Chemopreventive doses of resveratrol do not produce cardiotoxicity in a rodent model of hepatocellular carcinoma.
*Chemoprevention; Analysis of Variance; Animal; Animal Studies; Animal/drug effects; Animals; Antioxidants; Behavior; Blotting; Carcinoma; Cardiotoxicity; Cardiotoxins/*toxicity; Chemoprevention; Data Analysis Software; Descriptive Statistics; Disease Models; Doppler; Dose-Response Relationship; Drug; Echocardiography; Feeding Behavior/drug effects; Female; Fisher's Exact Test; Funding Source; Heart – Drug Effects; Heart/drug effects/physiopathology; Hepatocellular – Prevention and Control; Hepatocellular/*drug therapy/pathology/physiopathology; Hepatocytes/drug effects/pathology; Humans; Liver Neoplasms/*drug therapy/pathology/physiopathology; Liver/drug effects/pathology/physiopathology; Polyphenols – Therapeutic Use; Rats; Resveratrol; Sprague-Dawley; Stilbenes/*therapeutic use; Systole/drug effects; Western
Hepatocellular carcinoma (HCC), one of the most lethal cancers, results in more than one million fatalities worldwide every year. In view of the limited therapeutic alternatives and poor prognosis of liver cancer, preventive control approaches, notably chemoprevention, have been considered to be the best strategy in lowering the present prevalence of the disease. Resveratrol, a naturally occurring antioxidant and antiinflammatory agent found in grapes and red wine, inhibits carcinogenesis with a pleiotropic mode of action. Recently, we have reported that dietary resveratrol significantly prevents chemically-induced liver tumorigenesis in rats. One of the mechanisms of resveratrol-mediated chemoprevention of hepatocarcinogenesis could be related to its antiinflammatory action through hepatic cyclooxygenase (COX-2) inhibition. Although several COX-2 inhibitors are known to exert chemopreventive efficacy, not all are considered ideal candidates for chemoprevention due to the risk of adverse cardiovascular events. Accordingly, the objective of the present study was to evaluate the role of resveratrol on cardiac performance during experimental hepatocarcinogenesis initiated with diethylnitrosamine and promoted by phenobarbital. Rats had free access to diet supplemented with resveratrol four weeks before the carcinogen injection and 14 weeks thereafter. The cardiotoxicity of resveratrol was assessed by monitoring the cardiac function using transthoracic echocardiography as well as Western blot analysis of cardiac tissue. Long-term dietary administration of resveratrol dose-dependently suppressed hepatic tumor multiplicity, the principal endpoint for evaluating the chemopreventive potential of a candidate agent. The chemopreventive effects of resveratrol were also reflected in histopathological assessment of hepatic tissues. Resveratrol did not exhibit any cardiotoxicity but rather improved the cardiac function in a dose-responsive fashion. Our results indicate that resveratrol-mediated chemoprevention of rat liver carcinogenesis is devoid of any adverse cardiovascular events. Resveratrol may be developed as a chemopreventive as well as therapeutic drug for human HCC.
Luther Daniel J; Ohanyan Vahagn; Shamhart Patricia E; Hodnichak Cheryl M; Sisakian Hamayak; Booth Tristan D; Meszaros J Gary; Bishayee Anupam
Investigational new drugs
2011
2011-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s10637-009-9332-7" target="_blank" rel="noreferrer noopener">10.1007/s10637-009-9332-7</a>
The health benefits of blackcurrants.
*Health Promotion; *Ribes/chemistry; Anthocyanins/analysis; Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Fatty Acids; Flavonoids/analysis; Fruit/chemistry; Humans; Phytogenic; Phytotherapy; Plant Extracts/adverse effects/pharmacokinetics/pharmacology; Unsaturated/analysis
The blackcurrant (Ribes nigrum L., Grossulariceae), a small, perennial shrub native to central Europe and northern Asia, is cultivated throughout the world, including the United States. In addition to its anecdotal use in traditional herbal medicine, modern laboratories have demonstrated the potent anti-inflammatory, antioxidant and antimicrobial effects of blackcurrant constituents on a myriad of disease states. The properties of the blackcurrants are conferred from its biochemical constituents, some of which include anthocyans (specifically delphinidin-3-O-glucoside, delphinidin-3-O-rutinoside, cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside), flavonols, phenolic acids and polyunsaturated fatty acids. A plethora of studies have been published with regards to its various therapeutic applications. This article attempts to summarize these studies, providing a general overview of the research in this field. Several studies focus on the therapeutic potential of blackcurrants with regards to hypertension and other cardiovascular-associated illnesses, neoplastic, neurodegenerative and ocular diseases, nephrolithiasis, and diabetic neuropathy. Safety concerns and future directions are also mentioned, suggesting the critical examination of the exact mechanism of action, specific radical-scavenging capabilities of the blackcurrants and the crucial need for well-designed clinical trials to ensure the successful use of blackcurrants in a clinical setting.
Gopalan Ashwin; Reuben Sharon C; Ahmed Shamima; Darvesh Altaf S; Hohmann Judit; Bishayee Anupam
Food & function
2012
2012-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1039/c2fo30058c" target="_blank" rel="noreferrer noopener">10.1039/c2fo30058c</a>
Chemopreventive and therapeutic potential of tea polyphenols in hepatocellular cancer.
*Anticarcinogenic Agents; Animal; Animals; Anti-Inflammatory Agents; Antioxidants; Biological Availability; Biological Markers; Carcinoma; Catechin/administration & dosage/analogs & derivatives; Chemoprevention; Disease Models; Hepatocellular – Physiopathology; Hepatocellular – Prevention and Control; Hepatocellular – Therapy; Human; Humans; In Vitro Studies; In Vivo Studies; Liver Neoplasms/*drug therapy/*prevention & control; Mice; Neoplasms – Prevention and Control; Nutrition; Outcomes (Health Care); Phenols – Therapeutic Use; Polyphenols/*administration & dosage/pharmacology; Tea – Therapeutic Use; Tea/*chemistry; Xenograft Model Antitumor Assays
The prophylactic and therapeutic properties of tea have been attributed to green tea catechins and black tea theaflavins besides several other polyphenolic compounds. Tea polyphenols possess potent antioxidant and antiinflammatory properties and modulate several signaling pathways. These biochemical facets of tea polyphenols are responsible for its anticancer properties. Several lethal cancers, such as liver cancer, develop within a background of oxidative stress and inflammation. Liver cancer, also known as hepatocellular carcinoma (HCC), has been shown to occur throughout the world including Asia, Africa, Western Europe, and the United States. Phytochemicals, such as tea polyphenols, provide an effective and promising alternative for the chemoprevention and treatment of HCC. In this article, we systematically review, for the first time, the effects of tea polyphenols in the preclinical in vitro and in vivo HCC models. The review also examines, in critical detail, the biochemical mechanisms involved in the chemopreventive and antineoplastic effects of tea polyphenols in hepatic cancer. Finally, we highlight the role of synergy, bioavailability and pharmacokinetics of tea polyphenols, current status of clinical trials, discuss future directions, and comment on the future challenges involved in the effective use of tea polyphenols for the prevention and management of liver cancer.
Darvesh Altaf S; Bishayee Anupam
Nutrition and cancer
2013
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1080/01635581.2013.767367" target="_blank" rel="noreferrer noopener">10.1080/01635581.2013.767367</a>
Pharmacotherapy of Alzheimer's disease: current and future trends.
Humans; Alzheimer's disease; Alzheimer Disease/*drug therapy; anti-inflammatory agents; antioxidants; cholinesterase inhibitors; dementia; Drug Therapy/*methods/*trends; immunotherapy; memantine; multi-targeted drugs; natural products; pharmacotherapy
Alzheimer's disease (AD) and its related dementia has shown an alarming rise in the global population. Although considerable efforts have been made to develop effective therapeutic agents for AD therapy, drug development has not met significant clinical success. Current pharmacotherapy of AD is limited to cholinesterase inhibitors and the N-methyl-D-aspartate antagonist memantine. Considerable research is underway to develop newer agents for the management of AD. Since amyloid-beta (Abeta) has been implicated in AD pathogenesis, the use of beta secretase inhibitors as well as immunotherapy against Abeta has been investigated. A considerable effort has been spent investigating the therapeutic potential of antioxidants and anti-inflammatory agents, several of natural products and dietary origin, in AD treatment. Numerous drug targets have also been investigated for AD treatment and a modest drug pipeline is available. Despite these efforts, drug development for AD has proved extremely difficult and most clinical trials have afforded disappointing results.
Geldenhuys Werner J; Darvesh Altaf S
Expert review of neurotherapeutics
2015
2015-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1586/14737175.2015.990884" target="_blank" rel="noreferrer noopener">10.1586/14737175.2015.990884</a>
Mechanical Ventilation Antioxidant Trial.
Adult; Female; Humans; Male; Middle Aged; Time Factors; Aged; Length of Stay; Treatment Outcome; Prospective Studies; Oxidative Stress; Double-Blind Method; Intensive Care Units; Antioxidants/*therapeutic use; Antioxidants; Oxidative Stress/*drug effects; Critical Care/*methods; Human; Chi Square Test; Funding Source; Data Analysis Software; Middle Age; T-Tests; Ascorbic Acid/therapeutic use; Critical Illness; Cystine/analogs & derivatives/therapeutic use; Inflammation/*drug therapy/*etiology; Vitamin E/therapeutic use; Vitamins/therapeutic use; 80 and over; Artificial; Respiration; Artificial/*adverse effects; Randomized Controlled Trials; Double-Blind Studies; Acetylcysteine; Critically Ill Patients; Dietary Supplementation; Log-Rank Test; Mantel-Haenszel Test; Ventilator Weaning; Vitamin E; 80 and Over; Ascorbic Acid – Administration and Dosage
BACKGROUND: Many patients each year require prolonged mechanical ventilation. Inflammatory processes may prevent successful weaning, and evidence indicates that mechanical ventilation induces oxidative stress in the diaphragm, resulting in atrophy and contractile dysfunction of diaphragmatic myofibers. Antioxidant supplementation might mitigate the harmful effects of the oxidative stress induced by mechanical ventilation. OBJECTIVE: To test the clinical effectiveness of antioxidant supplementation in reducing the duration of mechanical ventilation. METHODS: A randomized, prospective, placebo-controlled double-blind design was used to test whether enterally administered antioxidant supplementation would decrease the duration of mechanical ventilation, all-cause mortality, and length of stay in the intensive care unit and hospital. Patients received vitamin C 1000 mg plus vitamin E 1000 IU, vitamin C 1000 mg plus vitamin E 1000 IU plus N-acetylcysteine 400 mg, or placebo solution as a bolus injection via their enteral feeding tube every 8 hours. RESULTS: Clinical and statistically significant differences in duration of mechanical ventilation were seen among the 3 groups (Mantel-Cox log rank statistic = 5.69, df = 1, P = .017). The 3 groups did not differ significantly in all-cause mortality during hospitalization or in the length of stay in the intensive care unit or hospital. CONCLUSIONS: Enteral administration of antioxidants is a simple, safe, inexpensive, and effective intervention that decreases the duration of mechanical ventilation in critically ill adults.
Howe Kimberly P; Clochesy John M; Goldstein Lawrence S; Owen Hugh
American journal of critical care : an official publication, American Association of Critical-Care Nurses
2015
2015-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.4037/ajcc2015335" target="_blank" rel="noreferrer noopener">10.4037/ajcc2015335</a>