Antiradical effects in l-propionyl carnitine protection of the heart against ischemia-reperfusion injury: The possible role of iron chelation

Reznick, Abraham Z.; Kagan, Valerian E.; Ramsey, R.R.; Tsuchiya, Masahiko; Khwaja, Shamsuddin; Serbinova, E. A.; Packer, Lester

doi:10.1016/0003-9861(92)90589-o

Cited by 150 publications

(88 citation statements)

References 30 publications

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“…47,48 It should also be noted that although carnitine lacks activity to scavenge free radicals, this amino acid shows properties similar to that of antioxidants. 26,27 The protective effects of carnitine and its acylesters might reflect their activities to improve energy metabolism and repair oxidized membrane/lipid bilayers, 49,50 thereby suppressing the release of free electrons from mitochondrial electron transport systems, a prerequisite reaction to generate free radicals. The molecular mechanism by which carnitine suppressed hepatic injury and eventual hepatocarcinogenesis should be studied further.…”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24][25] It is thought that carnitine shows its protective effects on mitochondria and on whole cells by inhibiting free fatty acid-induced mitochondrial membrane damage and/or its secondary effects. 22,26,27 Using the hypothesis that oxidative injury induced during the process of hepatocarcinogenesis in LEC rats might be inhibited by carnitine, we investigated whether this agent could prevent inflammatory damage and hepatocarcinogenesis in LEC rats.…”

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confidence: 99%

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L‐carnitine inhibits hepatocarcinogenesis via protection of mitochondria

Chang

Nishikawa

Nishiguchi

et al. 2004

Intl Journal of Cancer

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Hepatocellular carcinoma is usually preceded by chronic inflammation. However, the molecular mechanism in hepatocarcinogenesis is not well known. Recently, we reported that mitochondrial dysfunction plays an important role in hepatocarcinogenesis via the production of free radicals. Furthermore, we proved that L-carnitine effectively protects mitochondrial function in vivo. Therefore, we investigated whether long-term administration of L-carnitine could prevent hepatitis and subsequent hepatocellular carcinoma in Long-Evans Cinnamon rats that are often analyzed as a model of hepatocarcinogenesis. The results indicated that oxidative stress elicited from abnormally accumulated copper increased the amount of free fatty acids, thereby inducing mitochondrial dysfunction, resulting in cell death and enhanced secondary generation of reactive oxygen species, which were significantly inhibited by carnitine treatment. Finally, the occurrence of placental glutathione S-transferase-positive foci as a marker for preneoplastic lesions and hepatocarcinogenesis were significantly inhibited by L-carnitine. These facts suggest that mitochondrial injury plays an essential role in the development of hepatocarcinogenesis and that the clinical use of carnitine has excellent therapeutic potential in individuals with chronic hepatitis.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

L‐carnitine inhibits hepatocarcinogenesis via protection of mitochondria

Chang

Nishikawa

Nishiguchi

et al. 2004

Intl Journal of Cancer

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“…18) Finally, absorbance at 370 nm of guanidine hydrochloride solution was measured and carbonyl concentration was calculated as follows.…”

Section: Measurement Of Protein Carbonyl Groupmentioning

confidence: 99%

Contribution of Nitric Oxide to Potassium Bromate-Induced Elevation of Methaemoglobin Concentration in Mouse Blood.

Watanabe

Togashi

Fukui

2002

Biological & Pharmaceutical Bulletin

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Bromate is frequently detected in tap water and bottled water, since it is an inorganic oxyhalide disinfection by-product, which is formed when drinking water supplies undergo ozonation, an advanced wastewater treatment technique. 1,2) Potassium bromate (KBrO 3 ) is a renal carcinogen and is classified as a group 2B (possibly carcinogenic to humans) by the International Agency for Research on Cancer, 3,4) as are bleomycin and carbon tetrachloride, etc. However, KBrO 3 is generally used as an oxidizing agent for the treatment of wheat flour and as a constituent in cold-wave hair solutions. Acute exposure to KBrO 3 causes not only kidney failure 5,6) but also neuropathological disorder, such as vertigo, tinnitus, and hearing loss. 7,8) Potassium bromate is known to cause oxidative modification of lipid, protein and DNA bases in the kidney, which has usually been thought to contribute to its renal carcinogenic properties.9,10) Methaemoglobinemia and cyanosis in the incipient stage of renal damage are also known to be caused by KBrO 3 .11) Acquired but not heritable methaemoglobinemia is thought to be caused by the oxidative modification of haemoglobin (Hb) by certain chemicals, such as amyl nitrite and acetanilide, since the iron in the haem rings of Hb is in the Fe 2ϩ state and Hb oxidation is speeded up by the presence of nitrite or certain transition metal ions, especially copper.12) So far, KBrO 3 has been regarded as the direct oxidant of Hb as chlorate 13) but no details of KBrO 3 -induced elevation of methaemoglobin (MetHb) concentration in blood have been examined. Previously KBrO 3 -induced renal oxidative stress and kidney damage were reported to be mainly attributable to the reduction of cytoplasmic glutathione peroxidase (GPx) activity, probably caused by the enhanced production of NO and peroxynitrite (ONOO Ϫ ).14) Therefore, it is possible that KBrO 3 -induced methaemoglobinemia is also related to the change in GPx activity resulting from the enhancement of NO production in blood vessels. In this report, the effects of the GPx mimic ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) on the elevation of MetHb concentration, the enhancement of NO production and the attenuation of GPx activity by KBrO 3 are examined to clarify the significant impact of NO on KBrO 3 -induced methaemoglobinemia. In addition, the effect of ebselen on KBrO 3 -induced renal oxidative stress and kidney damage was comparatively investigated. MATERIALS AND METHODS ChemicalsGlutathione reductase from bakers yeast (EC 1.6.4.2), nitrate reductase from aspergillus species (EC 1.6.6.2), Hb, MetHb, reduced glutathione (GSH) and oxidized glutathione were purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.). 2,4-Dinitrophenylhydrazine (DNPH) was obtained from Tokyo Chemical Industry Co. (Tokyo, Japan). KBrO 3 , potassium cyanide, sodium hydrosulfite and ebselen were purchased from Wako Pure Chemical Industries (Osaka, Japan). 1-Hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7), 3-(4-morpholinyl) sydnonimine hydroc...

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“…Measurement of Serum Creatinine Level ---Serum creatinine level was measured with Creatinine Test-Wako (Wako Pure Chemical Industries, Japan). Measurement of Protein Carbonyl Group ---Protein carbonyl group in kidney was assayed by the method of Reznick et al 6) Absorbance at 370 nm of guanidine hydrochloride solution was measured using Hitachi U-2000 Spectrophotometer (Hitachi Co., Tokyo, Japan). Carbonyl concentration was calculated as follows, C (µM) = OD 370 × 45.45.…”

Section: Introductionmentioning

confidence: 99%

Contribution of Glutathione Peroxidase and Nitric Oxide to Potassium Bromate-Induced Oxidative Stress and Kidney Damage in Mice.

Watanabe

Yoshimura

Fukui

2001

JOURNAL OF HEALTH SCIENCE

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In order to confirm the participation of peroxynitrite in potassium bromate (KBrO 3 )-induced oxidative stress and kidney damage in mice, we investigated effects of administration of nitric oxide (NO) synthase inhibitor on them. Cytoplasmic glutathione peroxidase (GPx) activity remarkably decreased within 3 hr after KBrO 3 administration, and then oxidative stress started to occur. However, kidney damage occurred 24 hr after KBrO 3 administration. Pre-administered N G -monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, suppressed KBrO 3 -induced oxidative stress and kidney damage. However, no effect of L-NMMA was observed on the KBrO 3 -induced reduction of cytoplasmic GPx activity. These results suggest that reduction of cytoplasmic GPx activity resulted from the KBrO 3 administration initiates oxidative stress and that NO also participates in the promotion of KBrO 3 -induced oxidative stress and kidney damage.

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Antiradical effects in l-propionyl carnitine protection of the heart against ischemia-reperfusion injury: The possible role of iron chelation

Cited by 150 publications

References 30 publications

L‐carnitine inhibits hepatocarcinogenesis via protection of mitochondria

L‐carnitine inhibits hepatocarcinogenesis via protection of mitochondria

Contribution of Nitric Oxide to Potassium Bromate-Induced Elevation of Methaemoglobin Concentration in Mouse Blood.

Contribution of Glutathione Peroxidase and Nitric Oxide to Potassium Bromate-Induced Oxidative Stress and Kidney Damage in Mice.

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