Mechanisms of Protection by S-Allylmercaptocysteine Against Acetaminophen-Induced Liver Injury in Mice

Sumioka, Isao; Matsura, Tatsuya; Kasuga, Shigeo; Itakura, Y.; Yamada, Kazuo

doi:10.1254/jjp.78.199

Cited by 39 publications

(29 citation statements)

References 39 publications

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“…These characteristic components are not contained in the raw garlic, and are made from gamma-glutamyl-SAC (GSAC), gamma-glutamyl-SMC (GSMC), alliin or methiin after extracted/aged on raw garlic for a long period. They have been reported to possess anti-oxidative [14][15][16], cancer preventive [17][18][19] and hepatoprotective properties [20]. The anti-fatigue effect of garlic differs according to the processing method employed, and it has been demonstrated that AGE is one of the processed products that has the most desirable effects [21,22].…”

Section: Garlicmentioning

confidence: 99%

Garlic as an anti‐fatigue agent

Morihara¹,

Nishihama

Ushijima

et al. 2007

Molecular Nutrition Food Res

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More than three thousand publications in the past have confirmed the efficacy of garlic for the prevention and treatment of a variety of diseases, acknowledging and validating its traditional uses. Garlic is also used for the treatment of fatigue, although the mechanism involved remain unclear. The anti-fatigue function of garlic may be closely related to its many favorable biological and pharmacological effects. In animal studies, garlic has been shown to promote exercise endurance. Differences in the methods of processing garlic result in differences in the intensity of its anti-fatigue effect, and the most favorable form of processing has been shown to be extraction of raw garlic followed by its natural aging for a long period in a water-ethanol mixture. In human studies, it has been confirmed that garlic produces symptomatic improvement in persons with physical fatigue, systemic fatigue due to cold, or lassitude of indefinite cause, suggesting that garlic can resolve fatigue through a variety of actions. Recently, primarily in Japan, attempts have been made to measure the intensity of fatigue objectively and quantitatively using biomarkers. Currently available data strongly suggest that garlic may be a promising anti-fatigue agent, and that further studies to elucidate its application are warranted.

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Section: Garlicmentioning

confidence: 99%

Garlic as an anti‐fatigue agent

Morihara¹,

Nishihama

Ushijima

et al. 2007

Molecular Nutrition Food Res

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“…Specifically, we studied liver and kidney because garlic compounds undergo hepatic metabolism and are excreted in the urine (15), and we assessed the stomach epithelium due to its direct exposure to concentrated S-allylmercaptocysteine. In fact, previous animal studies showed that 200 mg/kg S-allylmercaptocysteine actually protected against toxin-induced liver damage, with similar efficacy to human hepatoprotective drug N-acetylcysteine (27). It is noteworthy that N-acetylcysteine has a similar cysteinebased chemical structure to S-allylmercaptocysteine and is administered routinely to humans in oral doses of 540 mg/kg/ d, supporting the clinical relevance of the 300 mg/kg/d S-allylmercaptocysteine dose we administered to our mice.…”

Section: Discussionmentioning

confidence: 94%

“…To exclude serious toxicity, we screened for the presence of organ pathology in S-allylmercaptocysteine -treated mice using a 50% higher dose (300 mg/kg/d) than the maximum previously described (27). After treating for 30 days, no anatomic abnormalities or signs of inflammation, necrosis, or hemorrhage were observed at postmortem evaluations.…”

Section: Resultsmentioning

confidence: 99%

Garlic-DerivedS-allylmercaptocysteine Is a NovelIn vivoAntimetastatic Agent for Androgen-Independent Prostate Cancer

Howard

Ling

Chua

et al. 2007

Clinical Cancer Research

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Purpose: There is epidemiologic evidence that high garlic consumption decreases the incidence of prostate cancer, and compounds isolated from garlic have been shown to have cancer-preventive and tumor-suppressive effects. Recent in vitro studies in our laboratory have shown that garlic-derived organosulfur compound S-allylmercaptocysteine suppresses invasion and cell motility of androgen-independent prostate cancer cells via the up-regulation of celladhesion molecule E-cadherin. S-allylmercaptocysteine is therefore a potential antimetastatic drug with broad clinical applications that we tested in vivo for the first time in this study. Experimental Design: We used a newly established fluorescent orthotopic androgenindependent prostate cancer mouse model to assess the ability of S-allylmercaptocysteine to inhibit tumor growth and dissemination. Results: We showed that oral S-allylmercaptocysteine not only inhibited the growth of primary tumors by up to 71% (P < 0.001) but also reduced the number of lung and adrenal metastases by as much as 85.5% (P = 0.001) without causing notable toxicity. This metastatic suppression was accompanied by a 91% reduction of viable circulating tumor cells (P = 0.041), suggesting that S-allylmercaptocysteine prevents dissemination by decreasing tumor cell intravasation. Conclusions: Our results provide in vivo evidence supporting the potential use of S-allylmercaptocysteine as an E-cadherin up-regulating antimetastatic agent for the treatment of androgen-independent prostate cancer. This is the first report of the in vivo antimetastatic properties of garlic, which may also apply to other cancer types.Prostate cancer is the second most frequent cause of male cancer death in the United States (1). Despite the widespread presence of clinically insignificant tumors in elderly men, prostate cancer commonly has an aggressive phenotype that requires prompt intervention (2). For metastatic disease, the initial medical treatment is androgen deprivation, which induces tumor regression and reduction in serum prostatespecific antigen in 80% to 85% of cases. Unfortunately, androgen-independent tumor recurrence is almost ubiquitous, for which only palliative treatment is available, and even the newest docetaxel-based regimes confer only a 2.4-month survival advantage (3). Death from prostate cancer is the result of metastatic spread, characteristically to the bones, lungs, liver, pleura, and adrenals (4). Bony metastasis is characterized by severe chronic pain, spinal cord compression, and pathologic fractures. Prostate cancer is therefore a highly desirable target for effective and tolerable antimetastatic drugs.Certain dietary agents may have a preventive effect for prostate cancer, including tomato-derived lycopene, vitamin E, and selenium (5). Furthermore, epidemiologic evidence supports a protective role for high garlic consumption, with one study indicating that high garlic consumption (>10 g/d) was related to low prostate cancer prevalence in China (relative risk, 0.51; P < 0.001; r...

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“…A relatively lower degree of hepatic damage in the CoQ10 group is indicative of the hepatoprotective nature of CoQ10. While there is no direct evidence of the hepatoprotective effect of CoQ10, it has been reported that maintenance of the normal level of CoQ9H2 in the S-allylmercaptocysteine pretreatment group may suppress acetaminophen-induced liver injury (Sumioka et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Effect of CoQ10 on N-nitrosodiethylamine-induced Oxidative Stress in Mice

Song

Kim

Park

et al. 2009

Korean J Physiol Pharmacol

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The antioxidant effect of CoQ10 on N-nitrosodiethylamine (NDEA)-induced oxidative stress was investigated in mice. Food intake and body weight were similar in both CoQ10 and control groups during the 3-week experimental period. NDEA significantly increased the activities of typical marker enzymes of liver function (AST, ALT and ALP) both in control and CoQ10 groups. However, the increase of plasma aminotransferase activity was significantly reduced in the CoQ10 group. Lipid peroxidation in various tissues, such as heart, lung, liver, kidney, spleen and plasma, was significantly increased by NDEA, but this increase was significantly reduced by 100 mg/kg of CoQ10. Superoxide dismutase activity increased significantly upon NDEA-induced oxidative stress in both the control and CoQ10 groups with the effect being less in the CoQ10 group. Catalase activity decreased significantly in both the control and CoQ10 groups treated with NDEA, again with the effect being less in the CoQ10 group. The lesser effect on superoxide dismutase and catalase in the NDEA-treated CoQ10 group is indicative of the protective effect CoQ10. Thus, CoQ10 can offer useful protection against NDEA-induced oxidative stress.

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Mechanisms of Protection by S-Allylmercaptocysteine Against Acetaminophen-Induced Liver Injury in Mice

Cited by 39 publications

References 39 publications

Garlic as an anti‐fatigue agent

Garlic as an anti‐fatigue agent

Garlic-DerivedS-allylmercaptocysteine Is a NovelIn vivoAntimetastatic Agent for Androgen-Independent Prostate Cancer

Antioxidant Effect of CoQ10 on N-nitrosodiethylamine-induced Oxidative Stress in Mice

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