Lipid peroxidation in fatty liver induced by caffeine in rats.

An increase in lipid peroxidation has been found in liver after poisoning with hepatotoxic substances and following dietary changes, i.e. choline-devoid diet and orotic acid-rich diet. In this study we analysed in the rat a model of fatty liver induced by administration of caffeine. The results seem to indicate an increased peroxidability in the liver of caffeine-treated animals, due to an increase in triglyceride content. A decrease of vitamin E which also occurs might contribute to the lipid peroxidation.     

MR Denoising Increases Radiomic Biomarker Precision and Reproducibility in Oncologic Imaging

Journal of Digital Imaging - Several noise sources, such as the Johnson–Nyquist noise, affect MR images disturbing the visualization of structures and affecting the subsequent extraction of...     

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid

Objectives

The intravenous injection of bisphosphonates, currently used as treatment for osteoporosis, bone Paget’s disease, multiple myeloma, or bone metastases, can cause jaw bone necrosis especially in consequence of trauma. The present research aimed to clarify the mechanisms underlying bone necrosis, exploring involvement of the oral mucosa “in vivo.”

Patients and methods

Specimens of oral mucosa were removed from bisphosphonate-treated patients with or without jaw bone necrosis. In mucosa specimens, expression was evaluated of: cytokines involved in the inflammatory process, factors involved in osteoclast activity, i.e., receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin, a factor involved in cell proliferation, namely hydroxymethylglutaryl coenzyme A reductase, and a factor involved in angiogenesis, namely vascular endothelial growth factor (VEGF).

Results

Interleukin (IL)-6 and the RANK/osteoprotegerin ratio were significantly elevated in mucosa from patients with versus without jaw necrosis, whereas hydroxymethylglutaryl coenzyme A reductase and VEGF were significantly decreased.

Conclusions

Our results suggest that mucosa, stimulated by bisphosphonate released from the bone, can contribute to the development of jaw necrosis, reducing VEGF, and producing IL-6 in consequence of hydroxymethylglutaryl coenzyme A reductase reduction. In turn, IL-6 stimulates osteoclast activity, as shown by the increased RANKL/osteoprotegerin ratio.

Clinical relevance

The results of this study suggest the importance of evaluating during bisphosphonate treatment the production of IL-6, RANKL, osteoprotegerin, and VEGF, in order to monitor the jaw osteonecrosis onset. To avoid repeated mucosa excisions, the determination of these factors could be carried out in crevicular fluid.     

Tissue protein turnover during liver carcinogenesis

Overall rates of tissue protein degradation in vivo during chemicalhepatocarcinogenesis were estimated by a double-isotope methodas well as from the accumulation of peptide intermediates inprotein degradation induced by bestatin. Several parametersestimating rates of cell proliferation and cell loss have beenmeasured in parallel. The two procedures adopted consistentlyindicated that protein turnover was significantly slowed downthrough the whole observation period (12 months after the initiatingadministration of DENA) in both ‘preneoplastic’nodules and hepatomas as compared with control livers or perinodulartissue. Such a difference may confer a selective growth advantageto ‘preneoplastic’ and tumoral cells. Since proteindegradation rates did not appreciably differ between nodulesand hepatomas, either such advantage originated from some earlystep in the carcinogenetic process or it merely reflected theproliferative events in the two cell populations. Yet neitherliver nodules nor hepatomas were characterized by very highrates of cell proliferation, however much increased with respectto control liver.     

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.     

An overview of the effect of linoleic and conjugated-linoleic acids on the growth of several human tumor cell lines

Both n-6 and n-3 polyunsaturated fatty acids are dietary fats important for cell function, being involved in several physiologic and pathologic processes, such as tumorigenesis. Linoleic acid and conjugated linoleic acid, its geometrical and positional stereoisomer, were tested on several human tumor cell lines originating from different tissues and with different degrees of malignancy. This was to provide the widest possible view of the impact of dietary lipids on tumor development. While linoleic acid exerted different effects, ranging from inhibitory to neutral, even promoting growth, conjugated linoleic acid inhibited growth in all lines tested and was particularly effective against the more malignant cells, with the exception of mammary tumor cells, in which behavior was the opposite, the more malignant cell line being less affected. The inhibitory effect of conjugated linoleic acid on growth may be accompanied by different contributions from apoptosis and necrosis. The effects of conjugated linoleic acid on growth or death involved positive or negative variations in PPARs. The important observation is that a big increase of PPARalpha protein occurred in cells undergoing strong induction of apoptosis, whereas PPARbeta/delta protein decreased. Although PPARalpha and PPARbeta/delta seem to be correlated to execution of the apoptotic program, the modulation of PPARgamma appears to depend on the type of tumor cell, increasing as protein content, when inhibition of cell proliferation occurred. In conclusion, CLA may be regarded as a component of the diet that exerts antineoplastic activity and its effect may be antiproliferative or pro-apoptotic.     

Anti-inflammatory and smooth muscle relaxant activities of the hydroalcoholic extract and chemical constituents from Amburana cearensis A C Smith

Amburana cearensis A. C. Smith, Fagaceae, is a medicinal plant commonly known as 'cumaru' and used in Northeast Brazil for the treatment of respiratory tract diseases. In the present work, we investigated the anti-inflammatory and smooth muscle relaxant activities of the hydroalcoholic extract (HAE), coumarin (Coum) and fl avonoid fraction (FF) isolated from the trunk barks of Amburana cearensis A. C. Smith. It was shown that HAE (200 and 400 mg/kg), Coum (20 and 40 mg/kg) and FF (40 mg/kg), administered orally, significantly inhibited both leukocyte and neutrophil migrations, in the carrageenan or N-formyl-methyl-leucyl-phenylalanine (fMLP)-induced migration in rat peritoneal cavity. The increase in cutaneous vascular permeability induced by serotonin in rats was significantly blocked by HAE (150 mg/kg, i.p.), Coum (5 mg/kg, i.p.) and FF (20 mg/kg, i.p.). However, only HAE blocked the histamine effect on Evans blue extravasation. In the guinea-pig trachea precontracted with carbachol (0.3 microM), histamine (0.1 microM) or KCl (0.1 M), the HAE, Coum and FF evoked a concentration-dependent relaxation in the presence of the three agonists. HAE (100-800 microg/ml) and Coum (4-32 microg/ml) also caused significant relaxation of the rat vas deferens previously contracted with adrenaline, acetylcholine or barium chloride. In addition, HAE, Coum and FF inhibited the histamine and serotonin-induced increase of cutaneous vascular permeability in rats.