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M C Terencio

Publications and source records attributed to M C Terencio.

33 records · Page 2Linked to original sources
PubMed1997

Diclofenac sodium and cyclosporin A inhibit human lens epithelial cell proliferation in culture.

PURPOSE: To investigate the effect of diclofenac sodium salt and cyclosporin A (CsA) on human lens epithelial cell (HLEC) growth in culture. METHODS: Cultures of HLEC were obtained from anterior capsules from extracapsular cataract surgery. Third-passage cells were seeded in 96-well plates in 0.1 ml culture medium. Cytotoxicity was estimated by the tetrazolium test in confluent monolayers after 24 h exposure to a wide range of concentrations of diclofenac and CsA. The effect of subcytotoxic concentrations of diclofenac and CsA on HLEC proliferation in subconfluent cultures was evaluated after 24 and 72 h of exposure. To investigate the relationship between PGE2 synthesis and the inhibitory effect of these drugs, after 24 h of exposure to diclofenac and CsA the production of PGE2 was measured by radioimmunoassay. We also tested the effect of exogenous PGE2 addition to diclofenac 72-h-treated cultures. RESULTS: Diclofenac and CsA (at concentrations > or = 65 microM and > or = 2.5 microM, respectively) inhibited the proliferation of subconfluent cultures of HLEC in a dose-dependent fashion. Diclofenac inhibits PGE2 synthesis, while CsA at high doses stimulates PGE2 synthesis of cultured HLEC. Exogenous PGE2 addition reversed in part the inhibitory effect of diclofenac. CONCLUSIONS: Diclofenac and CsA at appropriate doses are effective in inhibiting cultured HLEC proliferation. This could be of interest to prevent posterior capsule opacification. Further in vivo experimental studies seem worthwhile.

Aged↗
PubMed1996

Inhibition of inflammatory responses by a series of novel dolabrane derivatives.

Four dolabrane derivatives isolated from Endospermum diadenum have been studied for their inhibitory effects on murine models of inflammation and human neutrophil functions in vitro. After topical application, akendo 1, akendo 2 and akendo 3 potently inhibited the mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate (TPA) with a striking effect on myeloperoxidase levels. After oral administration, akendo 2 and akendo 3 inhibited mouse paw oedema induced by carrageenan, with a significant reduction in myeloperoxidase levels. In contrast to indomethacin, they did not modify the prostaglandin E2 content of the inflammed paw. None of the compounds affected superoxide generation by human neutrophils. On the contrary, they inhibited degranulation induced by different stimuli. The most effective compounds were akendo 2 and akendo 3, which also inhibited myeloperoxidase activity. All compounds were weak inhibitors of leukotriene B4 synthesis and release by human neutrophils, whereas only akendo 3 decreased 5-lipoxygenase activity. Cyclo-oxygenase-1 from human platelets was inhibited mainly by akendo 2 and akendo 3, although with a low potency. The latter compound also reduced weakly the synthesis of prostaglandin E2 by cyclo-oxygenase-2. The anti-inflammatory activity of these dolabrane derivatives was not related to arachidonic acid mobilization or metabolism.

Animals↗
PubMed1996

Inhibition of phospholipase A2 activities and some inflammatory responses by the marine product ircinin.

The marine product ircinin has been tested for its effects on secretory and cytosolic phospholipase A2 (PLA2) activities in vitro as well as for inhibition of cellular functions in human neutrophils and inflammatory responses in mice. Ircinin inhibited Naja naja venom, human synovial recombinant, bee venom and zymosan-injected rat air pouch PLA2 with IC50 values in the microM range, similar to those of the known inhibitor scalaradial. On the other hand, ircinin was less active on cytosolic PLA2 from human monocytes and decreased potently the release of LTB4 in human neutrophils. This marine product affected weakly human neutrophil functions like superoxide generation and degranulation. In the zymosan-injected rat air pouch ircinin inhibited in vivo the activity of PLA2 present in exudates and reduced dose-dependently myeloperoxidase levels, whereas cell migration was inhibited only at the highest dose tested. This compound exerted a potent anti-oedematous effect after topical application in the mouse ear oedema test. Ircinin is a new inhibitor of PLA2 activity and our results suggest a potential role for this marine product as an inhibitor of inflammatory processes.

Analysis of Variance↗
PubMed1996

Involvement of secretory phospholipase A2 activity in the zymosan rat air pouch model of inflammation.

1. In the zymosan rat air pouch model of inflammation we have assessed the time dependence of phospholipase A2 (PLA2) accumulation in the inflammatory exudates as well as cell migration, myeloperoxidase activity, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels. 2. A significant increase in PLA2 activity was detected in 1,200 g supernatants of exudates 8 h after injection of zymosan into rat air pouch. This event coincided with peaks in cell accumulation (mainly neutrophils) and myeloperoxidase activity in exudates and was preceded by a rise in eicosanoid levels. 3. This enzyme (without further purification) behaved as a secretory type II PLA2 with an optimum pH at 7-8 units, lack of selectivity for arachidonate release and dependence on mM calcium concentrations for maximal activity. 4. The PLA2 inhibitors manoalide and scalaradial inhibited this enzyme activity in vitro in a concentration-dependent manner. Scalaradial also inhibited zymosan stimulated myeloperoxidase release in vitro. 5. Injection of the marine PLA2 inhibitor scalaradial together with zymosan into the pouch at doses of 0.5, 1 and 5 mumol per pouch resulted in a dose-dependent inhibition of PLA2 activity in exudates collected 8 h later. Myeloperoxidase levels and cell migration were also decreased, while eicosanoid levels were not modified. 6. Colchicine administration to rats prevented infiltration and decreased PLA2 levels in the 8 h zymosan-injected air pouch. 7. These results indicate that during inflammatory response to zymosan in the rat air pouch a secretory PLA2 activity is released into the exudates. The source of this activity is mainly the neutrophil which migrates into the pouch. 8. Scalaradial exerts anti-inflammatory effects in the zymosan air pouch.

Analysis of Variance↗
PubMed1995

Immunochemical detection of protein adducts in cultured human hepatocytes exposed to diclofenac.

The non-steroidal anti-inflammatory drug diclofenac is reported to cause, in rare cases, fulminant hepatic necrosis associated with chronic use of the drug. In order to investigate the possibility that covalent protein adducts of reactive metabolites of diclofenac might be responsible for the hepatotoxicity produced by this drug, we developed an antibody against a diclofenac-keyhole limpet hemocyanin adduct. The anti-diclofenac antibody did recognize diclofenac-protein adducts on Western blots of homogenates of cultured human hepatocytes exposed to diclofenac. The major detected adduct was a 60 kDa protein, which was present in both human and rat hepatocytes. These results suggest that binding of diclofenac to human hepatocytes is, like in rats, selective and that a 60 kDa protein appears to be the major target for alkylation. Immunoblots of homogenates of liver sinusoidal lining cells (LSLC) from rats treated with diclofenac also exhibited adducts with a 60 kDa protein. This fact suggest a role for LSLC in processing of chemically altered proteins in the liver.

Alkylation↗
PubMed1995

Effects of marine 2-polyprenyl-1,4-hydroquinones on phospholipase A2 activity and some inflammatory responses.

Three 2-polyprenyl-1,4-hydroquinone derivatives (2-heptaprenyl-1,4-hydroquinone: IS1, 2-octaprenyl-1,4-hydroquinone: IS2 and 2-[24-hydroxy]-octaprenyl-1,4-hydroquinone: IS3) isolated from the Mediterranean sponge Ircinia spinosula, were evaluated for effects on phospholipase A2 activity of different origin (Naja naja venom, human recombinant synovial fluid and bee venom), as well as on human neutrophil function and mouse ear oedema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). IS1 interacted minimally with these responses. In contrast, IS2 and IS3 inhibited human recombinant synovial phospholipase A2 in a concentration-dependent manner, with minor effects on the rest of the enzymes. Both compounds slightly affected superoxide generation and degranulation in human neutrophils, whereas they decreased thromboxane B2 and leukotriene B4 synthesis and release in a mixed suspension of human platelets and neutrophils stimulated by ionophore A23187, with IC50 values in the microM range. IS3 was the most effective inhibitor of the synthesis of thromboxane B2 by human platelet microsomes and of leukotriene B4 by high speed supernatants from human neutrophils. IS2 and IS3 showed topical anti-inflammatory activity against the TPA-induced ear inflammation in mice, with similar effects on oedema and a higher inhibition of IS3 on leukocyte migration, estimated as myeloperoxidase activity in supernatants of ear homogenates. Some structure-activity relationships were established since differences in the prenylated chain attached to the hydroquinone moiety result in important modifications of these inflammatory responses.

Animals↗
PubMed1995

Inhibition of inflammatory responses by epitaondiol and other marine natural products.

The marine metabolites pacifenol, stypotriol triacetate and epitaondiol were tested for their effects on a number of inflammatory responses. Epitaondiol exhibited a potent topical anti-inflammatory activity related to inhibition of leukocyte accumulation. The other compounds showed a lower potency, similar to that of indomethacin. None of the compounds affected superoxide generation by human neutrophils but pacifenol effectively inhibited the degranulation response. This compound and epitaondiol decreased the release of eicosanoids with a higher potency on the cyclo-oxygenase pathway. Only epitaondiol inhibited human recombinant synovial phospholipase A2 activity in a concentration-dependent manner.

Animals↗
PubMed1994

Effects of flavonoids on Naja naja and human recombinant synovial phospholipases A2 and inflammatory responses in mice.

Six flavonoid derivatives were tested for their influence on Naja naja and human recombinant synovial phospholipase A2. They showed a selectivity for the last enzyme with IC50 = 14.3, 17.6, 12.2 and 28.2 microM for quercetagetin, kaempferol-3-O-galactoside, scutellarein and scutellarein-7-O-glucuronide, respectively, while reduced effects were observed for hispidulin and hibifolin. After topical application all the flavonoids inhibited 12-O-tetradecanoylphorbol-13-acetate-induced ear oedema in mice with a potency comparable to that of indomethacin and they were also able to inhibit carrageenan-induced mouse paw oedema at a dose of 150 mg/kg p.o. The blockade of the free hydroxyl at C-7 or C-6 reduced the anti-inflammatory activity and also the inhibitory effect on human recombinant synovial phospholipase A2. These results are in accordance with the notion that group II phospholipases A2 may play a role in experimental inflammation, although several mechanisms seems to be involved in the anti-inflammatory effect of this group of flavonoids.

Animals↗
PubMed1994

Influence of a series of natural flavonoids on free radical generating systems and oxidative stress.

1. A series of flavonoids isolated from Indian medicinal plants: kaempferol-3-O-galactoside, hispidulin, nepetin, scutellarein, scutellarein-7-O-glucuronide, hibifolin and morelloflavone were studied for their activity as inhibitors of microsomal lipid peroxidation and scavengers of oxygen free radicals in vitro as well as in a model of xenobiotic toxicity in mouse. 2. All compounds inhibited lipid peroxidation in vitro. The most potent compounds were nepetin (non-enzymic lipid peroxidation) and morelloflavone (enzymic lipid peroxidation) with IC50's in the micromolar range. Some of the compounds behaved as scavengers of hydroxyl radical in the deoxyribose degradation assay, with a calculated rate constant for kaempferol-3-O-galactoside of 1.55 x 10(10) M-1 s-1. 3. Scutellarein and nepetin were found to be inhibitors of xanthine oxidase activity, whereas morelloflavone acted as a scavenger of superoxide generated by hypoxanthine/xanthine oxidase. 4. Treatment of mice with scutellarein, hispidulin, nepetin and kaempferol-3-O-galactoside after bromobenzene intoxication decreased serum glumate-pyruvate transaminase activity, although only the last flavonoid was able to significantly reduce hepatic lipid peroxidation products and to increase the reduced glutathione level. In contrast, morelloflavone increased bromobenzene toxicity.

Animals↗
PubMed1991

Antihypertensive action of a procyanidin glycoside from Rhamnus lycioides.

The antihypertensive action of a procyanidin glycoside isolated from Rhamnus lycioides aerial parts was studied in spontaneously and renal hypertensive rats. This compound, like 20 micrograms/kg i.v. of captopril, produced a very clear in vivo inhibition of angiotensin I converting enzyme when given at a dose of 3 mg/kg i.v.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

A hypotensive procyanidin-glycoside from Rhamnus lycioides ssp. lycioides.

A lyophilized hot water extract of the aerial parts of Rhamnus lycioides L. (Rhamnaceae) produced a lowering of systemic arterial blood pressure in normotensive anaesthetized Wistar rats. An activity-guided fractionation of the methanolic extract led to the isolation of a tetrameric procyanidin-glycoside which produced a clear dose-dependent hypotensive response (1.5-6 mg/kg i.v.). This principle was characterized using acid hydrolysis, thiolytic degradation and spectroscopic methods. It consisted of four flavanol units with a 2,3-cis configuration and with a O-beta-d-glucosylpyranoside function on the epicatechin terminal unit. The interflavan linkage was (4-8).

Animals↗
PubMed1986

Hypotensive effect of Rhamnus lycioides extracts.

Intravenous administration of a lyophilized hot water extract and various organic solvent extracts of Rhamnus lycioides to normotensive anesthetized Wistar rats produced a lowering of systemic arterial blood pressure. Acute toxicity of the lyophilized extract was studied in mice by intraperitoneal injection. The phytochemical analyses revealed the presence of steroids-triterpenes, catechin tannins, flavonoids, sugars and resins.

Animals↗
PubMedDate not supplied

Antioxidant profile of mono- and dihydroxylated flavone derivatives in free radical generating systems.

A number of free radical generating systems were used to investigate the antioxidant properties and structure-activity relationships of a series of monohydroxylated and dihydroxylated flavones. Ortho-dihydroxylated flavones showed the highest inhibitory activity on enzymic and non-enzymic microsomal lipid peroxidation as well as on peroxyl radical scavenging. Most flavones were weak scavengers of hydroxyl radical, while ortho-dihydroxylated flavones interacted with superoxide anion generated by an enzymic system or by human neutrophils. This series of compounds did not exert cytotoxic effects on these cells. Scavenging of superoxide and peroxyl radicals may determine the antioxidant properties of these active flavones.

Animals↗