Resolution of Liver Fibrosis in Chronic CCl4 Administration in the Rat after Discontinuation of Treatment: Effect of Silymarin, Silibinin, Colchicine and Trimethylcolchicinic Acid

Q3 · MEDICINE

Article

Author: Moreno, Mario G. ; Hernandez, Maria del C. ; Chavez, Enrique ; Muriel, Pablo ; Alcantar, Lidia K.

The aim of the present study was to investigate the hypothesis that liver tissue repair induced by exposure to chloroform (CHCl(3))+trichloroethylene binary mixture (BM) is dose-dependent similar to that elicited by exposure to these compounds individually. Male Sprague-Dawley rats (250-300 g) received three dose combinations of binary mixture (74+250, 185+500 and 370+1250 mg CHCl(3)+trichloroethylene/kg, intraperitoneally) in corn oil (maximum of 0.5 ml/kg). Liver injury was assessed by plasma alanine amino transaminase (ALT) activity and histopathology by haematoxylin & eosin. Liver tissue repair was measured by (3)H-thymidine incorporation into hepatonuclear DNA. Blood and liver levels of both the parent compounds and two major metabolites of trichloroethylene (trichloroacetic acid and trichloroethanol) were quantified by gas chromatography. The blood and liver CHCl(3) levels after the administration of binary mixture were similar compared to the administration of CHCl(3) alone. The blood and liver trichloroethylene levels after the binary mixture were significantly lower compared to trichloroethylene alone due to higher elimination in presence of CHCl(3), resulting in decreased production of metabolites. The antagonistic toxicokinetics resulted in lower liver injury than the summation of injury caused by the individual components at all three dose levels. On the other hand, tissue repair elicited by the binary mixture was dose-dependent. The interactive toxicity of this binary mixture of CHCl(3) and trichloroethylene led to subadditive initial liver injury because of a combined effect of higher elimination of TCE and mitigated progression of liver injury was prevented by timely dose-dependent stimulation of compensatory tissue repair. Even though the doses of the toxicants employed in this study are much higher than found in the environment, the results suggest that a mixture of these two compounds at environmental levels is unlikely to cause any exaggerated interactive acute liver toxicity of any biological significance.

01 Feb 2005·Free Radical ResearchQ3 · BIOLOGY

Protection by tropolones against H₂O₂-induced DNA damage and apoptosis in cultured Jurkat cells

Q3 · BIOLOGY

Article

Author: Galaris, Dimitrios ; Nousis, Lambros ; Zhu, Ben-Zhan ; Doulias, Paschalis-Thomas ; Frei, Balz

Tropolones, the naturally occurring compounds responsible for the durability of heartwood of several cupressaceous trees, have been shown to possess both metal chelating and antioxidant properties. However, little is known about the ability of tropolone and its derivatives to protect cultured cells from oxidative stress-mediated damage. In this study, the effect of tropolones on hydrogen peroxide-induced DNA damage and apoptosis was investigated in cultured Jurkat cells. Tropolone, added to the cells 15 min before the addition of glucose oxidase, provided a dose dependent protection against hydrogen peroxide induced DNA damage. The IC50 value observed was about 15 microM for tropolone. Similar dose dependent protection was also observed with three other tropolone derivatives such as trimethylcolchicinic acid, purpurogallin and beta-thujaplicin (the IC50 values were 34, 70 and 74 microM, respectively), but not with colchicine and tetramethyl purpurogallin ester. Hydrogen peroxide-induced apoptosis was also inhibited by tropolone. However, in the absence of exogenous H2O2 but in the presence of non-toxic concentrations of exogenous iron (100 microM Fe3+), tropolone dramatically increased the formation of single strand breaks at molar ratios of tropolone to iron lower than 3 to 1, while, when the ratio increased over 3, no toxicity was observed. In conclusion, the results presented in this study indicate that the protection offered by tropolone against hydrogen peroxide-induced DNA damage and apoptosis was due to formation of a redox-inactive iron complex, while its enhancement of iron-mediated DNA damage at ratios of [tropolone]/[Fe3+] lower than 3, was due to formation of a lipophilic iron complex which facilitates iron transport through cell membrane in a redox-active form.

01 May 1997·Journal of Applied ToxicologyQ4 · MEDICINE

Trimethylcolchicinic Acid Decreases Liver Fibrosis and Cholestasis Induced by Prolonged Biliary Obstruction in the Rat

Q4 · MEDICINE

Article

Author: Pablo Muriel ; Pedro U. Ostoa-Saloma ; Jorge A. Reyes-Esparsa ; Lourdes Rodríguez-Fragoso

Colchicine is effective in decreasing hepatic fibrosis. However, several toxic reactions have been reported after colchicine treatment which are attributed to its ability to bind tubulin. The aim of this work is to determine if trimethylcolchicinic acid, which does not bind tubulin, is able to decrease experimental liver fibrosis and cholestasis. In male Wistar rats, the common bile duct was ligated. Administration of trimethylcolchicinic acid (TMCA, 100 micrograms rat-1 day-1, p.o.) began 4 weeks after biliary obstruction and continued for a further 4 weeks. The liver was used for histological and ultrastructural analysis and for collagen quantification (hydroxyproline content). The degradation of Matrigel and collagen (types I and III), as well as plasminogen activator activity, was determined in liver homogenates. Bilirubins and enzyme activities were measured in serum. Trimethylcolchicinic acid was able to improve normal liver histology, ultrastructure, collagen content and biochemical markers of liver damage. It also increased matrigel degradation and plasminogen activator activity. The mechanism of TMCA is probably associated with its ability to increase Matrigel degradation; however, other actions cannot be discarded.

News (Medical) associated with Trimethylcolchicinic acid

29 Nov 2022

·www.prnewswire.com

Atherosclerosis Drugs Market to Benefit from Integration of Nanotechnology to Develop High-Quality Drugs

Drug Manufacturers to Collaborate with Retail Pharmacies; Atherosclerosis Drugs Sales in Retail Pharmacies to Reach US$ 24 Billion by 2027 Fact.MR's latest analysis on atherosclerosis drugs market scrutinizes key growth factors that are impacting sales in the market. The report offers in-depth insights covering vital factors such as drivers, opportunities, key player strategies, and demand outlook for the atherosclerosis drugs market. In addition to this, the study analyzes latest trends across segments including drug class, distribution channel, and region for the forecast period (2020-2027). ROCKVILLE, Md., Nov. 29, 2022 /PRNewswire/ -- A Market Research and Competitive Intelligence Provider: The global atherosclerosis drugs market is expected to witness robust growth over the upcoming decade. Demand in the market is predicted to rise due to growing prevalence of atherosclerosis and cardiovascular diseases across the globe. As per the National Center of Biotechnology Information, around 610,000 Americans succumb to heart disease every year. Out of these, significant portion of these deaths are due to the initial attack of atherosclerosis and is among men above the age of 50 years. Hence, to reduce the global burden of this disease, healthcare professionals and leading companies are developing novel drugs and are integrating nano-technology. Competency of nano polymers is improving the diagnosis and drug delivery system to combat cardiovascular diseases. Further, one such nano-polymer to improve the function of heart muscles is E-selectin-targeting polymer. With increasing number of mortality rates due to heart attack and strokes, the demand for atherosclerosis drugs is expected to surge over the forecast period. Moreover, proliferation of online and retail pharmacies is one of the key factors facilitating the growth in the market. Availability of these drugs in the retail pharmacies at low-cost and presence of these pharmacies at key locations will create conducive environment for the manufacturers. Hence, to expand their customer base and gain revenue, some of the key players are joining hands with hospital and retail pharmacies. Download A Free Sample Copy! Consequently, growing popularity of generic drugs coupled with government initiatives to raise the awareness regarding these diseases will drive the growth in the market. Regionally, North America dominated the market and the trend is likely to continue over the forecast period. However, Asia is expected to gain significant revenue on the back of improved healthcare infrastructure and development of novel drugs across China, Japan, and India. Key Takeaways: By drug class, demand is likely to remain high for cholesterol lowering medications sue to surge in cardiovascular diseases cases. By distribution channel, hospital pharmacies segment is projected to hold around 46% share of the global atherosclerosis drugs market by 2027. The retail pharmacies segment is set to reach a total market valuation of US$ 24 Bn by 2027. North America is projected to account for 34% market share of the global market by 2027. Europe atherosclerosis drugs market is poised to exhibit strong growth during the projection period. With rising penetration of generic drugs and surge in cardiovascular diseases, Asia Pacific is likely to emerge as a lucrative market for atherosclerosis drug through 2027 Growth Drivers: Rising incidence of atherosclerosis and other heart diseases is a key factor driving the global atherosclerosis drugs market. Increasing government initiatives along with growing awareness about atherosclerosis and its treatments will create prospects for the market during the forecast period. Continuous new product launches and approvals is expected to boost the global market through 2027. Restraints: Low diagnostic rates are limiting the expansion of the global atherosclerosis drugs market. Side effects associated with atherosclerosis drugs is also restraining the market growth to some extent. Don't Need a Global Report? Save 40% on Country & Region Specific Reports Competitive Landscape: Leading manufacturers of atherosclerosis drugs are focused on upgrading their product portfolios by means of new product launches and approvals. Besides this, they are investing heavily in research and development activities and forming partnerships and collaborations with other companies. For instance, In December 2021, Novartis received the US Food and Drug Administration approval of Leqivo (inclisiran), for the treatment of adults with clinical atherosclerotic cardiovascular disease and other indications. In June 2020, The Korea Advanced Institute of Science and Technology developed a new nanoparticle drug combination for atherosclerosis. Key Companies Profiled by Fact.MR GlaxoSmithKline Plc Sanofi Hoffmann-La Roche Ltd Bayer AG Novartis AG Merck & Co., Inc. (Merck Sharp & Dohme Corp) Janssen Pharmaceuticals, Inc. (Johnson & Johnson) Mylan N.V. Amgen Inc. Pfizer, Inc. More Valuable Insights on Atherosclerosis Drugs Market In the latest study, Fact.MR offers a detailed study on global atherosclerosis drugs market for the forecast period of 2020 to 2027. This study also highlights key drivers promoting the sales of Atherosclerosis Drugs through detailed segmentation as follows: Drug Class Anti-platelet Medications Cholesterol Lowering Medications Fibric Acid and Omega-3 Fatty Acid Derivatives Beta Blockers Angiotensin-converting Enzyme (ACE) Inhibitors Calcium Channel Blockers Diuretics Others Distribution Channel Retail Pharmacies Hospital Pharmacies Online Pharmacies Region North America Europe Asia Pacific Latin America Middle East & Africa Get Full Access of this Report through our Secure Payment Gateway Key Questions Covered in the Atherosclerosis Drugs Market Report What is the projected value of the atherosclerosis drugs market in 2020? At what rate will the global atherosclerosis drugs market grow until 2027? Which are the factors hampering the growth in the atherosclerosis drugs market? Which region is expected to lead in the global atherosclerosis drugs market during 2020-2027? Which are the factors driving the atherosclerosis drugs market during the forecast period? What is the expected market value of the atherosclerosis drugs market during the forecast period? Explore Fact.MR's Coverage on the Healthcare Domain Diuretic Drugs Market: As per Fact.MR, the global diuretic drugs market is set to grow at 3.5% CAGR during the forecast period (2018-2028), owing to the rising prevalence of hypertension across the world. Diuretics have become a common treatment for patients suffering from medical conditions like high blook pressure, kidney stones, and heart failure. Thus, increasing cases to these medical conditions will boosts ales of diuretic drugs through 2028. Omega-3 Fatty Acids Market : Fact.MR predicts the global omega-3 fatty acids market to surpass a valuation of US$ 2.2 billion by 2028. Rising applications of omega-3 fatty acids in pharmaceutical, food & beverages, dietary supplement, and pet food industries is a key factor propelling demand for omega-3 fatty acids in the market. Bronchial Blocker Devices Market : The global bronchial blocker devices market is projected to expand at 5.6% CAGR through 2026. Rising number of thoracic surgeries performed worldwide and with growing need for efficient medical devices are some of the key factors providing impetus to the global bronchial blocker devices market. About Fact.MR Fact.MR is a market research and consulting agency with deep expertise in emerging market intelligence. Spanning a wide range – from automotive & industry 4.0 to healthcare, technology, chemical and materials, to even the most niche categories. We are committed to deliver insights that help businesses gain deeper understanding of their target markets. Specialties: Competition Tracking, Customized Research, Syndicated Research, Investment Research, Social Media Research, Business Intelligence, Industry Analysis, Thought Leadership. Contact: Mahendra Singh US Sales Office 11140 Rockville Pike Suite 400 Rockville, MD 20852 United States Tel: +1 (628) 251-1583, +353-1-4434-232 (D) E: [email protected] Follow Us: LinkedIn | Twitter | YouTube Logo: SOURCE Fact.MR

Drug Approval

17 Nov 2022

·www.sciencedaily.com

Toxins from harmful algae found in bull sharks of Florida's Indian River Lagoon

The Indian River Lagoon (IRL) is a bull shark nursery habitat crucial to survival and recruitment of Atlantic coast bull sharks. Analysis of 123 samples found the presence of one or more phycotoxin from harmful algal blooms in 82 percent of the bull sharks and their prey items. Findings highlight the potential threat of toxic algae to the IRL's ecosystem and surrounding human populations that may consume the same prey species. The highest concentrations of most toxins were detected in gut content samples, highlighting dietary exposure as an important mechanism of toxin transfer to bull sharks in the system. Stretching 251 kilometers along Florida's East Coast, the Indian River Lagoon has experienced large-scale, frequent blooms of toxic harmful algae in recent decades. Harmful algal blooms (HABs) occur when an overgrowth of aquatic microalgae over-accumulate in a body of water, negatively affecting wildlife and humans and degrading aquatic habitats. HAB species produce phycotoxins, potent chemicals produced by photosynthetic organisms, which can move through multiple levels of aquatic food webs as they accumulate and are transferred from prey to predator. Sentinel, or indicator, species can provide an integrated picture of contaminants in the environment. Researchers from Florida Atlantic University's Harbor Branch Oceanographic Institute, in collaboration with the Florida Institute of Technology and the University of Connecticut, are the first to measure multiple phycotoxin concentrations in bull sharks (Carcharhinus leucas) in the Indian River Lagoon, an estuary of national significance. In a prior study, the FAU Harbor Branch researchers confirmed the value of the Indian River Lagoon as a bull shark nursery habitat crucial to survival and recruitment of Atlantic coast bull sharks. In recent decades, human water pollution has compromised the biological integrity of the lagoon, which may continue to degrade if environmental pollution in the area continues. For the current study, researchers measured concentrations of phycotoxins in samples collected from 50 immature (young) bull sharks captured in the Indian River Lagoon between 2018 and 2020. They used ultra-performance liquid chromatography/tandem mass spectrometry to measure the toxins in shark gut contents, plasma (blood) and liver. Results, published in the journal Science of the Total Environment, suggest multiple phycotoxins in the Indian River Lagoon are widespread or persistent in the environment. Analysis of 123 samples demonstrated the presence of multiple phycotoxins (microcystin, nodularin, teleocidin, cylindrospermopsin, domoic acid, okadaic acid and brevetoxin) in sampled bull sharks. The highest concentrations of most toxins were detected in gut content samples, highlighting dietary exposure as an important mechanism of toxin transfer to bull sharks in the system. "The presence of one or more phycotoxin in 82 percent of the bull sharks sampled in our study and their prey items highlights the potential threat of toxic algae to the Indian River Lagoon ecosystem and surrounding human populations that may consume the same prey species," said Michelle L. Edwards, corresponding author, former field technician and marine science and oceanography graduate student at FAU Harbor Branch. Other than brevetoxin, all of the detected toxins (microcystin, nodularin, teleocidin, cylindrospermopsin, domoic acid, okadaic acid) were present in plasma samples. "Due to their ecology within the Indian River Lagoon, including residence during early life stages and use of distinct regional areas, bull sharks in the system served as an appropriate sentinel species to survey toxins," said Matt Ajemian, Ph.D., senior author, an assistant research professor and director of The Fish Ecology and Conservation Lab at FAU Harbor Branch. "In addition, the integrative nature of using gut contents of an upper-level predator for assessment of toxin presence, allowed us to identify toxins in several lower trophic species, including stingrays, catfishes and mullet." One important vector species for the transfer of phycotoxins to bull sharks in the Indian River Lagoon was the most commonly identifiable prey item in the study: mullet. In fact, 60 percent of gut contents in which microcystin was identified contained mullet. "Mullet are distributed throughout the Indian River Lagoon and migrate to offshore areas to spawn between September and December each year, a similar pattern to seasonal offshore movements by young bull sharks that spend time in offshore areas between October and March each year," said Edwards. Most toxins were detected in samples collected from all three regions of the Indian River Lagoon (North, Central, South) and during both "wet" and "dry" seasons despite the tendency of resident bull sharks to spend most of their time in specific regions with varied seasonal area usage such as offshore area movements. "Many phycotoxins can remain in the environment after a harmful algal bloom period ends," said Ajemian. "Both microcystin and domoic acid, an acid-type neurotoxin, which was the most commonly detected toxin we found in the bull sharks in our study, can adsorb to sediments and could be ingested by benthic organisms or become resuspended in the water column. This makes tracing the timing of exposure to these toxins a tremendous challenge." The higher concentrations in gut contents compared to other tissues of the shark suggest that although Indian River Lagoon-resident bull sharks may be frequently exposed to phycotoxins, they may not accumulate them compared to lower trophic species. "Research on the potential for accumulation in other shark tissues not sampled in our study may be warranted," said Edwards. According to Ajemian, they have just scratched the surface on what HAB exposure means for bull sharks in the Indian River Lagoon. "This was an essential first step in developing critical baselines as we continue to monitor the responses of these animals to HABs in the future," said Ajemian. Study co-authors are Adam M. Schaefer, Abt Associates; Malcolm McFarland, Ph.D., an assistant research professor, FAU Harbor Branch; Spencer Fire, Ph.D., an associate professor, Florida Institute of Technology; and Christopher R. Perkins, Ph.D., environmental laboratory director, University of Connecticut. This work was supported by the Disney Conservation Fund, SeaWorld and Busch Gardens Conservation Fund, the Harbor Branch Oceanographic Institute Foundation, and Florida Center for Coastal and Human Health. Edwards was additionally supported by the Sunrise Rotary Club of Vero Beach.

14 Nov 2022

·www.sciencedaily.com

High-fat diet can provoke pain sensitivity without obesity, diabetes

A new study in mice suggests that a short-term exposure to a high-fat diet may be linked to pain sensations even in the absence of a prior injury or a preexisting condition like obesity or diabetes. The study found that a high-fat diet induced hyperalgesic priming -- a neurological change that represents the transition from acute to chronic pain -- and allodynia, which is pain resulting from stimuli that do not normally provoke pain. A new study in mice from researchers at The University of Texas at Dallas suggests that a short-term exposure to a high-fat diet may be linked to pain sensations even in the absence of a prior injury or a preexisting condition like obesity or diabetes. The study, published Sept. 1 in the journal Scientific Reports, compared the effects of eight weeks of different diets on two cohorts of mice. One group received normal chow, while the other was fed a high-fat diet in a way that did not precipitate the development of obesity or high blood sugar, both of which are conditions that can result in diabetic neuropathy and other types of pain. The researchers found that the high-fat diet induced hyperalgesic priming -- a neurological change that represents the transition from acute to chronic pain -- and allodynia, which is pain resulting from stimuli that do not normally provoke pain. "This study indicates you don't need obesity to trigger pain; you don't need diabetes; you don't need a pathology or injury at all," said Dr. Michael Burton, assistant professor of neuroscience in the School of Behavioral and Brain Sciences and corresponding author of the article. "Eating a high-fat diet for a short period of time is enough -- a diet similar to what almost all of us in the U.S. eat at some point." The study also compared obese, diabetic mice with those that just experienced dietary changes. "It became clear, surprisingly, that you don't need an underlying pathology or obesity. You just needed the diet," Burton said. "This is the first study to demonstrate the influential role of a short exposure to a high-fat diet to allodynia or chronic pain." Western diets are rich in fats -- in particular saturated fats, which have proved to be responsible for an epidemic of obesity, diabetes and associated conditions. Individuals who consume high amounts of saturated fats -- like butter, cheese and red meat -- have high amounts of free fatty acids circulating in their bloodstream that in turn induce systemic inflammation. Recently, scientists have shown that these high-fat diets also increase existing mechanical pain sensitivity in the absence of obesity, and that they can aggravate preexisting conditions or hinder recovery from injury. No studies, however, have clarified how high-fat diets alone can be a sensitizing factor in inducing pain from nonpainful stimuli, such as a light touch on the skin, Burton said. "We've seen in the past that, in models of diabetes or obesity, only a subsection of the people or animals experience allodynia, and if they do, it varies across a spectrum, and it isn't clear why," Burton said. "We hypothesized that there had to be other precipitating factors." Burton and his team looked for saturated fatty acids in the blood of the mice fed the high-fat diet. They found that a type of fatty acid called palmitic acid -- the most common saturated fatty acid in animals -- binds to a particular receptor on nerve cells, a process that results in inflammation and mimics injury to the neurons. "The metabolites from the diet are causing inflammation before we see pathology develop," Burton said. "Diet itself caused markers of neuronal injury. "Now that we see that it's the sensory neurons that are affected, how is it happening? We discovered that if you take away the receptor that the palmitic acid binds to, you don't see that sensitizing effect on those neurons. That suggests there's a way to block it pharmacologically." Burton said the next step will be to focus on the neurons themselves -- how they are activated and how injuries to them can be reversed. It is part of a larger effort to understand better the transition from acute to chronic pain. "The mechanism behind this transition is important because it is the presence of chronic pain -- from whatever source -- that is fueling the opioid epidemic," he said. "If we figure out a way to prevent that transition from acute to chronic, it could do a lot of good." Burton said he hopes his research encourages health care professionals to consider the role diet plays in influencing pain. "The biggest reason we do research like this is because we want to understand our physiology completely," he said. "Now, when a patient goes to a clinician, they treat a symptom, based off of an underlying disease or condition. Maybe we need to pay more attention to how the patient got there: Does the patient have diabetes-induced or obesity-induced inflammation; has a terrible diet sensitized them to pain more than they realized? That would be a paradigm shift." The study's co-lead authors are Calvin D. Uong BS'22, a lab assistant in Burton's Neuroimmunology and Behavior Lab, and Jessica A. Tierney BS'18, MS'19, now an MD/PhD student at the UT Medical Branch at Galveston. Cognition and neuroscience doctoral student and Eugene McDermott Graduate Fellow Melissa E. Lenert MS'19 and Terry Scholar alumna Marisa Williams BS'19, MS'20 also contributed. The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (R21DK130015), the UT System STARS (Science and Technology Acquisition and Retention) program, the American Pain Society and the Rita Allen Foundation.

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