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PubMed1991

Biological effects of short-term feeding to rats of repeatedly used deep-frying fats in relation to fat mutagen content.

The effects of short-term feeding of mutagen containing, heated deep-frying oils on urinary and faecal mutagenicity, plasma clinical biochemical parameters, peroxidative effects and cell proliferative indices in the gastro-intestinal tract were determined in rats. Repeatedly used frying oils [a saturated fatty acid-rich coconut oil (CO) and a polyunsaturated fatty acid (PUFA)-rich (greater than 60% PUFA) vegetable frying oil (PO)] were administered to groups of seven rats at a level of 10% (by weight) in the diet for 4 wk; control groups were fed equal amounts of the unheated oils. Both heated oils showed direct-acting mutagenicity to Salmonella tester strain TA97; heated PO was also mutagenic to strain TA100. Both heated CO and heated PO contained detectable amounts of thiobarbituric acid-reactive substances (TBA-RS). In heated PO, hydroperoxides of linoleic acid were also present. In groups fed heated oils the mutagenicity of urine and faeces to strain TA97 was not found to be increased in comparison with the control groups. Faecal mutagenicity to strain TA100 was also unaffected by consumption of heated oils. Urinary excretion of TA100 mutagens was significantly increased in rats fed heated PO. Plasma alkaline phosphatase activity was clearly raised in rats fed heated PO, in comparison with rats fed unheated oils or heated CO. In addition, other clinical biochemical plasma parameters showed a tendency to be increased in rats fed heated PO, indicating hepatic and renal cellular toxicity. Urinary and faecal excretion of thiobarbituric acid-reactive substances (TBA-RS) were also slightly, but not significantly, increased in rats fed heated PO. Feeding heated CO to rats did not result in increased plasma enzyme activities and excretion of TBA-RS, nor in increased cell proliferation in gastro-intestinal tissues. Cell proliferation of the oesophageal tissues were slightly, but significantly, increased in rats fed heated PO, in comparison with the group fed unheated PO. Tissues of the glandular stomach and colon/rectum did not show significantly enhanced cell proliferation in the group fed heated PO. The results obtained in this study indicated that consumption of heated oils containing TA100 mutagens and oxidation products of linoleic acid produced indications of cellular damage to liver and kidneys, and increased urine mutagenicity, as well as enhanced cell proliferation in the oesophagus.

Administration, Oral↗

PubMed2005

Detection of cytotoxic activity of Psacalium palladium on normal mouse spleen cells and transformed human cells.

A decoction from roots and rhizomes of Psacalium palladium is used in Mexico for the treatment of tumors and for control of diabetes mellitus, among other ailments. Although hypoglycemic activity has been demonstrated in various experimental models and some compounds have been detected in the roots and rhizomes, such as alkaloids, glycosides and tannins, toxicity studies have not yet been performed. Moreover, since various species taxonomically related to P. palladium have pyrrolizidine alkaloids (hepatotoxic, carcinogenic and mutagenic agents) it is possible that these species also contain potentially toxic substances, which represents a risk for users. The aim of this investigation was study the cytotoxicity of P. palladium on mouse hematopoietic cells and transformed human cells, evaluating the cell proliferation by the technique of sulforhodamine B. An aqueous fraction (AS) reduced population of both types of cells by over 50%; meanwhile the other extracts did not alter cell number. Fraction AP was cytotoxic for DU-145 cells at 10 microg/mL, whereas the remaining extracts acted like cytostatic agents.

Animals↗

PubMed1997

Povidone-iodine liposomes--an overview.

In recent years, liposomes have been increasingly explored as novel drug delivery systems, and several liposome-based drug products have been approved in Europe, the USA and Japan. Depending on size, composition and surface characteristics, liposomes interact specifically with biological structures. Liposomal drug products provide a topical activity at the desired locus of action and are deemed more effective and less toxic than conventional drug formulations. The combination of povidone-iodine (PVP-I) and liposomes unites the exceptional microbicidal activity of the antiseptic substance with the excellent tolerability and lack of immunogenicity of liposomes; in addition, liposomes provide a moist molecular film for the wound environment. The multilamellar vesicles act as microreservoirs hence prolonging the release of the active ingredient. Although no commercial product for repeated application on the eye is currently available, PVP-I has been used in ophthalmology not only for pre- and postoperative antisepsis, but also for the treatment of bacterial and viral conjunctivitis and for prophylaxis against ophthalmia neonatorum. For these indications, liposomal formulations with 2.5 and 5.0% PVP-I were developed. These eye drops are isotonic with tear fluid at pH 6. First in vitro tests demonstrated an excellent antimicrobial efficacy, and a placebo-controlled clinical study on volunteers showed a very good local tolerability. A study on rabbits demonstrated positive results of the PVP-I liposome eye drops compared to placebo and the broadspectrum antibiotic Polyspectran in a standardized model of Staphylococcus aureus deep eye infection. The other aim is a well-tolerated liposomal PVP-I hydrogel for improved antiseptic wound treatment with moisturizer. It has been reported that liposomes are enriched at the wound bottom for direct action against infection and support of wound healing. An animal study on the efficacy and tolerability of different formulations of a hydrogel with PVP-I liposomes in deep dermal burn wounds has indicated an outstanding quality of wound healing with smooth granulation tissue, less inflammation, less wound contraction and no hyperkeratotic reactivity, especially with the 3% PVP-I liposome formulation.

Administration, Cutaneous↗

PubMed1996

[Experimental study on homoiothermic extracorporeal liver preservation].

To prove that perfused liver can be preserved at room temperature (22 degrees C), we made the experiment, in which HTK was basic solution, perfluorocarbon acted as oxygen carrier and lipid acted as energy substrate in the homoiothermy condition, pig liver organs were perfused extracorporeally through the V. portal with perfusion solution. In fixed period of time the perfusion solution from the liver was taken and analysed to determine for liver biochemical function and observe the concentration and size of hepatocellular mitochondria. In oxygen carrier perfusion solution the ammonia concentration was low, urea concentration was high, damage to mitochondria was minimum and by addition of lipid emulsion the concentration of glucose can be maintained. The experimental and control data were obviously significant. The result demonstrated that oxygen carrier (perfluorocarbon) as oxygen supplier can provides enough oxygen to liver cell, at the sametime, lipid emulsion intralipid) provides energy so as the perfused liver can be preserved at high temperature, i.e. 22 degrees C at relative long time (40 hours) and still has the function of removing toxic substance such as ammonia and converting it to urea, meanwhile maintain the normal structure of mitochondria. The preservation of perfused liver at homoiothermy is possible.

Animals↗

PubMed2004

Complexation of arsenate with humic substance in water extract of compost.

The interactions of environmental toxicants with organic substances affect the speciation and dynamics, and subsequent toxicity, mobility, and fate of toxicants in the environment. For the purpose of understanding the complexation of As(V) with humic substances, arsenate-containing solutions with As concentrations from 1 to 8 mgl(-1) were prepared to react with the water extract of compost (WEC). All the reaction systems including the control were incubated for 48 h at 25 degrees C. The complexation of As(V) with humic substance was examined by dialysis and ion exchange techniques. From 30% to 51% of added As(V) reacted with organic substance in WEC to form an As-metal-organic complex. This was verified as a hydrophobic organic fraction after separation of As-metal-organic complex fraction from the hydrophilic fraction by XAD-8 resin. The complex substance was also identified as a humic substance by the method of proton binding formation function determination. This suggests that cations, such as Ca and Mg, and especially Fe, Al, and Mn act in cation bridging in the complexation of As(V) with humic substance. The role of metals in the complexation of As(V) with humic substance in terrestrial and especially aquatic environments thus merits close attention.

Arsenates↗

PubMed2005

Aspirin modulates LPS-induced nitric oxide release in rat glial cells.

Nitric oxide and prostaglandins are among the numerous substances released by activated glial cells. The aim of this study was to evaluate the effect of high-level aspirin on iNOS expression in cultured rat glial cells treated with lipopolysaccharide (LPS) as pathological stimulator. Using Western Blotting, we verified that aspirin enhanced LPS-induced iNOS expression and the presence of 15-deoxy-Delta(12,14)-prostaglandin (15d-PGJ2) suppressed this aspirin effect. However, the exposure of LPS-treated glial cells to aspirin resulted in a decrease of NO production. These results suggest that aspirin interferes with the cross-talk of prostaglandins and NO, blocking the endogenous negative control exerted by COX products on iNOS expression. On the other side, aspirin seems to act directly on iNOS reducing its activity, even if it does not completely block NO release by LPS-stimulated glial cells. Then aspirin could maintain homeostatic functions of NO, while it prevents toxic effects, corresponding to high NO concentrations.

Animals↗

PubMed2003

Comparative effects of vetiver oil, nootkatone and disodium octaborate tetrahydrate on Coptotermes formosanus and its symbiotic fauna.

The potential of vetiver oil and nootkatone as wood treatments against Coptotermes formosanus Shiraki was examined by assessing the effects on termite tunneling, feeding activity and survival, and the consequences on the symbiont protozoa responsible for wood digestion. Comparisons were made with non-treated wood (control), wood treated with the borate compound Tim-Bor (a commonly used lumber preservative) and absence of a food source (starved termites), using choice and no-choice tests. All wood slices were prepared at the same time using a 10 g liter(-1) solution of each substance and were tested in four different sessions over one year to investigate longevity of the effects. Termites had to tunnel through sand to exploit the food sources, consisting of two wood slices, placed on opposite sides of the experimental enclosure. No-choice tests showed that in the presence of vetiver oil or nootkatone, tunneling activity was always the lowest; wood consumption, termite survival and flagellate numbers and species distribution were significantly different from the control and similar to the results obtained for starved termites and with Tim-Bor-treated wood. Nootkatone negatively affected termites for 12 months and was longer lasting than vetiver oil. In choice tests, when vetiver oil or nootkatone were present, termites exhibited a significant preference for non-treated wood. Our results confirmed both the toxicity and absence of repellency of Tim-Bor. Vetiver oil and especially nootkatone affected Formosan subterranean termites and their protozoa, acting as arrestants, repellents and feeding deterrents, and represent a promising natural alternative for the control of this invasive pest.

Animals↗

PubMed1993

NTP technical report on the toxicity studies of Pesticide/Fertilizer Mixtures Administered in Drinking Water to F344/N Rats and B6C3F1 Mice.

Toxicity studies were performed with pesticide and fertilizer mixtures representative of groundwater contamination found in California and Iowa. The California mixture was composed of aldicarb, atrazine, 1,2-dibromo-3-chloropropane, 1,2- dichloropropane, ethylene dibromide, simazine, and ammonium nitrate. The Iowa mixture contained alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate. The mixtures were administered in drinking water (with 512 ppm propylene glycol) to F344/N rats and B6C3F1 mice of each sex at concentrations ranging from 0.1x to 100x, where 1x represented the median concentrations of the individual chemicals found in studies of groundwater contamination from normal agricultural activities. This report focuses primarily on 26-week toxicity studies describing histopathology, clinical pathology, neurobehavior/neuropathology, and reproductive system effects. The genetic toxicity of the mixtures was assessed by determining the frequency of micronuclei in peripheral blood of mice and evaluating micronuclei and sister chromatid exchanges in splenocytes from female mice and male rats. Additional studies with these mixtures that are briefly reviewed in this report include teratology studies with Sprague-Dawley rats and continuous breeding studies with CD-1 Swiss mice. In 26-week drinking water studies of the California and the Iowa mixtures, all rats (10 per sex and group) survived to the end of the studies, and there were no significant effects on body weight gains. Water consumption was not affected by the pesticide/fertilizer contaminants, and there were no clinical signs of toxicity or neurobehavioral effects as measured by a functional observational battery, motor activity evaluations, thermal sensitivity evaluations, and startle response. There were no clear adverse effects noted in clinical pathology (including serum cholinesterase activity), organ weight, reproductive system, or histopathologic evaluations, although absolute and relative liver weights were marginally increased with increasing exposure concentration in both male and female rats consuming the Iowa mixture. In 26-week drinking water studies in mice, one male receiving the California mixture at 100x died during the study, and one control female and one female in the 100x group in the Iowa mixture study also died early. It could not be determined if the death of either of the mice in the 100x groups was related to consumption of the pesticide/fertilizer mixtures. Water consumption and body weight gains were not affected in these studies, and no signs of toxicity were noted in clinical observations or in neurobehavioral assessments. No clear adverse effects were noted in clinical pathology, reproductive system, organ weight, or histopathologic evaluations of exposed mice. The pesticide/fertilizer mixtures, when tested over a concentration range similar to that used in the 26-week studies, were found to have no effects in teratology studies or in a continuous breeding assay examining reproductive and developmental toxicity. The California and Iowa pesticide mixtures were tested for induction of micronuclei in peripheral blood erythrocytes of female mice. Results of tests with the California mixture were negative. Significant increases in micronucleated normochromatic erythrocytes were seen at the two-highest concentrations (10x and 100x) of the Iowa mixture, but the increases were within the normal range of micronuclei in historical control animals. Splenocytes of male rats and female mice exposed to these mixtures were examined for micronucleus and sister chromatid exchange frequencies. Sister chromatid exchange frequencies were marginally increased in rats and mice receiving the California mixture, but neither species exhibited increased frequencies of micronucleated splenocytes. None of these changes were considered to have biological importance. In summary, studies of potential toxicity associated with the consumption of mixtures of pesticides and a fertilizer representative of groundwater contamination in agriculturative of groundwater contamination in agricultural areas of Iowa and California failed to demonstrate any significant adverse effects in rats or mice receiving the mixtures in drinking water at concentrations as high as 100 times the median concentrations of the individual chemicals determined by groundwater surveys. NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.

Journal Article↗

PubMed2006

Hazardous waste: recognition of the problem and response.

Two accidents, Seveso 1976 and Bhopal 1984, paved the way toward the international control of hazardous substances and waste, and public dissemination of information on their releases and transfers. The final facility cleanup in Seveso took place in 1982. The remaining dioxin-containing residues were packed in 41 drums. However, the drums disappeared and were found several months later in France. This was the starting point for the development of international control on transboundary movements of waste within the OECD. Between 1983 and 1992 OECD developed five binding Council Acts on the classification and control of transboundary movements of waste. This work also provided the foundation for the adoption of a series of directives and the Shipment Regulation 259/93 within the European Community, aimed at monitoring and controlling transboundary movements of hazardous waste, and of a global instrument in 1989 under UNEP: Basel Convention on the Control of Transboundary Movements of Hazardous Waste and Their Disposal. The Bhopal 1984 and another similar accident shortly thereafter led to the development of a mandatory Toxics Release Inventory (TRI) in the United States in 1986, to inform the public of releases and transfers of potentially hazardous pollutants and waste. OECD work has supported the rapidly increasing implementation of Pollutant Release and Transfer Registers (PRTRs) since 1994. The Basel 1989, Rotterdam 1998, and Stockholm 2001 Conventions all require strict control of the production and management of hazardous chemicals and waste. Yet, production of hazardous chemicals and generation of hazardous waste are still in rise.

Hazardous Waste↗

PubMed2003

Exposure to xenobiotic compounds: looking for new biomarkers.

A variety of antropogenic compounds that have an estrogenic effect, and are known to be present in the environment, shows a significant potential for interference with the health and reproduction of both wildlife and humans. In this review, the effect of estrogenic and antiestrogenic chemicals with widely divergent potencies-nonylphenol (NP), which acts by binding with the estradiol response element, and beta-naphthoflavone (beta-NF), a dioxin-like compound that exerts its toxic action through the aryl hydrocarbon receptor-was compared with that induced by 17beta-estradiol (E(2)) in a marine teleost, the Gobius niger, under controlled laboratory experiments. The capacity of these compounds to affect the levels of estrogen-regulated proteins such as cathepsin D (CAT D)-in humans, a protein associated with the development of breast cancer, and, in oviparous vertebrates, with reproductive success-was assessed. The results of this study showed that both the estradiol and the higher dose of NP induce CAT D gene expression and its associated activity. On the contrary, beta-NF treatments inhibited CAT D gene expression and, at lengthier exposure (96 h), its enzymatic activity. Based on these results, we suggest CAT D as a novel bioindicator of the presence of endocrine-disrupting substances in the environment. The other biomarker assessed in this study is the Heath Shock Protein 70 (HSP70); this protein protects cells against harmful conditions by binding and refolding damaged proteins. Interestingly, HSP70 was found to be affected by all the toxicant compounds employed in the study. The HSP70 gene expression was significantly increased by both NP concentrations and the exposure time of beta-NF, with the E(2) being the most potent inducer. These data indicate that HSP70 may provide a useful early warning biomarker for studies on the presence of exogenous pollutants in the environment.

Animals↗

PubMedDate not supplied

Effects of etherlipid analogs on cell membrane functions.

Hexadecylphosphocholine and other etherlipid-derived substances show a pronounced antiproliferative activity on neoplastic cells and a broad spectrum of other biological effects on many cell types in vitro and in vivo. Though the precise molecular mechanism by which these etherlipid analogs act still remains unresolved, it seems clear that it most probably involves some essential function of the cell membrane. We investigated the effect of different etherlipids with and without cytotoxic activity in etherlipid-susceptible and -resistant tumor cell lines on three important membrane functions. We observed various inhibitory activities on endocytosis and the uptake of small precursor molecules as sugars, amino acids, and alcohols by toxic and nontoxic substances in resistant as well as susceptible cells. There was no correlation between the antiproliferative characteristics of the compounds and the effects on these membrane transport functions. Furthermore, the substances reduced the number of membrane tumor necrosis factor-alpha receptors regardless of their antiproliferative properties. The results of these investigations suggest that etherlipid analogs may interfere with many membrane functions in an unspecific manner. Therefore, many of the previously reported biological effects of etherlipids have to be viewed under a different light. Future investigation on these compounds should always contain appropriate control substances and cell models to really prove the specificity of the observed effects.

Animals↗

PubMedDate not supplied

Ascites fluid in severe acute pancreatitis: from pathophysiology to therapy.

Several pathophysiological mechanisms are involved in the development of the inflammatory necrotizing process that takes place in the retroperitoneal area during the early phase of acute pancreatitis. They include premature intraglandular activation of pancreatic proenzymes (zymogens) and in particular trypsin, early microcirculatory impairment with subsequent ischaemia/reperfusion and overstimulation of immune effector cells. Although intra-acinar or interstitial activation of trypsinogen is most probably the trigger of acute pancreatitis, in recent years much emphasis has been put on the role of leukocytes. Based on numerous experimental and human data several pro-inflammatory mediators including cytokines, arachidonic acid derivatives, activated oxygen species and proteases are released locally by overactivated neutrophils and monocytes/macrophages among other cells. They are now believed to play a central role in the development of pancreatic necrosis and, once they gain access to the systemic circulation, in the emergence of early multisystem organ failure. However the sequential and relative contribution of each of these 3 pathophysiological mechanisms remain controversial and the precise identification of the mediators incriminated in local and remote tissue injury is still awaited. Severe acute pancreatitis still carries a mortality of 20% to 30%. With advances in intensive care management 80% of the deaths occur somewhat late in the attack due to infected pancreatic necrosis. Nevertheless early remote organ failures still remain a lifethreatening condition for most of these patients. A peritoneal exudate rich in activated lipolytic and proteolytic enzymes, vasoactive substances and several other pro-inflammatory mediators collect in over 60% of the patients with severe acute pancreatitis. On the basis of favourable animal experiments early percutaneous or surgical peritoneal lavage with or without the addition of antiproteases has been carried out in human acute pancreatitis. The rationale behind this procedure was the washout of potential toxic mediators from the peritoneal cavity before they gain access to the systemic circulation. Contrary to animal and uncontrolled human data no prospective randomized study could ever demonstrated a significant effect of peritoneal lavage neither in the prevention and control of remote organ failures or in early mortality and ultimate survival after severe acute pancreatitis in humans. Differences between experimentally-induced pancreatitis, difference in the timing of the initiation of lavage and a type II error in controlled human studies may account for the discrepancy in the outcome between these studies. Anyway, this disparity should raise the question as whether the peritoneal cavity acts simply as a reservoir or as a route of transfer of toxic mediators to the systemic circulation. Although data are scarce, conflicting and limited to animal experiments and to a few molecules, peripancreatic veins and lymphatics seem to be the major routes of transfer whereas transperitoneal absorption is trivial. Nevertheless early peritoneal aspiration of ascitic fluid in acute pancreatitis and measurement of trypsinogen activation peptides may be used as a means of severity assessment and identification of pancreatic necrosis. This implies that even if not taking part actively in the emergence of remote organ failures ascitic fluid may reflect the peripancreatic necrotizing process. So careful comparative analysis of peritoneal exudate, plasma and lymph with regards to putative mediators of local and remote injury may provide essential pathophysiological clues. At the time of trials of antimediator therapy early in the attack this kind of insight is essential.

Acute Disease↗

PubMed1994

Okadaic acid indicates a major function for protein phosphatases in stimulus-response coupling of RINm5F rat insulinoma cells.

Stimulus-induced insulin secretion involves the activation of several protein kinases within the beta cell. Most prominent are protein kinase A, protein kinase C and calcium/calmodulin-dependent protein kinases. Protein kinase action is functionally antagonized by protein phosphatases. The four ubiquious serine/threonine protein phosphatases are termed PP-1, PP-2A, -2B and -2C. PP-1 and PP-2A are in vivo parts of major protein complexes. These complexes presumably regulate the phosphatase activity and direct the enzyme to its site of action. Therefore, PP-1 and -2A could play an important role in controlling intracellular signal transmission. Two different toxins, okadaic acid and calyculin A, both from marine invertebrates, were recently discovered and identified as potent and highly specific inhibitors of PP-1 and PP-2A. Both compounds emerged as very useful tools for studying intracellular phosphorylation events. We took advantage of these substances to investigate the significance of protein phosphatase action in stimulus-induced insulin secretion. To avoid major complexity, we confined our study to the cAMP and the phosphoinositide signal pathway. Okadaic acid alone evoked virtually no secretory response. cAMP-dependent secretion was markedly enhanced by 1 microM okadaic acid. The stimulatory effect of okadaic acid was strongly dependent on the concentration of cAMP analoga. In contrast, insulin release caused by the cholinergic agonist carbachol was not influenced by okadaic acid. Calyculin A (10 nM) slightly increased cAMP-induced secretion, but its high toxicity prohibited accurate interpretation of the data. Our findings support the idea that serine/threonine phosphatases act as important regulators in stimulus response coupling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Development of the blood-brain barrier.

The endothelial cells forming the blood-brain barrier (BBB) are highly specialized to allow precise control over the substances that leave or enter the brain. An elaborate network of complex tight junctions (TJ) between the endothelial cells forms the structural basis of the BBB and restricts the paracellular diffusion of hydrophilic molecules. Additionally, the lack of fenestrae and the extremely low pinocytotic activity of endothelial cells of the BBB inhibit the transcellular passage of molecules across the barrier. On the other hand, in order to meet the high metabolic needs of the tissue of the central nervous system (CNS), specific transport systems selectively expressed in the membranes of brain endothelial cells in capillaries mediate the directed transport of nutrients into the CNS or of toxic metabolites out of the CNS. Whereas the characteristics of the mature BBB endothelium are well described, the cellular and molecular mechanisms that control the development, differentiation and maintenance of the highly specialized endothelial cells of the BBB remain unknown to date, despite the recent explosion in our knowledge of the growth factors and their receptors specifically acting on vascular endothelium during development. This review summarizes our current knowledge of the cellular and molecular mechanisms involved in the development and maintenance of the BBB.

Animals↗

PubMed2005

Amburoside A, a glucoside from Amburanacearensis, protects mesencephalic cells against 6-hydroxydopamine-induced neurotoxicity.

This study evaluates the potential neuroprotective properties of amburoside A, a glucoside isolated from Amburana cearensis, on rat mesencephalic cell cultures exposure to the neurotoxin 6-hydroxydopamine (6-OHDA). The parameters determined were cell viability by the 3[4,5-dimethylthiazole-2-il]-2,5-diphenyltetrazolium bromide (MTT) method, nitric oxide (NO) and free radical formation by the measurement of nitrite concentration and thiobarbituric acid reacting substance (TBARS) formation as an indication of cellular lipid peroxidation. The results showed that AMB was less effective as a curative agent in the MTT assay, since its addition after 6-OHDA did not reverse the neurotoxin's effect, except at the highest concentration (AMB, 100 microg/ml). Similarly, the higher nitrite levels observed after exposure of the cells to 6-OHDA were only partially reversed by AMB, at this highest concentration. However, when AMB (0.5, 1, 10 and 100 microg/ml) was added before the toxin, it appeared to protect neuronal cells against 6-OHDA toxicity in a concentration-dependent manner, as shown by MTT assay. AMB also prevented free radical formation indicated by the increased nitrite concentration induced by 6-OHDA. Cells exposed to 6-OHDA showed a 3.4 times increase in TBARS concentration as compared to controls, and this effect was inhibited from 24% up to 64% by AMB (0.1-100 microg/ml), indicative of a neuroprotective effect. In conclusion, we show that AMB, acting as an antioxidant compound, presents a significant neuroprotective effect, suggesting that this compound could provide benefits as a therapeutic agent in neurodegenerative disease such as Parkinson's.

Animals↗

PubMed1997

Peptide growth factors but not ganglioside protect against excitotoxicity in rat retinal neurons in vitro.

Glutamate is the major excitatory neurotransmitter in the retina, but excessive stimulation of its receptors leads to widespread neuronal stress and death. Both growth factors and gangliosides display important influences on responses to neuronal injury and degeneration. In this study, we have investigated the potential protective effects of two well characterized growth factors, epidermal and basic fibroblast growth factor (EGF and bFGF respectively), and the monosialoganglioside GM1, on cultured rat retinal neurons submitted to toxic levels of excitatory amino acids. Application of 1 mM glutamic acid reduced global neuronal viability by 80% when compared to control untreated cultures, whereas treatment with the glutamic acid agonist kainic acid (1 mM) led to specific, large decreases (75% reduction) in amacrine cell numbers. 24 h pretreatment with either EGF or bFGF (500 pM each) prevented the majority of excitatory amino acid-induced neuronal death, whereas similar treatment with 10(-5) M GM1 did not block neuronal degeneration. These findings demonstrate that EGF and bFGF act as neuroprotective agents against retinal excitotoxicity in vitro, whereas ganglioside GM1 is not effective in this particular paradigm.

Animals↗

PubMed2003

Hepatoprotective activity of polyhydroxylated 2-styrylchromones against tert-butylhydroperoxide induced toxicity in freshly isolated rat hepatocytes.

2-Styrylchromones are a novel class of chromones, vinylogues of flavones (2-phenylchromones), which have recently been found in nature. The best described property of almost every group of flavones and other flavonoids, especially the hydroxylated derivatives, is their capacity to act as antioxidants. Indeed there is a widely accepted view that the positive health effects of flavones are due to their antioxidant activity. As oxidative stress is a main cause of liver toxicity induced by several hepatotoxicants, agents with the ability to protect the liver against reactive pro-oxidant species may be therapeutically useful. The present study evaluated the possible protective activity of six new synthetic polyhydroxylated 2-styrylchromone derivatives against the pro-oxidant hepatotoxicity exerted by tert-butylhydroperoxide ( t-BHP) in freshly isolated rat hepatocytes. The cells were preincubated with the 2-styrylchromones in the final concentrations of 3.125, 12.5, 25, 50, 100, and 200 microM for 5 min before treatment with 1.0 mM t-BHP for 30 min (throughout this incubation period the cells were exposed to both compounds). The well-known antioxidant 3-hydroxyflavone (quercetin) was used as positive control. At the end of the 30-min incubation period, aliquots of cells suspensions were taken for measurement of lactate dehydrogenase leakage, thiobarbituric acid reactive substances, reduced glutathione, and oxidized glutathione contents. The tested compounds exhibited in vitro protective activity against t-BHP induced hepatotoxicity (1.0 mM, 30 min). Three of the tested compounds, at the concentrations of 3.125, 12.5, 25, and 50 microM, prevented the t-BHP induced glutathione depletion, lipid peroxidation, and cell death in freshly isolated rat hepatocytes to a comparable potency with that of quercetin.

Animals↗

PubMed1999

Antidepressants and suicidal risk.

Only 5% of suicidal patients on the average use their prescribed antidepressant to commit suicide. Underprescription of antidepressants and failure of antidepressant therapy appear to be of greater practical importance than the toxicity of individual compounds. Prescribing less toxic agents, therefore, will not be of great advantage, especially if they are less efficacious. Several antidepressants including the selective serotonin reuptake inhibitors (SSRIs) may increase suicidal behavior by energizing depressed patients to act along preexisting suicidal thoughts or by inducing akathisia with associated self-destructive impulses. For acutely suicidal patients, the use of more sedating antidepressants is recommended. Clinical trials could not confirm a superiority of SSRIs over tricyclics in reducing the number of suicide attempts. There is evidence from large international data sources and a large multicenter controlled trial that lithium prophylaxis decreases the suicide risk and overall mortality in affective disorders. A suicide-preventing effect has not been demonstrated conclusively for antidepressants or non-lithium mood stabilizers.

Antidepressive Agents↗