Antioxidative property of T-0970, a new ureidophenol derivative

Suzumura, Kuniharu; Hashimura, Yoshimasa; Kubota, Hitoshi; Ohmizu, Hiroshi; Suzuki, Toshikazu

doi:10.1080/10715760000300261

Cited by 13 publications

(8 citation statements)

References 23 publications

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“…Oxidative stress was successfully assayed by TAS and SOD (Seymen, Seven, Civelek, Yigit, Hatemi & Burcak 1999;O'Brien, Slaughter, Swain, Birmingham, Greenhill, Elcock & Bugelski 2000). Alanine aminotransferase and AST were often used as markers of hepatocellular injury (Seymen et al 1999;O'Brien et al 2000;Suzumura, Hashimura, Kubota, Ohmiza & Suzuki 2000). Superoxide dismutase and GPx, which are involved in protection against active oxygen species, are considered to be potential tools for identi¢cation of stress caused by environmental factors (Roche & Boge 1996).…”

Section: Introductionmentioning

confidence: 99%

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The antioxidant capacity response to hypoxia stress during transportation of characins (Hyphessobrycon callistusBoulenger) fed diets supplemented with carotenoids

Pan

Chien

Wang

2009

Aquaculture Research

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This study aimed to determine whether dietary carotenoid (CD) supplements could a¡ect the antioxidant capacity of characins Hyphessobrycon callistus upon hypoxia stress at live transportation. Two types of CD [astaxanthin (AX), b-carotene (BC)] and their 1:1 combination (MX) at three concentrations (10, 20 and 40 mg kg À 1 ) were supplemented, resulting in nine CD diets. After 8 weeks' rearing, the resulting ¢sh were divided into two subgroups and exposed to hypoxia or normoxia. Hypoxia involved a gradual decrease in dissolved oxygen (DO) from 6.5 to o1.0 mg L À 1 . Normoxia was DO kept in saturation.Hypoxia led to an increase in the total antioxidant status (TAS), superoxide dismutase (SOD), glutathione peroxidases (GPx) and aspartate aminotransferase (AST) activity of blood serum in ¢sh, but had no e¡ect on alanine aminotransferase (ALT). Under hypoxia, ¢sh fed CD diets had lower SOD, GPx and ALT activity than control ¢sh, showing that dietary CD could increase the antioxidant capacity and protection of the liver. Dietary AX was more e¡ective for antioxidant capacity than BC and MX when under hypoxia stress, because GPx, ALT and AST were lower in AX-fed ¢sh. Except TAS, the other four enzyme activities showed decreasing trends with increasing dietary CD concentrations.

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Section: Introductionmentioning

confidence: 99%

“…High AST and ALT generally, but not de¢nitively, indicate the weakening or damage of normal liver function. Alanine aminotransferase and AST were often used as markers of hepatocellular injury (Seymen et al 1999;O'Brien et al 2000;Suzumura, Hashimura, Kubota, Ohmiza & Suzuki 2000).…”

Section: Introductionmentioning

confidence: 99%

The antioxidant capacity response to hypoxia stress during transportation of characins (Hyphessobrycon callistusBoulenger) fed diets supplemented with carotenoids

Pan

Chien

Wang

2009

Aquaculture Research

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“…It has been demonstrated that the iron chelate, ferric nitrilotriacetate (Fe-NTA), is a potent inducer of lipid peroxidation in cells and in animal models (17). It has also been reported that rats intraperitoneally (ip) injected with Fe-NTA show an increase in the level of thiobarbituric acid-reactive substances in liver and an elevation of the plasma levels of aspartate aminotransferase and alanine aminotransferase indicative of hepatic injury (18). Fe-NTA causes renal carcinomas in rats (19) and induces the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in DNA from isolated rat kidney cells (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

<a name="home"></a>Lycopene and ß-carotene protect in vivo iron-induced oxidative stress damage in rat prostate

Matos

Marques

Gomes

et al. 2006

Braz J Med Biol Res

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It has been suggested that iron overload may be carcinogenic. In the present study, we evaluated the effect of plasma and prostate carotenoid concentration on oxidative DNA damage in 12-week-old Wistar rats treated with intraperitoneal (ip) ferric nitrilotriacetate (Fe-NTA) (10 mg Fe/kg). Plasma ß-carotene and lycopene concentrations were measured as a function of time after ip injection of carotenoids (10 mg kg -1 day -1 ß-carotene or lycopene) in rats. The highest total plasma concentration was reached 3 and 6 h after ip injection of lycopene or ß-carotene, respectively. After 5 days of carotenoid treatment, lycopene and ß-carotene were present in the 0.10-0.51 nmol/g wet tissue range in the prostate. Using a sensitive method to detected 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) by HPLC/EC, the level of 8-oxodGuo in rat prostate DNA was significantly higher (6.3 ± 0.6 residues/10 6 dGuo) 3 h after Fe-NTA injection compared with control rats (1.7 ± 0.3 residues/10 6 dGuo). Rats supplemented with lycopene or ß-carotene for 5 days prior to Fe-NTA treatment showed a reduction of about 70% in 8-oxodGuo levels to almost control levels. Compared with control rats, the prostate of Fe-NTA-treated animals showed a 78% increase in malondialdehyde accumulation. Lycopene or ß-carotene pre-treatment almost completely prevented lipid damage. Epidemiological studies have suggested a lower risk of prostate cancer in men reporting a higher consumption of tomato products. However, before associating this effect with tomato sauce constituents, more information is required. The results described here may contribute to the understanding of the protective effects of carotenoids against iron-induced oxidative stress.

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“…Second, we used T‐0970, a water‐ soluble free radical scavenger with a low molecular weight. This compound is considered to enter myocytes more easily than other free radical scavengers, such as SOD, and to scavenge more free radicals than MPG and, therefore, a much greater effect can be expected 8 . The results of the present study demonstrated that a bolus injection of 2.5 mg/kg of T‐0970 and continuous infusion of T‐0970 at a rate of 100 μg/kg per min for 180 min starting at 10 min before reperfusion and continuing until 180 min after reperfusion significantly reduced infarct size.…”

Section: Discussionmentioning

confidence: 99%

“…The water‐soluble low‐molecular weight free radical scavenger 1‐(3‐tret‐butyl‐2‐hydroxy‐5‐methoxyphenyl)‐3‐(3‐pyridylmethyl) urea hydrocloride (T‐0970; synthesized by Tanabe Seiyaku Co. Ltd; Fig. 1) has been reported to scavenge both superoxide anions and hydroxyl radicals in vitro and is considered to be able to enter myocardial cells better than superoxide dismutase (SOD) 8 . Therefore, T‐0970 may have a greater potency to scavenge free radicals during reperfusion and to prevent myocardial reperfusion injury.…”

Section: Introductionmentioning

confidence: 99%

Role Of Protein Kinase C, K_ATP Channels And Dna Fragmentation In The Infarct Size‐Reducing Effects Of The Free Radical Scavenger T‐0970

Hashimoto¹,

Minatoguchi²,

Hashimoto³

et al. 2001

Clin Exp Pharma Physio

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1. In the present study, we investigated the effect of 1-(3-tert-butyl-2-hydroxy-5-methoxyphenyl)-3-(3-pyridylmethyl) urea hydrocloride (T-0970), a novel water-soluble low-molecular weight free radical scavenger, on the generation of hydroxyl radicals in vivo and on myocardial infarct size in an in vivo model of myocardial infarction in rabbits. 2. T-0970 scavenged hydroxyl radicals generated in the myocardium during reperfusion, as assessed by using a microdialysis technique and HPLC in an in vivo model with 30 min coronary occlusion and 30 min reperfusion in rabbits. 3. Another group of rabbits was subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with saline for 190 min from 10 min before occlusion to 180 min after reperfusion. The treatment group (T-0970 group; n = 10) was injected with a bolus 2.5 mg/kg T-0970 and then infused with T-0970 for 190 min from 10 min before reperfusion to 180 min after reperfusion at a rate of 100 microg/kg per min. The T-0970 + CHE group (n = 5) was given chelerythrine (CHE; a selective inhibitor of protein kinase C (PKC); 5 mg/kg, i.v.) 10 min before the administration of T-0970. The T-0970 + 5-HD group (n = 5) was given 5-hydroxydecanoate (5-HD; an inhibitor of mitochondrial K(ATP) channels; 5 mg/kg, i.v.) 10 min before the administration of T-0970. The CHE and 5-HD groups were given CHE (5 mg/kg, i.v.) and 5-HD (5 mg/kg, i.v.) 20 min before reperfusion, respectively. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of the area at risk (AAR). In another series of experiments, the control (n = 5) and T-0970 (n = 5) groups were killed 4 h after reperfusion following 30 min coronary occlusion and DNA fragmentation in myocytes was assessed using in situ dUTP nick end-labelling (TUNEL) at the light microscopic level. 4. Infarct size, as a percentage of AAR, in the T-0970 group was significantly reduced compared with the control group (21+/-4 vs 41+/-4%, respectively; P<0.05). This reduction of infarct size by T-0970 was abolished by pretreatment with CHE and 5-HD. Neither CHE nor 5-HD alone had any effect on infarct size. The percentage of infarcted myocytes with DNA fragmentation by TUNEL in the T-0970 group was significantly reduced compared with the number in the control group (4.0+/-1.5 vs 10.7+/-1.9%, respectively; P<0.05). 5. T-0970, a free radical scavenger, improved reperfusion injury. This effect seemed to be mediated by activation of PKC, the opening of mitochondrial K(ATP) channels and inhibition of DNA fragmentation.

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Antioxidative property of T-0970, a new ureidophenol derivative

Cited by 13 publications

References 23 publications

The antioxidant capacity response to hypoxia stress during transportation of characins (Hyphessobrycon callistusBoulenger) fed diets supplemented with carotenoids

The antioxidant capacity response to hypoxia stress during transportation of characins (Hyphessobrycon callistusBoulenger) fed diets supplemented with carotenoids

<a name="home"></a>Lycopene and ß-carotene protect in vivo iron-induced oxidative stress damage in rat prostate

Role Of Protein Kinase C, K_ATP Channels And Dna Fragmentation In The Infarct Size‐Reducing Effects Of The Free Radical Scavenger T‐0970

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Antioxidative property of T-0970, a new ureidophenol derivative

Cited by 13 publications

References 23 publications

The antioxidant capacity response to hypoxia stress during transportation of characins (Hyphessobrycon callistusBoulenger) fed diets supplemented with carotenoids

The antioxidant capacity response to hypoxia stress during transportation of characins (Hyphessobrycon callistusBoulenger) fed diets supplemented with carotenoids

<a name="home"></a>Lycopene and ß-carotene protect in vivo iron-induced oxidative stress damage in rat prostate

Role Of Protein Kinase C, KATP Channels And Dna Fragmentation In The Infarct Size‐Reducing Effects Of The Free Radical Scavenger T‐0970

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Role Of Protein Kinase C, K_ATP Channels And Dna Fragmentation In The Infarct Size‐Reducing Effects Of The Free Radical Scavenger T‐0970