Reduction of carbon tetrachloride-induced rat liver injury by IRFI 042, a novel dual vitamin E-like antioxidant

Campo, Giuseppe M.; Squadrito, Francesco; Ceccarelli, S.; Calò, Margherita; Avenoso, Angela; Campo, Salvatore; Squadrito, Giovanni; Altavilla, Domenica

doi:10.1080/10715760100300321

Cited by 66 publications

(37 citation statements)

References 55 publications

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“…In studies performed with rats, Trolox and other vitamin E analogs (a-and g-tocopherol) partially or did not protect against CCl 4 -induced elevation of ALT 6 h after its administration. 49,50 In another work where the effect of vitamin E and IRFI 042, an analogous compound, were evaluated 48 h after CCl 4 administration to rats, a partial reduction of ALT was observed with IRFI 042, but none with vitamin E. 51 Thus, the present study and previous data 52 clearly indicate that reducing CYP2E1 activity could be a better strategy than antioxidants to prevent CCl 4 -induced early hepatotoxicity. Figure 9 Scheme showing lipid peroxidation-dependent and -independent early toxicity induced by CCl 4 .…”

Section: Discussionsupporting

confidence: 49%

Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver

Knockaert

Berson

Ribault

et al. 2012

Laboratory Investigation

113

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Although carbon tetrachloride (CCl 4 )-induced acute and chronic hepatotoxicity have been extensively studied, little is known about the very early in vivo effects of this organic solvent on oxidative stress and mitochondrial function. In this study, mice were treated with CCl 4 (1.5 ml/kg ie 2.38 g/kg) and parameters related to liver damage, lipid peroxidation, stress/defense and mitochondria were studied 3 h later. Some CCl 4 -intoxicated mice were also pretreated with the cytochrome P450 2E1 inhibitor diethyldithiocarbamate or the antioxidants Trolox C and dehydroepiandrosterone. CCl 4 induced a moderate elevation of aminotransferases, swelling of centrilobular hepatocytes, lipid peroxidation, reduction of cytochrome P4502E1 mRNA levels and a massive increase in mRNA expression of heme oxygenase-1 and heat shock protein 70. Moreover, CCl 4 intoxication induced a severe decrease of mitochondrial respiratory chain complex IV activity, mitochondrial DNA depletion and damage as well as ultrastructural alterations. Whereas DDTC totally or partially prevented all these hepatic toxic events, both antioxidants protected only against liver lipid peroxidation and mitochondrial damage. Taken together, our results suggest that lipid peroxidation is primarily implicated in CCl 4 -induced early mitochondrial injury. However, lipid peroxidation-independent mechanisms seem to be involved in CCl 4 -induced early hepatocyte swelling and changes in expression of stress/defense-related genes. Antioxidant therapy may not be an efficient strategy to block early liver damage after CCl 4 intoxication.

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Section: Discussionsupporting

confidence: 49%

Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver

Knockaert

Berson

Ribault

et al. 2012

Laboratory Investigation

113

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“…As some antioxidants may scavenge free radicals and inhibit lipid peroxidation, treatment with several antioxidants such as vitamin E and thiopalmitic acid has been shown to protect against CCl 4 -induced hepatic damage [2][3][4]13]. In addition to chemically synthesized antioxidants, dietary antioxidants also protect against CCl 4 -induced lipid peroxidation [28].…”

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confidence: 99%

Protective Effect of a Lignan-Containing Flaxseed Extract against CCl4-Induced Hepatic Injury.

et al. 2002

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ABSTRACT. Carbon tetrachloride (CCl 4 ) -induced hepatotoxicity is a commonly used model for investigating lipid peroxidation-related tissue injury. In the present study, the effect of flaxseed extract was observed on histological sections, glutathione-content and DNA strand breaks. Lignan-containing flaxseed extract (1.6 g/kg body weight/day) was daily administered with intragastric injection to rat s for three days, on the fourth day, CCl 4 (2 g/kg) was intraperitoneally injected. Liver tissue was sampled at 24 hr after administering CCl 4 . Livernecrosis was observed in CCl 4 -injected rats without pretreatment of flaxseed extract. Pretreatment of flaxseed extract reduced extent of the necrosis found 24 hr after the intraperitoneal administration of CCl 4 . Pretreatment of flaxseed extract protect against CCl 4 -induced decrease of reduced glutathione-content measured from reactions with 5,5'-dithiobis-(2-nitrobenzoic acid) and also protect against the elevation of DNA strand breaks in the liver cells measured by comet assay. Flaxseed-extract appears to protect liver cells agai nst CCl 4 -induced necrosis. KEY WORDS: carbon tetrachloride-induced liver injury, comet assay, flaxseed extract, glutathione, lignan.

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“…The oxidation of unsaturated fatty acids in biological membrane leads to a reduction in membrane fluidity and disruption of membrane structure and function 19 . MDA the end point of lipid per oxidation was also reported to be higher in carcinomatous tissue than in non diseased organs 20 .…”

Section: Figure 1: (A) Histology Of Control Mice Shows the Normal LIVmentioning

confidence: 99%

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2012

IJPSR

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The purpose of this study was to investigate the experimentally possible antitumor effect and antioxidant role of methanolic extract of Tabebuia rosea leaves against Dalton's ascetic lymphoma (DAL) induced Swiss albino mice. The methanolic extract of Tabebuia rosea (METR) was administered at the doses of 100mg/kg, 200mg/kg in mice for 14 days after 24hours of DAL inoculation. The effects of METR on the growth of bodyweight, MST, viable and nonviable cell count, Tumor volume, Packed Cell Volume (PCV), life span of DAL bearing mice were studied. Hematological profile and liver biochemical parameters (lipid per oxidation, antioxidant enzymes) were also estimated. Treatment with METR decreased the tumor volume and viable cell count thereby increasing the lifespan of DAL bearing mice. Alteration in the Hematological parameters, protein, PCV occurred because of DLA inoculation, were almost restored in METR treated groups. The effect of METR also decreases the levels of lipid peroxidation and increases the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). The histopathological results showed the loss of liver hepatocytes in DLA bearing mice. However, a mouse treated with METR extract improved the liver and rearranged more or less normal architecture. The present work revealed that the METR exhibits significant antitumor and anti-oxidant activity in vivo. These results support the traditional use of Tabebuia rosea and the alcoholic seed extract is a potent source of anticancer compounds that could be utilized pharmaceutically.

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Reduction of carbon tetrachloride-induced rat liver injury by IRFI 042, a novel dual vitamin E-like antioxidant

Cited by 66 publications

References 55 publications

Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver

Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver

Protective Effect of a Lignan-Containing Flaxseed Extract against CCl4-Induced Hepatic Injury.

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