Publications (15)38.96 Total impact
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Article: Ozone oxidative post-conditioning in acute renal failure.
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ABSTRACT: The ischaemia-reperfusion process is largely mediated by reactive oxygen species. Taking into account that a transient and controlled administration of ozone is able to upregulate cellular antioxidant enzymes, a morphological, biochemical and functional renal study was performed in rats undergoing warm renal ischaemia. Rats were divided into four groups. All except the negative controls underwent 60 min' bilateral renal ischaemia followed by 10 days' reperfusion. The positive control group received no further treatment. The ozone group received an ozone/oxygen mixture (ozone dose 0.5 mg/kg) immediately after the ischaemia and daily for the 10 days' reperfusion; the oxygen group were given the same concentration of oxygen alone (13 mg/kg). Biochemical parameters fructosamine, phospholipase A2, catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured, as well as renal plasma flow and glomerular filtration rate. Renal plasma flow and glomerular filtration rate decreased significantly in the positive controls and the oxygen group whereas values in the ozone group were similar to those in the negative control group. With respect to the biochemical parameters, ozone maintained a homeostasis redox, with significant increases in catalase and superoxide dismutase activities and similar values for phospholipase A2 and fructosamine compared with the negative control group. Fewer morphological alterations were seen in kidneys from the ozone group. No advantages were obtained in the positive control and oxygen groups. The protective effect of ozone may be explained by upregulation of the antioxidant defence system and beneficial effects on blood circulation and in oxygen metabolism. Ozone treatment may represent a therapeutic approach for minimising renal damage after transplantation.Journal of Pharmacy and Pharmacology 03/2009; 61(2):221-7. · 2.17 Impact Factor -
Article: Kinetics of monoclonal anti-epidermal growth factor receptor antibody (IOR EGF/r3)-induced apoptosis in human carcinoma bearing nude mice.
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ABSTRACT: Apoptosis seems to play an important role in cancer immunotherapy outcome. We have studied the kinetic pattern of apoptosis induction in H125 human lung carcinoma xenografts after treatment with the monoclonal antibody (MAb) anti-epidermal growth factor receptor (EGFr) IOR EGF/r3. Tumor-bearing nude mice were injected intravenously with a single 8 mg/kg dose of IOR EGF/r3 and tumor specimens were taken up to 30 days post treatment. Apoptosis was measured by morphometric analysis of the histological sections at each tumor specimen over time points. The results showed a significant apoptotic response in tumors within six days after injection of this MAb reaching a peak at 20 days post treatment. The kinetics were very broad, with apoptotic cells present over the entire time-frame. However, the time course of the apoptotic index showed a significant difference to the mitotic index. Finally, the MAb-induced apoptosis was related to tumor growth delay indicating a probable arrest of cell cycle and a corresponding inhibition of tumor progression, which was corroborated by the Ki67 and proliferating cell nuclear antigen (PCNA) biomarkers.Puerto Rico health sciences journal 04/2008; 27(1):35-41. · 0.56 Impact Factor -
Article: Antioxidant mechanism is involved in the gastroprotective effects of ozonized sunflower oil in ethanol-induced ulcers in rats.
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ABSTRACT: This research was performed in order to determine the potential protective effects of ozonized sunflower oil (OSO) in the injury of rat gastric mucosa induced by absolute ethanol and as well as to elucidate the role of reactive oxygen species (ROS), lipid peroxidation, and some important constituents of antioxidant defense such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in these effects. OSO was administered to rats intragastrically by a cannula and it was applied during four days to animals. The doses of OSO administered daily to each group of rats were 4, 12, and 24 mg/kg, respectively, and one hour after the last treatment, absolute ethanol (1 mL/200 mg body weight) was administered. Our results showed that gastric ulcer index was significantly reduced in rats pretreated with OSO as compared with ethanol-treated controls. However, in rats pretreated with OSO, no significant reduction of TBARS content in gastric mucosa was found as compared to those rats treated with ethanol alone. In contrast, SOD and GSH-Px activities were significantly increased in gastric mucosa of OSO-pretreated rats with respect to those treated with ethanol alone. In summary, our results demonstrate that OSO pretreatment exerts protective effects in ethanol-induced gastric ulcers in rats. Furthermore, these results provide evidence that these protective effects of OSO are mediated at least partially by stimulation of some important antioxidant enzymes such as SOD and GSH-Px, which are scavengers of ROS and therefore prevent gastric injury induced by them.Mediators of Inflammation 02/2007; 2007:65873. · 3.26 Impact Factor -
Article: Ubiquitous expression of human SCA2 gene under the regulation of the SCA2 self promoter cause specific Purkinje cell degeneration in transgenic mice.
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ABSTRACT: The objective of this work was the generation of an animal model of the SCA2 disease for future studies on the benefits of therapeutic molecules and neuropathological mechanisms that underline this human disorder. The transgenic fragment was microinjected into pronuclei of B6D2F1 X OF1 mouse hybrid strain. For Northern blots, RNAs were hybridized with a human cDNA fragment from the SCA2 gene and a mouse beta-actin cDNA fragment. Monoclonal antibody directed to the N-terminal of the ataxin 2 protein with 22Q was used for Western blot analysis. A rotating rod apparatus was utilized to measure motor coordination of mice. Immunohistochemical detection of Purkinje neurons was performed with anti-calbindin 28K as primary antibody. Ubiquitous expression of the SCA2 transgene with 75 CAG repeats regulated by the SCA2 self promoter was obtained after generation of our transgenic mice. Analysis of transgenic mice revealed significant differences of motor coordination compared with the wild type littermates. Specific degeneration of Purkinje neurons and transgene over-expression in the brain, liver and skeletal muscle, rather than in lungs and kidneys was also observed, resembling the expression pattern of the ataxin 2 in humans.Neuroscience Letters 02/2006; 392(3):202-6. · 2.11 Impact Factor -
Article: Hepatoprotective effects of propolis extract on paracetamol‐induced liver damage in mice
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ABSTRACT: The effects of propolis extract were studied in a model of acute hepatotoxicity induced by a high oral dose (600 mg/kg) of paracetamol in mice. Propolis at doses of 25, 50 and 100 mg/kg i.p. decreased significantly the activity of alanine aminotransierase in serum, which was increased by paracetamol alone and increased the concentration of reduced glutathione in mouse liver, which is depleted by paracetamol. Propolis extract also reduced liver damage induced by paracetamol in mice, which was observed by optical and electron microscopy. The hepatoprotective effects of propolis were produced when administered 30 min before paracetamol or 2 h after it. It is concluded that propolis exerts some effects which resemble those of N-acetylcysteine, the well-known antidote of paracetamol.Phytotherapy Research 01/2006; 8(4):229 - 232. · 2.09 Impact Factor -
Article: Lipid peroxides and antioxidant enzymes in cisplatin-induced chronic nephrotoxicity in rats.
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ABSTRACT: Cisplatin (CDDP), an anticancer drug, induces remarkable toxicity in the kidneys of animals and humans and it has been well documented that reactive oxygen species and the renal antioxidant system are strongly involved in acute renal damage induced by CDDP. The aim of the present study was to investigate whether or not the renal antioxidant system plays also an important role in chronic renal damage induced by repeated doses of CDDP (1 mg/kg intraperitoneally twice weekly during 10 weeks in rats). In order to elucidate it, serum creatinine and urea levels, renal glutathione and thiobarbituric acid-reactive substances (TBARS) content, as well as renal superoxide dismutase and glutathione peroxidase activities were measured in the kidney homogenates of chronically CDDP-treated rats and additionally histological studies were performed in the rat kidneys. The chronic treatment with CDDP induced a significant increase in creatinine and urea levels in serum, but the other parameters mentioned above were not significantly modified as compared to the values in nontreated rats. Taking into account these results, we conclude that chronic CDDP administration induces also severe nephrotoxicity, in contrast to CDDP acute application, without any significant modification in the activity of relevant antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, renal glutathione and lipid peroxides, by which the role of the antioxidant system in chronic nephrotoxicity induced by CDDP in rats is uncertain.Mediators of Inflammation 09/2005; 2005(3):139-43. · 3.26 Impact Factor -
Article: Methylglyoxal administration induces diabetes-like microvascular changes and perturbs the healing process of cutaneous wounds.
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ABSTRACT: Increased formation of MG (methylglyoxal) and related protein glycation in diabetes has been linked to the development of diabetic vascular complications. Diabetes is also associated with impaired wound healing. In the present study, we investigated if prolonged exposure of rats to MG (50-75 mg/kg of body weight) induced impairment of wound healing and diabetes-like vascular damage. MG treatment arrested growth, increased serum creatinine, induced hypercholesterolaemia (all P < 0.05) and impaired vasodilation (P < 0.01) compared with saline controls. Degenerative changes in cutaneous microvessels with loss of endothelial cells, basement membrane thickening and luminal occlusion were also detected. Acute granulation appeared immature (P < 0.01) and was associated with an impaired infiltration of regenerative cells with reduced proliferative rates (P < 0.01). Immunohistochemical staining indicated the presence of AGEs (advanced glycation end-products) in vascular structures, cutaneous tissue and peripheral nerve fibres. Expression of RAGE (receptor for AGEs) appeared to be increased in the cutaneous vasculature. There were also pro-inflammatory and profibrotic responses, including increased IL-1beta (interleukin-1beta) expression in intact epidermis, TNF-alpha (tumour necrosis factor-alpha) in regions of angiogenesis, CTGF (connective tissue growth factor) in medial layers of arteries, and TGF-beta (transforming growth factor-beta) in glomerular tufts, tubular epithelial cells and interstitial endothelial cells. We conclude that exposure to increased MG in vivo is associated with the onset of microvascular damage and other diabetes-like complications within a normoglycaemic context.Clinical Science 07/2005; 109(1):83-95. · 4.61 Impact Factor -
Article: Role of protein synthesis in the protection conferred by ozone-oxidative-preconditioning in hepatic ischaemia/reperfusion.
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ABSTRACT: The liver is damaged by sustained ischaemia during liver transplantation, and the reperfusion after ischaemia results in further functional impairment. Ozone oxidative preconditioning (OzoneOP) protected the liver against ischaemia/reperfusion (I/R) injury through different mechanisms. The aim of this study was to investigate the influence of the inhibition of protein synthesis on the protective actions conferred by OzoneOP in hepatic I/R. Rats were treated with cycloheximide (CHX) in order to promote protein synthesis inhibition after OzoneOP treatment. Plasma transaminases, malondialdehyde and 4-hydroxyalkenals and morphological characteristics were measured as an index of hepatocellular damage; Cu/Zn-superoxide dismutase (SOD), Mn-SOD, catalase, total hydroperoxides and glutathione levels as markers of endogenous antioxidant system. OzoneOP increased Mn-SOD isoform and ameliorated mitochondrial damage. CHX abrogated the protection conferred by OzonoOP and decreased Mn-SOD activity. Cellular redox balance disappeared when CHX was introduced. Protein synthesis is involved in the protective mechanisms mediated by OzoneOP. Ozone treatment preserved mitochondrial functions and cellular redox balance.Transplant International 06/2005; 18(5):604-12. · 2.92 Impact Factor -
Article: Immunohistochemical recognition of the epidermal growth factor receptor by the h-R3 antibody in the skin of experimental animals.
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ABSTRACT: The h-R3 is a humanized monoclonal antibody (Mab) that binds to the external domain of the human epidermal growth factor receptor (EGF-R). It has being used for the treatment of head and neck tumors. Since it is known that different animal species have different EGF-R amino acid sequences, it raises the handicap that, a priori, the animal species relevant for the pharmacodynamic, pharmacokinetic, and toxicologic studies of this Mab are unknown. To elucidate relevant laboratory animal species, the authors investigated the immunohistochemical recognition by h-R3 Mab of EGF-R in small skin biopsy samples obtained from NMRI nu/nu, C57Bl/6, and OF-1 mice; Sprague-Dawley rats; Hartley guinea pigs; New Zealand rabbits; and Cercopithecus aethiops and Macaca fascicularis monkeys. Additionally, three human skin biopsies were obtained from trauma victims. The immunolocalization of EGF-R in different tissue sections was performed using the avidin-biotin peroxidase complex (ABC) technique. The skin sections from different tissues were tested with the biotinylated h-R3 Mab or with a biotinylated irrelevant Mab, used as negative control. The staining intensity was qualified as:-, no staining; +, weak staining; ++, moderate staining; +++, strong staining. Macaca fascicularis monkey, New Zealand rabbit, and OF-1 mouse skins had a strong staining intensity; Cercopithecus aethiops monkey and Sprague-Dawley rat skins showed a moderate to strong staining intensity; C57Bl/6 mouse skins showed a moderate staining intensity. No staining was observed in the skins from Hartley guinea pigs and MNRI nu/nu mice. The fact that h-R3 Mab recognizes other animal EGF receptors in addition to the human EGF-R makes it possible to perform relevant pharmacodynamic, pharmacokinetic, and toxicologic studies in some laboratory animals.Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 12/2004; 12(4):360-3. · 1.63 Impact Factor -
Article: Delayed treatment with nimesulide reduces measures of oxidative stress following global ischemic brain injury in gerbils.
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ABSTRACT: Metabolism of arachidonic acid by cyclooxygenase is one of the primary sources of reactive oxygen species in the ischemic brain. Neuronal overexpression of cyclooxygenase-2 has recently been shown to contribute to neurodegeneration following ischemic injury. In the present study, we examined the possibility that the neuroprotective effects of the cyclooxygenase-2 inhibitor nimesulide would depend upon reduction of oxidative stress following cerebral ischemia. Gerbils were subjected to 5 min of transient global cerebral ischemia followed by 48 h of reperfusion and markers of oxidative stress were measured in hippocampus of gerbils receiving vehicle or nimesulide treatment at three different clinically relevant doses (3, 6 or 12 mg/kg). Compared with vehicle, nimesulide significantly (P<0.05) reduced hippocampal glutathione depletion and lipid peroxidation, as assessed by the levels of malondialdehyde (MDA), 4-hydroxy-alkenals (4-HDA) and lipid hydroperoxides levels, even when the treatment was delayed until 6 h after ischemia. Biochemical evidences of nimesulide neuroprotection were supported by histofluorescence findings using the novel marker of neuronal degeneration Fluoro-Jade B. Few Fluoro-Jade B positive cells were seen in CA1 region of hippocampus in ischemic animals treated with nimesulide compared with vehicle. These results suggest that nimesulide may protect neurons by attenuating oxidative stress and reperfusion injury following the ischemic insult with a wide therapeutic window of protection.Neuroscience Research 10/2003; 47(2):245-53. · 2.25 Impact Factor -
Article: Ischemic and Ozone Oxidative Preconditioning in the Protection Against Hepatic Ischemic-Reperfusion Injury
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ABSTRACT: It has been demonstrated that ozone, probably through a mechanism of oxidative preconditioning (OP), protected the liver against the damage mediated by reactive oxygen species. Taking into account that iscehmic preconditioning (IschP) is also a protective mechanism, a comparative study between both preconditioning settings was performed in order to study the effectiveness of both protective procedures. Rats were randomly divided into 4 groups: 1- control, sham operated (anesthesia and laparotomy plus surgical manipulation); 2- I/R (ischemia for 90 min followed by 90 min reperfusion); 3- Ischp+I/R, as group 2 but submitted to a previous ischemic preconditioning (ischemia 10 min and reperfusion 10 min); 4- OzoneOP+I/R, as group 2 but submitted to a pervious oxidative preconditioning with 15 sessions, daily, of ozone by rectal administration (dose of 1 mg/kg). The comparison between both preconditionings showed no biochemical differences for the parameters evaluated. Nevertheless, the histological study demonstrated that the protective effect produced by the OzoneOP is superior to that achieved with the IschP.Ozone Science and Engineering 06/2003; 25(3):241-250. · 1.15 Impact Factor -
Article: Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia.
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ABSTRACT: Cyclooxygenase-2 is involved in the inflammatory component of the ischemic cascade, playing an important role in the delayed progression of the brain damage. The present study evaluated the pharmacological effects of the selective cyclooxygenase-2 inhibitor nimesulide on delayed neuronal death of hippocampal CA1 neurons following transient global cerebral ischemia in gerbils. Administration of therapeutically relevant doses of nimesulide (3, 6 and 12 mg/kg; i.p.) 30 min before ischemia and at 6, 12, 24, 48 and 72 h after ischemia significantly (P<0.01) reduced hippocampal neuronal damage. Treatment with a single dose of nimesulide given 30 min before ischemia also resulted in a significant increase in the number of healthy neurons in the hippocampal CA1 sector 7 days after ischemia. Of interest is the finding that nimesulide rescued CA1 pyramidal neurons from ischemic death even when treatment was delayed until 24 h after ischemia (34+/-9% protection). Neuroprotective effect of nimesulide is still evident 30 days after the ischemic episode, providing the first experimental evidence that cyclooxygenase-2 inhibitors confer a long-lasting neuroprotection. Oral administration of nimesulide was also able to significantly reduce brain damage, suggesting that protective effects are independent of the route of administration. The present study confirms the ability of cyclooxygenase-2 inhibitors to reduce brain damage induced by cerebral ischemia and indicates that nimesulide can provide protection when administered for up to 24 h post-ischemia.European Journal of Pharmacology 10/2002; 453(2-3):189-95. · 2.52 Impact Factor -
Article: Inhibitory effects of Spirulina in zymosan-induced arthritis in mice.
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ABSTRACT: The anti-inflammatory effect of microalgae Spirulina was studied in zymosan-induced arthritis in mice. Four days after the intra-articular injection of zymosan (15 mg/ml), Spirulina (100 and 400 mg/kg perorally) was administered to animals for 8 days. The mice were than killed and beta-glucuronidase was measured in the synovial fluid. Each knee joint was totally removed for histopathological studies. Spirulina significantly reduced the levels of beta-glucuronidase that had been increased by zymosan. Histopathological and ultrastructural studies showed inhibition of the inflammatory reaction, whereas no destruction of cartilage, well-preserved chondrocytes, and normal rough endoplasmic reticulum and mitochondria were seen. The anti-arthritic effect exerted by Spirulina as shown in this model may be at least partly due to the previously reported antiinflammatory and antioxidative properties of its constituent, phycocyanin. To our knowledge, this is the first report on the anti-inflammatory effect of Spirulina in an experimental model of arthritis.Mediators of Inflammation 05/2002; 11(2):75-9. · 3.26 Impact Factor -
Article: Similar protective effect of ischaemic and ozone oxidative preconditionings in liver ischaemia/reperfusion injury.
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ABSTRACT: Many studies indicate that oxygen free-radical formation after reoxygenation of liver may initiate the cascade of hepatocellular injury. It has been demonstrated that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by reactive oxygen species (ROS) and protecting against liver ischaemia-reperfusion (I/R) injury. On the basis of those results we postulated that ozone treatment in our experimental conditions has biochemical parameters similar to the ischaemic preconditioning (IscheP) mechanism. Four groups of rats were classified as follows: (1) sham-operated animals subjected to anaesthesia and laparotomy, plus surgical manipulation; (2) I/R animals were subjected to 90 min of right-lobe hepatic ischaemia, followed by 90 min of reperfusion; (3) IscheP, previous to the I/R period (as in group 2): animals were subjected to 10 min of ischaemia and 10 min of reperfusion; (4) ozone oxidative preconditioning (OzoneOP), previous to the I/R period (as in group 2): animals were treated with ozone by rectal insufflation 1 mg kg (-1). The rats received 15 ozone treatments, one per day, of 5-5.5 ml at the ozone concentration of 50 microg ml (-1). The following parameters were measured: serum transaminases (AST, ALT) and 5'-nucleotidase (5 '-NT), with morphological determinations, as indicators or hepatocellular injury; total sulfhydryl groups, calcium levels and calpain activity as mediators which take part in xanthine deshydrogenase (XDH) conversion to xanthine oxidase (XO) (reversible and irreversible forms, respectively); XO activities and malondialdehyde + 4-hydroyalkenals as indicators of increased oxidative stress. AST, ALT levels were attenuated in the IscheP (130 +/- 11.4 and 75 +/- 5.7 U l (-1)) with regard to the I/R group (200 +/- 22 and 117 +/- 21.7 U l (-1)) while the OzoneOP maintained both of the enzyme activities ( 89.5 +/- 12.6 and 43.7 +/- 10 U l (-1)) without statistical differences (P< 0.05) in comparison with the sham-operated ( 63.95 +/- 11 and 19.48 +/- 3.2 U l (-1)). Protective effects of both the preconditioning settings on the preservation of total sylfhydryl groups (IscheP: 6.28 +/- 0.07, OzoneOP: 6.34 +/- 0.07 micromol mg prot (-1)), calcium concentrations (IscheP: 0.18 +/- 0.09, OzoneOP: 0.20 +/- 0.06 micromol mg prot (-1)), and calpain activity (IscheP: 1.04 +/- 0.58, OzoneOP: 1.41 +/- 0.79 U mg prot (-1)) were observed. Both of the preconditionings attenuated the increase of total XO associated to I/R injury. Generation of malondialdehyde + 4 hydroxyalkenals was prevented by IscheP and OzoneOP without statistical differences between the two protective procedures. These results provide evidence that both of the preconditioning settings share similar biochemical mechanisms of protection in the parameters which were measured. Although there were no differences from a biochemical point of view between Ischaemic and OzoneOPs, the histological results showed a more effective protection of OzoneOP than IscheP in our experimental conditions.Pharmacological Research 04/2002; 45(4):333-9. · 4.44 Impact Factor -
Article: The highly selective cyclooxygenase-2 inhibitor DFU is neuroprotective when given several hours after transient cerebral ischemia in gerbils.
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ABSTRACT: Several studies suggest that cyclooxygenase-2 contributes to the delayed progression of ischemic brain damage. In this study we examined whether the highly selective cyclooxygenase-2 inhibitor DFU reduces neuronal damage when administered several hours after 5 min of transient forebrain ischemia in gerbils. The extent of ischemic injury was assessed behaviorally by measuring the increases in locomotor activity and by histopathological evaluation of the extent of CA1 hippocampal pyramidal cell injury 7 days after ischemia. DFU treatment (10 mg/kg, p.o.) significantly reduced hippocampal neuronal damage even if the treatment is delayed until 12 h after ischemia. These results suggest that selective cyclooxygenase-2 inhibitors may be a valuable therapeutic strategy for ischemic brain injury.Brain Research 03/2002; 927(2):212-5. · 2.73 Impact Factor
Top co-authors
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2003
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Ministerio de Salud Pública, Cuba
Havana, Provincia de La Habana, Cuba -
University of Havana
Havana, Provincia de La Habana, Cuba
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