Biomedical subjects

F Bosch-Morell

Publications and source records attributed to F Bosch-Morell.

10 recordsLinked to original sources

PubMed1998

Experimental diabetic neuropathy: role of oxidative stress and mechanisms involved.

Oxidative stress has been related to the development of diabetic neuropathy. Experimental diabetes (alloxan injection of mice) promotes early biochemical changes in peripheral nervous tissue, e.g. decrease in Na,K-ATPase activity and glutathione (GSH) peroxidase (GSHPx) activity. The former decrease can be reverted by inhibiting protein kinase C (PKC), since it has been reported that PKC is activated in these experimental conditions. Here we present data demonstrating that the inhibition of PKC, as early as 4 days after alloxan administration, is not able to return to normal values GSHPx activity in sciatic nerve of diabetes mice. Thus, it would fit with our previous proposal of the possible glycation of this protein as an early event in experimental diabetes, and apparently rules out the control of GSHPx activity by PKC in this tissue.

Animals↗

PubMed1998

Serum malondialdehyde in HIV-seropositive children negatively correlates with CD4+ lymphocytes count.

Human immunodeficiency virus (HIV) infection is associated with oxidative stress as it has been demonstrated in adult-seropositive individuals. We show in this study that serum malondialdehyde (MDA) concentration of HIV-infected children was significantly higher than in control children. A negative correlation (r = -0.515) was found in HIV-infected children between their CD4+ lymphocyte count, and MDA concentration but not with serum antioxidant status. The increase of MDA concentration in HIV-seropositive children confirms the involvement of oxidative stress in the pathophysiology of this infection also in childhood. Because of the importance of oxidative stress and antioxidants for HIV viral replication, the adequacy of an adjuvant therapy with antioxidants should be considered; an adequate candidate for it could be N-acetylcysteine.

Biomarkers↗

PubMed1998

Serum malondialdehyde in HIV seropositive children.

Human immunodeficiency virus (HIV) infection is associated with oxidative stress as it has been demonstrated in adult seropositive individuals. We show in this study that serum malondialdehyde (MDA) concentration of HIV infected children was significantly higher than in control children. Moreover, a statistically significant decreased serum antioxidant status was detected in HIV infected children when compared with controls. No correlation was found in HIV infected children between their clinical or immunological categories, CD4+ lymphocyte count or CD4+/CD8+ ratio, and MDA concentration or serum antioxidant status. Newborn from HIV seropositive mothers had also a higher MDA concentration in cord blood serum than their corresponding controls from HIV seronegative mothers, whereas no difference could be established in the serum antioxidant status between both groups. No apparent correlation could be established between birth weight, gestational age or APGAR test values, and MDA in any of these groups. The results presented, (i.e., the increase of MDA concentration in HIV seropositive infants and children, and the decrease in serum total antioxidants in HIV seropositive children) confirm the involvement of oxidative stress in the pathophysiology of this infection also in childhood. Because of the importance of oxidative stress and antioxidants for HIV viral replication, the adequacy of an adjuvant therapy with antioxidants should be considered; an adequate candidate for it could be N-acetyl-cysteine.

Adolescent↗

PubMed1998

Chronic ethanol feeding induces cellular antioxidants decrease and oxidative stress in rat peripheral nerves. Effect of S-adenosyl-L-methionine and N-acetyl-L-cysteine.

Chronic ethanol feeding promotes oxidative stress in rat peripheral nerve. Malondialdehyde, a lipid peroxidation product, content increases in sciatic nerves of rats fed an ethanol-containing diet, when compared with pair-fed animals. Moreover, glutathione content and glutathione peroxidase activity in this same tissue decrease in ethanol-fed vs. pair-fed rats. S-Adenosyl-L-methionine and N-acetyl-L-cysteine, both with possible therapeutic action on alcoholism, were tested in this animal model. Only N-acetyl-L-cysteine was able to normalize malondialdehyde content and to restore glutathione content and glutathione peroxidase activity, to values not significantly different from those of sciatic nerves from pair-fed animals. The reasons for the different effect of both substances tested is also discussed.

Acetylcysteine↗

PubMed1998

Serum malondialdehyde: possible use for the clinical management of chronic hepatitis C patients.

Serum lipid peroxidation products are increased in inflammatory liver disease and, as we previously reported, also in chronic hepatitis C. We have performed a specific assay of malondialdehyde, the reported most abundant product of lipid peroxidation, in serum of twenty four chronic hepatitis C patients, before, during, and after interferon treatment. Liver biopsies were performed in each patient before and after interferon treatment. The results show higher serum malondialdehyde values in chronic hepatitis C patients than healthy subjects (n = 68) before interferon treatment (p < .001). Mean value of serum malondialdehyde levels after interferon treatment was significantly lower than before it (p < .002). Associating the histopathological findings in each of the 48 biopsies performed, with serum malondialdehyde and alanine aminotransferase activity levels, of the sample obtained the same day of biopsy, a much better correspondence with the histopathological severity was observed for malondialdehyde concentration than for alanine aminotransferase activity. These levels decreased significantly after interferon treatment. However, when the patients were grouped in responding (group I; n = 9) and non-responding (group II; n = 15) to interferon treatment, according to the histopathological findings before and after interferon, the values of group I before interferon treatment were significantly higher than group II (p < .03). Thus, a potential predictive value could be ascribed to the serum malondialdehyde levels before interferon treatment in these patients. We propose the utility of the specific assay of malondialdehyde for the clinical management of chronic hepatitis C patients.

Adult↗

PubMed1998

Lipid peroxidation products and antioxidants in human disease.

Lipid peroxidation (LPO) is a free radical-related process that in biologic systems may occur under enzymatic control, e.g., for the generation of lipid-derived inflammatory mediators, or nonenzymatically. This latter form is associated mostly with cellular damage as a result of oxidative stress, which also involves cellular antioxidants in this process. This article focuses on the relevance of two LPO products, malondialdehyde (MDA) and 4-hydroxynonenal (HNE), to the pathophysiology of human disease. The former has been studied in human serum samples of hepatitis C virus-infected adults and human immunodeficiency virus-infected children. In these two cases it is shown that the specific assay of serum MDA is useful for the clinical management of these patients. The presence of MDA in subretinal fluid of patients with retinal detachment suggests the involvement of oxidative stress in this process. Moreover, we were able to report the dependence of this involvement on the degree of myopia in these patients. The assay of MDA contents in the peripheral nerves of rats fed a chronic alcohol-containing diet or diabetic mice also confirms the pathophysiologic role of oxidative stress in these experimental models. In these two cases, associated with an increase in tissue LPO products content, we detected a decrease of glutathione peroxidase (GSHPx) activity in peripheral nerve, among other modifications. We have demonstrated that in vitro HNE is able to inhibit GSHPx activity in an apparent competitive manner, and that glutathione may partially protect and/or prevent this inactivation. The accumulation of LPO products in the brain of patients with Alzheimer's disease has also been described, and it is on the basis of this observation that we have tried to elucidate the role of oxidative stress and cellular antioxidants in beta-amyloid-induced apoptotic cell death of rat embryo neurons. Finally, we discuss the possible role of the observed vascular effects of HNE on human arteries.

Adult↗

PubMed1997

4-hydroxynonenal-induced relaxation of human mesenteric arteries.

The effect of 4-hydroxynonenal (4-HNE), a circulating lipid peroxidation product, on the vascular tone of human mesenteric arteries is studied. 4-HNE promotes relaxation of human mesenteric arterial rings in a concentration-dependent manner. Removal of the endothelium or treatment with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10(-4) M) partially prevented 4-HNE-induced relaxation, thus suggesting the intervention of nitric oxide from endothelial origin in the vascular effects of 4-HNE.

Adult↗

PubMed1996

Lipid peroxidation products in human subretinal fluid.

The concentrations of thiobarbituric acid reacting substances (TBARS) and proteins in the subretinal fluid (SF) of patients undergoing retinal detachment surgery have been determined. We have tried to establish the correlations between these biochemical and other clinical features of these patients: evolution time of the retinal detachment, age, degree of myopia, and macular affection. Caucasian patients, 19 men and 19 women (57.42 +/- 12.85 average age, interval 20-80) were randomly selected for this study. SF samples were obtained by puncture after scleral indentation. TBARS and protein concentrations were determined by the corresponding colorimetric assays. A linear correlation exists between TBARS and protein contents in these samples. No correlation could be established between evolution time of the retinal detachment and TBARS content in SF. TBARS in SF increases with increasing age in nonmyopic patients. In the samples of myopic patients the correlation was established between TBARS content and degree of myopia. The group of patients with more than 10 dioptres show a significant higher TBARS concentration in SF than any of the other groups studied. It can be concluded that lipid peroxidation products in SF originate, at least partially, from rod outer segments, and that lipid peroxidation is a process that might play a role in the pathogenesis of retinal detachment, specially in myopic patients.

Adult↗

PubMed1995

Phenytoin-induced glutathione depletion in rat peripheral nerve.

Administration of high doses (150-250 mg/kg body weight) of phenytoin (DPH) promote a 40% decrease in glutathione (GSH) content of rat sciatic nerve. This DPH-induced GSH depletion is accompanied with an electrophysiological impairment of peripheral neuromuscular function. H7 (20 mg/kg body weight IP, 30 min prior to DPH), a protein kinase C inhibitor, was able to prevent the DPH-induced GSH depletion only at the lower DPH dose used. This same inhibitor completely prevented the electrophysiological impairment at the lower DPH dose, and only partially at the higher DPH dose used. These results confirm the hypothesis of a DPH-dependent activation of PKC (that might be triggered by, or be the consequence of, the reduction of the intracellular antioxidant GSH), as one of the pathophysiological mechanisms involved in DPH-induced neurotoxicity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1994

4-Hydroxynonenal, a lipid peroxidation product, induces relaxation of human cerebral arteries.

The relaxant effect of 4-hydroxynonenal (4-HNE), a lipid peroxidation product, on human cerebral arteries was studied. Addition of 4-HNE to artery rings promoted no contraction, and after stimulation with prostaglandin F2 alpha (PFG2 alpha; 10(-7)-3 x 10(-6) M), 100% relaxation was obtained with 3 x 10(-5) M 4-HNE. Inhibition of nitric oxide formation with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME; (10(-4) M), as well as prostaglandin synthesis with indomethacin (3 x 10(-6) M), partially prevented 4-HNE-induced relaxation, but each of these substances separately failed to inhibit complete relaxation. Addition of both inhibitors together reduced 4-HNE-induced relaxation to approximately 50%, but relaxation could not be abolished. When the endothelium was removed, 4-HNE did not promote relaxation after PGF2 alpha stimulation. The possible roles of different intracellular signaling systems in the vascular effect of 4-HNE are discussed.

Aged↗