induced lipid peroxidation, accompanied by modulation of OFR scavenging enzymes as well as reduced glutathione (GSH) and the GSH dependent enzymes glutathione peroxidase (Gpx), glutathione reductase (GR) and glutathione-S-transferase (GST) in these rats. These findings suggest that a diet containing naturally occurring compounds is effective in exerting protective effects by modulating oxidative stress.

Evaluation of oxidative stress in some cases of argimone oil poisoning during a recent outbreak of epidemic dropsy in India

The study was designed to evaluate the oxidative stress and modulation of anti-oxidant enzymes in 10 accidental argimone oil poisoning cases admitted in a hospital in Delhi, India during a recent outbreak of epidemic dropsy in 1998. Serum malondialdehyde (MDA) level, oxygen free-radical scavenging enzymes such as superoxide dismutase (SOD) and catalase (CAT), and glutathione (GSH) and related enzymes, e.g. glutahione reductase (GR), glutathione peroxidase (GPx), gamma glutamyl transpeptidase (GGT) and glutathione-S-transferase (GST) in erythrocytes were assayed. The sanguinarine level in serum was measured by high-performance liquid chromatography. The serum MDA level was higher and the GSH level in erythrocytes was lower in argimone oil poisioning cases than those in controls. There was a significant decrease in SOD and GPx activities in erythrocytes of epidemic dropsy cases but no changes were observed in CAT, GR and GST assay. The depletion of GSH in erythrocytes, serum MDA level and clinical severity were dependent on serum sanguinarine level. The results indicate that sanguinarine (argimone oil) poisoning creates an oxidative stress in humans. The oxidative stress and differential modulation of anti-oxidant enzymes by sanguinarine might play a pathogenic role in epidemic dropsy, which suggests the incorporation of anti-oxidant drugs in the treatment protocol of the disease.

Effects of Combined Superoxide Dismutase and Catalase on Somatosensory Evoked Potentials and Neuropathologic Changes in Asphyxiated Newborn Lambs

The lamb model of neonatal asphyxia has been used to describe changes in cerebral blood flow, oxygen metabolism and mitochondrial function following a standard asphyxial insult. In addition, abnormalities in cerebral hemodynamics and mitochondrial function after asphyxia have been associated with injury mediated by oxygen free radicals. The purpose of this investigation was to describe changes in brainstem auditory and somatosensory evoked potentials and pathologic changes after asphyxia in the newborn lamb. In addition, the hypothesis that treatment with the oxygen free radical scavenging enzymes superoxide dismutase and catalase would enhance postasphyxia recovery of evoked potentials and ameliorate pathologic injury was tested. Electrophysiologic and pathologic abnormalities after asphyxia were demonstrated, but treatment with oxygen radical scavengers had no effect on these abnormalities.

Biochemical effects of some pesticides on lipid peroxidation and free-radical scavengers

Oxidative stress was studied in blood samples obtained from lindane, malathion and propoxur poisoning cases admitted to the Guru Teg Bahadur Hospital, Delhi and evaluated for lipid peroxidation, oxygen free radical (OFR) scavenging enzymes, and glutathione (GSH) and related enzymes. Acetylcholine esterase (AChE), gamma glutamyl transpeptidase (GGT) and GSH level were also assayed in lymphocytes. The level of thiobarbituric acid reacting substances and activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and GGT were increased and GSH level was decreased in pesticide poisoning. Apparently lindane (at the concentration examined) was more potent than malathion and propoxur in producing alteration in lipid peroxidation, GSH related parameters and OFR scavenging enzymes. However, AChE activity and GSH level in lymphocytes of malathion poisoning cases were reduced and GGT activity was enhanced in comparison to control subjects. The present results suggest that OFR scavenging enzymes were induced while combating oxidative stress in a differential manner in organochlorine, organophosphate and carbamate poisoning. Increased lipid peroxidation, coupled with altered levels of GSH and OFR scavenging enzymes in the blood are discussed in the light of oxidative stress.