共查询到20条相似文献,搜索用时 31 毫秒
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Sida Niu Feng Li Dun‐Xian Tan Lirong Zhang Jeffrey R. Idle Frank J. Gonzalez Xiaochao Ma 《Journal of pineal research》2010,49(2):106-114
Abstract: The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) and N1‐acetyl‐5‐methoxy‐kynuramine (AMK). The physiological or pathological significance of AFMK/AMK formation during the process of melatonin metabolism in mammals has not been clarified. Using a metabolomic approach in the current study, the AFMK/AMK pathway was thoroughly investigated both in mice and humans. Unexpectedly, AFMK and AMK were not identified in the urine of humans nor in the urine, feces or tissues (including liver, brain, and eyes) in mice under the current experimental conditions. Metabolomic analysis did identify novel metabolites of AMK, i.e. hydroxy‐AMK and glucuronide‐conjugated hydroxy‐AMK. These two newly identified metabolites were, however, not found in the urine of humans. In addition, oxidative stress induced by acetaminophen in the mouse model did not boost AFMK/AMK formation. These data suggest that AFMK/AMK formation is not a significant pathway of melatonin disposition in mice, even under conditions of oxidative stress. 相似文献
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Protective effects of 2,3,5,4‐tetrahydroxystilbene‐2‐o‐β‐D‐glucoside against osteoporosis: Current knowledge and proposed mechanisms 下载免费PDF全文
Jinkang Zhang Songlin Li Linlan Wei Ye Peng Ziyang Zheng Jing Xue Yukun Cao Bin Wang Junjie Du 《International journal of rheumatic diseases》2018,21(8):1504-1513
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Aim: Genipin is reported to stimulate the insertion of multidrug resistance protein 2 (Mrp2) in the bile canalicular membrane, thereby causing choleresis by the increased the biliary excretion of glutathione, which has been considered to be a substrate of Mrp2. In the present study, we examined the effect of genipin on cholestasis induced by estradiol‐17β‐glucuronide and lithocholate‐3‐O‐glucuronide, Mrp2 substrates, in rats. Further, the effect of genipin on the biliary excretion of substrates of P‐glycoprotein (P‐gp), vinblastine and erythromycin, was also studied. Methods: The effect of genipin infusion at the rate of 0.5 µmol/min/100 g on cholestasis induced by estradiol‐17β‐glucuronide (0.075 µmol/min/100 g for 20 min) and lithocholate‐3‐O‐glucuronide (0.15 µmol/min/100 g for 40 min) was studied. The effect of genipin infusion on the biliary excretion of a tracer dose of vinblastine and erythromycin infused at the rate of 0.1 µmol/min/100 g was also studied. Results: Genipin relieved estradiol‐17β‐glucuronide‐induced cholestasis, and cumulative biliary estradiol‐17β‐glucuronide excretion for 120 min was increased from 50 ± 20%–81 ± 20% dose. In contrast, genipin had no effect on lithocholate‐3‐O‐glucuronide‐induced cholestasis. Biliary excretion of a tracer dose of vinblastine and the maximum biliary excretion of erythromycin were significantly decreased by genipin. Conclusions: Genipin protected estradiol‐17β‐glucuronide‐induced cholestasis. The mechanism of the protection of cholestasis by genipin is unknown, but it is speculated to be due to a conformational change of P‐gp by genipin, in addition to the stimulation of Mrp2 insertion into the bile canaliculi. 相似文献
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Melatonin attenuates (‐)‐epigallocatehin‐3‐gallate‐triggered hepatotoxicity without compromising its downregulation of hepatic gluconeogenic and lipogenic genes in mice 下载免费PDF全文
Dongxu Wang Yaqing Wei Taotao Wang Xiaochun Wan Chung S. Yang Russel J. Reiter Jinsong Zhang 《Journal of pineal research》2015,59(4):497-507
(‐)‐Epigallocatehin‐3‐gallate (EGCG), a major constituent of green tea, can ameliorate metabolic syndrome at least in part through reducing gluconeogenesis and lipogenesis. Green tea extracts, of which EGCG is a key constituent, have been used for weight loss in humans. A potential adverse effect of high‐dose EGCG or green tea extracts is hepatotoxicity. Melatonin, an endogenous antioxidant with a high safety profile, is effective in preventing various types of tissue damage. The current study investigated the influence of melatonin on EGCG‐triggered hepatotoxicity and EGCG‐downregulated hepatic genes responsible for gluconeogenesis and lipogenesis in mice. We found that (i) melatonin extended survival time of mice intoxicated with lethal doses of EGCG; (ii) melatonin ameliorated acute liver damage and associated hepatic Nrf2 suppression caused by a nonlethal toxic dose of EGCG; (iii) melatonin reduced subacute liver injury and hepatic Nrf2 activation caused by lower toxic doses of EGCG; and (iv) melatonin did not compromise the action of pharmacological doses of EGCG in downregulating a battery of hepatic genes responsible for gluconeogenesis and lipogenesis, including G6Pc, PEPCK, FOXO1α, SCD1, Fasn, leptin, ACCα, ACCβ, GAPT, and Srebp‐1. Taken together, these results suggest that the combination of EGCG and melatonin is an effective approach for preventing potential adverse effects of EGCG as a dietary supplement for metabolic syndrome alleviation and body weight reduction. 相似文献
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Melatonin enhances L‐DOPA therapeutic effects,helps to reduce its dose,and protects dopaminergic neurons in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced parkinsonism in mice 下载免费PDF全文
Amit Naskar Debashis Dutta Kochupurackal P. Mohanakumar 《Journal of pineal research》2015,58(3):262-274
L‐3,4‐dihydroxyphenylalanine (L‐DOPA) reduces symptoms of Parkinson's disease (PD), but suffers from serious side effects on long‐term use. Melatonin (10–30 mg/kg, 6 doses at 10 hr intervals) was investigated to potentiate L‐DOPA therapeutic effects in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced parkinsonism in mice. Striatal tyrosine hydroxylase (TH) immunoreactivity, TH, and phosphorylated ser 40 TH (p‐TH) protein levels were assayed on 7th day. Nigral TH‐positive neurons stereology was conducted on serial sections 2.8 mm from bregma rostrally to 3.74 mm caudally. MPTP caused 39% and 58% decrease, respectively, in striatal fibers and TH protein levels, but 2.5‐fold increase in p‐TH levels. About 35% TH neurons were lost between 360 and 600 μm from 940 μm of the entire nigra analyzed, but no neurons were lost between 250 μm rostrally and 220 μm caudally. When L‐DOPA in small doses (5–8 mg/kg) failed to affect MPTP‐induced akinesia or catalepsy, co‐administration of melatonin with L‐DOPA attenuated these behaviors. Melatonin administration significantly attenuated MPTP‐induced loss in striatal TH fibers (82%), TH (62%) and p‐TH protein (100%) levels, and nigral neurons (87–100%). Melatonin failed to attenuate MPTP‐induced striatal dopamine depletion. L‐DOPA administration (5 mg/kg, once 40 min prior to sacrifice, p.o.) in MPTP‐ and melatonin‐treated mice caused significant increase in striatal dopamine (31%), as compared to L‐DOPA and MPTP‐treated mice. This was equivalent to 8 mg/kg L‐DOPA administration in parkinsonian mouse. Therefore, prolonged, effective use of L‐DOPA in PD with lesser side effects could be achieved by treating with 60% lower doses of L‐DOPA along with melatonin. 相似文献
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Jun An Guo‐Gang Feng Lei Huang Tsuyoshi Kurokawa Toshiaki Nonami Tatsuro Koide Fumio Kondo Toru Komatsu Koji Tsunekawa Yoshihiro Fujiwara Hidemi Goto Hiroshi Nishikawa Tokutaro Miki Satoru Sugiyama Naohisa Ishikawa 《Hepatology research》2010,40(6):613-621
Aim: The present study was undertaken to evaluate the effects of 1‐O‐hexyl‐2,3,5‐trimethylhydroquinone (HTHQ), a synthesized vitamin E derivative, on carbon tetrachloride (CCl4)‐induced cirrhosis. Methods: Rats were treated with hypodermic injections of CCl4 twice a week to induce the hepatic cirrhosis, and given drinking water containing HTHQ or solvent. Primary cultures of rat hepatocytes were performed to evaluate the effects of HTHQ on the expression of inducible nitric oxide synthase (iNOS). Results: Masson's staining of rat livers showed fibrosis around pseudo‐lobules in the CCl4 group, the lesions being reduced in the CCl4 HTHQ group. Increases in liver tissue hydroxyproline and α1(I) collagen, α‐smooth muscle actin and iNOS induced by CCl4, were also markedly diminished by HTHQ. Furthermore, both HTHQ and vitamin E attenuated interleukin‐1β‐induced iNOS protein expression in cultured hepatocytes, the potency of HTHQ being 10‐times higher than that of vitamin E. Conclusion: HTHQ may inhibit development of hepatic cirrhosis in rats, more potently than vitamin E, by inhibiting the iNOS expression in hepatocytes. Because vitamin E has a radical scavenging action, roles of NO and peroxynitrite will be discussed in the effects of HTHQ on the fibrosis. 相似文献
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Hikaru Iwashita Yukihisa Matsumoto Yusuke Maruyama Kazuki Watanabe Atsuhiko Chiba Atsuhiko Hattori 《Journal of pineal research》2021,70(1):e12703
Melatonin (MEL) has been reported to enhance cognitive processes, making it a potential treatment for cognitive decline. However, the role of MEL’s metabolites, N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) and N1‐acetyl‐5‐methoxykynuramine (AMK), in these effects are unknown. The current study directly investigated the acute effects of systemic MEL, AFMK, and AMK on novel object recognition. We also analyzed MEL, AFMK, and AMK levels in hippocampus and temporal lobe containing the perirhinal cortex following systemic MEL and AMK treatment. AMK administered post‐training had a more potent effect on object memory than MEL and AFMK. AMK was also able to rescue age‐associated declines in memory impairments when object memory was tested up to 4 days following training. Results from administering AMK at varying times around the training trial and the metabolism time course in brain tissue suggest that AMK’s memory‐enhancing effects reflect memory consolidation. Furthermore, inhibiting the MEL‐to‐AMK metabolic pathway disrupted object memory at 24 hours post‐training, suggesting that endogenous AMK might play an important role in long‐term memory formation. This is the first study to report that AMK facilitates long‐term object memory performance in mice, and that MEL crosses the blood‐brain barrier and is immediately converted to AMK in brain tissue. Overall, these results support AMK as a potential therapeutic agent to improve or prevent memory decline. 相似文献
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Miho Ichiba Yoshiko Maeta Tomoyuki Mukoyama Toshiya Saeki Sakiko Yasui Takamasa Kanbe Jun‐Ichi Okano Yoshinao Tanabe Yasuaki Hirooka Sadako Yamada Akihiro Kurimasa Yoshikazu Murawaki Goshi Shiota 《Liver international》2003,23(5):338-345
Abstract: Reactive oxygen species may be involved in the progression of chronic liver disease and the occurrence of hepatocellular carcinoma (HCC). To clarify whether clinicopathological findings in liver diseases are related to oxidative DNA damage, hepatic expression of the 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) was examined in 75 liver disease patients, which included 32 chronic hepatitis (CH), 13 liver cirrhosis (LC) and 30 HCC patients. The CH patients had higher 8‐OHdG‐positive hepatocytes than LC (P<0.05). In CH and LC, the number of 8‐OHdG‐positive hepatocytes was correlated with alanine aminotransferase and asparate aminotransferase (P<0.01 and P<0.05, respectively). Of 30 HCC cases, 25 cases (83%) showed stronger immunoreactivity than non‐cancerous counterparts. The patients with poorly differentiated HCC had a larger tumor size and higher levels of AFP, and exhibited higher labeling indices of PCNA‐, TUNEL‐ and 8‐OHdG‐positive cells than those with well and moderately differentiated HCC. Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic liver disease and determination of 8‐OHdG is useful in assessing high‐grade malignancy in HCC. 相似文献
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A Novel and Selective Nociceptin Receptor (NOP) Agonist (1‐(1‐((cis)‐4‐isopropylcyclohexyl)piperidin‐4‐yl)‐1H‐indol‐2‐yl)methanol (AT‐312) Decreases Acquisition of Ethanol‐Induced Conditioned Place Preference in Mice 下载免费PDF全文
Nurulain T. Zaveri Paul V. Marquez Michael E. Meyer Willma E. Polgar Abdul Hamid Kabirullah Lutfy 《Alcoholism, clinical and experimental research》2018,42(2):461-471
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Rajiv Gupta Sunil Kumar Peter Gow Leon Chang Linda Yen 《Internal medicine journal》2020,50(4):484-487
Anti‐MDA5‐associated dermatomyositis (MDA5‐associated DM) is an uncommon presentation of idiopathic inflammatory myositis, typically amyopathic, associated with rapidly progressive, treatment refractory interstitial lung disease and poor prognosis, particularly in patients with concomitant rapidly progressive interstitial lung disease (RP‐ILD). We report two cases of MDA5‐associated DM with fatal outcome in one of the patients, despite ‘aggressive triple therapy’ for RP‐ILD. 相似文献
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Impact of serum Wisteria floribunda agglutinin positive Mac‐2‐binding protein and serum interferon‐γ‐inducible protein‐10 in primary biliary cirrhosis 下载免费PDF全文
Hiroki Nishikawa Hirayuki Enomoto Yoshinori Iwata Kunihiro Hasegawa Chikage Nakano Ryo Takata Takashi Nishimura Kazunori Yoh Nobuhiro Aizawa Yoshiyuki Sakai Naoto Ikeda Tomoyuki Takashima Akio Ishii Hiroko Iijima Shuhei Nishiguchi 《Hepatology research》2016,46(6):575-583
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Clinical significance of half‐lives of tumor markers α‐fetoprotein and des‐γ‐carboxy prothrombin after hepatectomy for hepatocellular carcinoma 下载免费PDF全文
Masayo Tsukamoto Hidetoshi Nitta Katsunori Imai Takaaki Higashi Shigeki Nakagawa Hirohisa Okabe Kota Arima Takayoshi Kaida Katsunobu Taki Daisuke Hashimoto Akira Chikamoto Takatoshi Ishiko Toru Beppu Hideo Baba 《Hepatology research》2018,48(3):E183-E193
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The prognostic significance of the half‐lives (HLs) of α‐fetoprotein (AFP) and des‐γ‐carboxy prothrombin (DCP) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) is unclear. We evaluated the HLs of AFP and DCP in a cohort of such patients.Methods
This study included data on 202 patients with HCC who underwent curative hepatectomy and had preoperative AFP concentrations ≥100 ng/mL or DCP ≥200 mAU/mL. We calculated the HLs of AFP and DCP from their values just before and 1 month after hepatectomy. We identified three groups: a normalization group, tumor marker concentrations within normal range 1 month post‐hepatectomy; a long group, HL of AFP ≥7 days or DCP ≥4 days; and a short group, remaining patients. We evaluated associations between HL and prognosis.Results
Three‐year recurrence‐free survival (RFS) in the normalization (n = 70), short (n = 71), and long groups (n = 61) was 41.3%, 46.0%, and 16.8%, respectively (P = 0.002). Five‐year overall survival (OS) of normalization, short, and long groups was 72.6, 70.6 and 43.8%, respectively (P = 0.002). Multivariate analysis revealed that long HL is an independent risk factor for poor RFS (hazard ratio [HR] 2.21, P = 0.0006) and poor OS (HR 2.70, P = 0.004). The extrahepatic recurrence rate was 21.3% (13/61) in the long group, which is higher than in the normalization group (8.6%, 6/70) (P = 0.04) and short group (9.9%, 7/71) (P = 0.07).Conclusion
Post‐hepatectomy HLs of AFP and DCP are predictors of long‐term outcome in patients with HCC. 相似文献19.
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Orazio Palmieri Antonio M. Ippolito Maurizio Margaglione Maria R. Valvano Domenica Gioffreda Massimo Fasano Giovanna D'Andrea Giuseppe Corritore Michele Milella Nicola Andriulli Filomena Morisco Lydia Giannitrapani Anna Latiano Rosanna Fontana Pietro Gatti Paolo Tundo Michele Barone Raffaele Cozzolongo Teresa Santantonio Angelo Andriulli 《Liver international》2014,34(9):1369-1377