Intramuscular Administration of Very High Dose of a‐Tocopherol Protects Liver from Severe Ischemia/Reperfusion Injury

Giakoustidis, Dimitrios; Παπαγεωργίου, Γεώργιος; Iliadis, Stavros; Kontos, Nicholas; Kostopoulou, Evanthia; Papachrestou, Aikaterine; Tsantilas, Dimitrios; Spyridis, Charalampos; Takoudas, D; Botsoglou, Nikolaos; Dimitriadou, A.; Giakoustidis, Efthymios

doi:10.1007/s00268-002-6271-2

Cited by 49 publications

(39 citation statements)

References 24 publications

(19 reference statements)

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“…The end production of lipid peroxidation includes aldehydes, hydrocarbon gases, and MDA. MDA is a sensitive index of lipid peroxidation [18,41] . Bertelli et al [33] suggested that MDA formation was reduced in the ischemic-reperfused myocardium of resveratrol-treated rats.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

Gedik¹,

Gırgın²,

Öztürk³

et al. 2008

WJG

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AIM:To investigate the effects of resveratrol on liver ischemia/reperfusion (I/R) injury in rats. METHODS: A total of 40 male Sprague-Dawley rats weighing 240-290 g were randomized into four groups of ten: (1) controls: data from unmanipulated animals; (2) sham group: rats subjected to the surgical procedure, except for liver I/R, and given saline; (3) I/R group: rats underwent liver ischemia for 45 min followed by reperfusion for 45 min; (4) I-R/Resveratrol group: rats pretreated with resveratrol (10 µmol/L, iv). Liver tissues were obtained to determine antioxidant enzyme levels and for biochemical and histological evaluation. RESULTS: Plasma aminotransferase activities were higher in the I/R group than in the I-R/Resveratrol group. Malondialdehyde levels and the hepatic injury score decreased, while superoxide dismutase, catalase, and glutathione peroxidase levels increased in group 4 compared to group 3. In group 4, histopathological changes were significantly attenuated in resveratroltreated livers. CONCLUSION: These results suggest that resveratrol has protective effects against hepatic I/R injury, and is a potential therapeutic drug for ischemia reperfusionrelated liver injury.

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Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

Gedik¹,

Gırgın²,

Öztürk³

et al. 2008

WJG

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“…ble antioxidant in biological systems and has been proven effective in reducing oxidative stress and hepatocellular damage in both clinical and preclinical trials in doses from 10 to 300 mg/kg. 27,31,32 Ascorbic acid is a water-soluble antioxidant known to reduce oxidative stress with maximal hepatoprotective effects at a dose of 100 mg/kg. [28][29][30] Therefore, we examined the effects of ␣-tocopherol (300 mg/kg) and ascorbic acid (100 mg/kg) on GSH levels, early hepatocellular damage, late tissue necrosis, apoptosis, and accelerated tumor growth.…”

Section: I/r Accelerates the Local Outgrowth Of Preestablished Liver mentioning

confidence: 99%

“…[17][18][19] These include alternative clamping techniques such as ischemic preconditioning 8,[20][21][22][23] and intermittent clamping [24][25][26] as well as pharmacological intervention with antioxidants such as ␣-tocopherol and ascorbic acid. [27][28][29][30][31][32] We evaluated whether those strategies cross-protect the liver against (accelerated) outgrowth of micrometastases in this model.…”

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confidence: 99%

Ischemia/reperfusion accelerates the outgrowth of hepatic micrometastases in a highly standardized murine model

Bilt¹,

Kranenburg²,

Nijkamp³

et al. 2005

Hepatology

159

131

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Mortality in colorectal cancer is associated with the development of liver metastases. Surgical removal of these tumors is the only hope for cure, but recurrence is common. During liver surgery, ischemia/reperfusion (I/R) often occurs as a result of hemorrhage or vascular clamping. Although the adverse effects of I/R on postoperative liver function are well documented, the influence of I/R on the outgrowth of residual micrometastases is unknown. We used a highly standardized mouse model of partial hepatic I/R to study the effects of I/R on the outgrowth of preestablished colorectal micrometastases. Five days following intrasplenic injection of C26 colon carcinoma cells, the vascular structures of the left lobe were clamped for 45 minutes under hemodynamically stable conditions. Tissue glutathione, plasma liver enzymes, hepatocellular necrosis, and tumor growth were assessed over time. I/R caused oxidative stress and early liver tissue damage. The outgrowth of micrometastases in occluded liver lobes was accelerated five-to sixfold compared with nonoccluded lobes and was associated with areas of necrotic liver tissue surrounded by inflammatory cells and apoptotic hepatocytes. Accelerated tumor growth and tissue necrosis were completely prevented by occluding blood flow intermittently. In contrast, ischemic preconditioning or treatment with the antioxidants ␣-tocopherol or ascorbic acid failed to protect against late tissue necrosis and tumor growth, although early hepatocellular damage was largely prevented by these methods. In conclusion, I/R is a strong stimulus of recurrent intrahepatic tumor growth. Measures to prevent I/R-induced late tissue necrosis cross-protect against this phenomenon. (HEPATOLOGY 2005;42:165-175.)

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“…The intestinal mucosal atrophy also may be the result of high NO levels. Recent reports [52][53][54] suggest a wide range of intramuscular dose administration schemes for ␣ -tocopherol (up to 500 mg/kg), but in a Medline search, we could not fi nd any dose-dependent toxicity of ␣ -tocopherol. Therefore, the cytoprotective-antioxidant dose of ␣ -tocopherol is yet to be defi ned.…”

Section: Discussionmentioning

confidence: 83%

Does Pharmaconutrition with <i>L</i>-Arginine and/or α-Tocopherol Improve the Gut Barrier in Bile Duct Ligated Rats?

Tuncyurek

Sarı²,

Fırat³

et al. 2006

Eur Surg Res

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Background/Aim: Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and α-tocopherol supplementation in bile duct ligated rats. Methods: Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administerd α-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) α-tocopherol. Nitric oxide, malondialdehyde, and α-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. Results: The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood α-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. Conclusions: An obvious effect of α-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or α-tocopherol supplementation did not seem to improve the gut barrier in our model.

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Intramuscular Administration of Very High Dose of a‐Tocopherol Protects Liver from Severe Ischemia/Reperfusion Injury

Cited by 49 publications

References 24 publications

Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats

Ischemia/reperfusion accelerates the outgrowth of hepatic micrometastases in a highly standardized murine model

Does Pharmaconutrition with <i>L</i>-Arginine and/or α-Tocopherol Improve the Gut Barrier in Bile Duct Ligated Rats?

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