Mechanisms and biological relevance of lipid peroxidation initiation

Dix, Thomas A.; Aikens, John

doi:10.1021/tx00031a001

Cited by 319 publications

(182 citation statements)

References 217 publications

(363 reference statements)

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“…Hepatic damage has been shown to be associated with lipid peroxidation induced by CsA (Rezzani, 2006;Pari & Sivasankari, 2008). Lipid peroxidation usually leads to changes in the permeability and fluidity of the biological membrane and can dramatically affect cell integrity (Dix & Aikens, 1993). The increased hepatic MDA level (the by-product of lipid peroxidation) in CsA-alone-treated rats may implicate oxidative damage in the liver (Rezzani, 2006;Pari & Sivasankari, 2008).…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats

Akool

2015

Pharmaceutical Biology

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Context: Cyclosporin A (CsA) is one of the most important immunosuppressive agents. However, its clinical use is strongly limited by several side effects including hepatotoxicity which remains a major clinical problem. Involvement of reactive oxygen species (ROS) in CsAinduced hepatotoxicity has been reported. Objective: This study investigates the potential protective role of wheat germ oil (WGO) as an antioxidant against CsA-induced hepatotoxicity. Materials and methods: Twenty-four male Wistar albino rats (six animals in each group) received castor oil, the vehicle of CsA i.p. (control) or either CsA (25 mg/kg/d i.p.), WGO (900 mg/kg/d by oral gavage), or CsA in combination with WGO daily for 21 d. Results: CsA administration significantly increased serum levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, an increase in lipid peroxidation, inducible NO-synthase (iNOS), and NF-kB expression were observed in hepatic tissues of CsA-alone-treated rats. Furthermore, significant reduction in the hepatic content of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) was also observed in CsA-alone-treated animals. Moreover, histopathological changes occurred in CsA-alonetreated rats. Concomitant administration of WGO along with CsA improved all these parameters. Most interestingly, the immunosuppressive effect of CsA was not affected by WGO. Conclusion: The present study suggests that concomitant use of WGO might be useful in reducing liver toxicity induced by CsA via inhibition of ROS, iNOS, and NF-kB expression.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats

Akool

2015

Pharmaceutical Biology

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“…The lipid peroxidation process influences membrane fluidity as well as the integrity of biomolecules associated with the membrane (membrane bound proteins or cholesterol). Since these lipids in fish are in close proximity to electron transport chains and heme iron proteins, which can act as sources of reactive oxygen species under normal conditions, the lipids may sustain high degrees of damage (Dix and Aikens, 1993). These highly oxidizable lipids may then, in turn, attack nearby proteins causing the formation of an excess of protein carbonyls (Almroth et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Induction of hepatic enzymes and oxidative stress in Chinese rare minnow (Gobiocypris rarus) exposed to waterborne hexabromocyclododecane (HBCDD)

Zhang¹,

Yang²,

Xu³

et al. 2008

Aquatic Toxicology

143

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“…The chemical species known to form M 1 dG in vitro, namely MDA and base propenals, arise from different sources. Lipids represent a major target for free radicals (26), and peroxidation of PUFA generates a host of reactive electrophiles, many of which have been implicated in the formation of DNA adducts, such as the etheno adducts of dG, dA, and dC (27). In a similar manner, a Sole fatty acid source in defined culture media (see "Experimental Procedures").…”

Section: Discussionmentioning

confidence: 99%

Chemical and Biological Evidence for Base Propenals as the Major Sourceof the Endogenous M1dG Adduct in CellularDNA

Zhou

Taghizadeh

Dedon

2005

Journal of Biological Chemistry

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The endogenous DNA adduct, M 1 dG, has been shown to arise in vitro in reactions of dG with malondialdehyde (MDA), a product of both lipid peroxidation and 4-oxidation of deoxyribose in DNA, and with base propenals also derived from deoxyribose 4-oxidation. We now report the results of cellular studies consistent with base propenals, and not MDA, as the major source of M 1 dG under biological conditions. As a foundation for cellular studies, M 1 dG, base propenals, and MDA were quantified in purified DNA treated with oxidizing agents known to produce deoxyribose 4-oxidation. The results revealed a consistent pattern; Fe 2؉ -EDTA and ␥-radiation generated MDA but not base propenals or M 1 dG, whereas bleomycin and peroxynitrite (ONOO ؊ ) both produced M 1 dG as well as base propenals with no detectable MDA. These observations were then assessed in Escherichia coli with controlled membrane levels of polyunsaturated fatty acids (PUFA). ONOO ؊ treatment (2 mM) of cells containing no PUFA (defined medium with 18:0/stearic acid) produced 6.5 M 1 dG/10 7 deoxynucleotides and no detectable lipid peroxidation products, including MDA, as compared with 3.8 M 1 dG/ 10 7 deoxynucleotides and 0.07 g/ml lipid peroxidation products with control cells grown in a mixture of fatty acids (0.5% PUFA) mimicking Luria-Bertani medium. In cells grown with linoleic acid (18:2), the level of PUFA rose to 54% and the level of MDA rose to 0.14 g/ml, whereas M 1 dG fell to 1.4/10 7 deoxynucleotides. Parallel studies with ␥-radiation revealed levels of MDA similar to those produced by ONOO ؊ but no detectable M 1 dG. These results are consistent with base propenals as the major source of M 1 dG in this model cell system.

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Mechanisms and biological relevance of lipid peroxidation initiation

Cited by 319 publications

References 217 publications

Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats

Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats

Induction of hepatic enzymes and oxidative stress in Chinese rare minnow (Gobiocypris rarus) exposed to waterborne hexabromocyclododecane (HBCDD)

Chemical and Biological Evidence for Base Propenals as the Major Sourceof the Endogenous M1dG Adduct in CellularDNA

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