Protective role of dehydroascorbate in rat liver ischemia-reperfusion injury

BACKGROUND: Oxidative stress plays an important role in liver ischemia/reperfusion (I/R) injury. Thus, enhancing the liver antioxidant capacity could be a promising therapeutic strategy. Ascorbate (AA) is considered the perfect antioxidant, but its therapeutic efficacy is greatly limited by its slow achievement of high intracellular levels. This might be circumvented by administering dehydroascorbate (DHA), which presents a several-fold greater uptake than AA, and undergoes rapid intracellular reduction to AA. Thus, our aim was to assess the protective role of DHA in liver I/R injury. MATERIALS AND METHODS: Wistar rats (200-300 g bw) were pretreated iv with different doses of AA or DHA 20 min before liver ischemia, followed by 6 h reperfusion. Liver damage was assessed by biochemical and morphological indices. RESULTS: DHA pretreatment induced a rapid increase in liver ascorbate levels, significantly higher than findings for AA, without any significant reduction in glutathione levels. Liver damage during I/R in controls showed significant increases in serum transaminases and hepatic thiobarbituric acid reactive substances with alterations of liver morphology. DHA administration induced a clear, significant protection against I/R injury, whereas liver damage was only moderately prevented by AA. CONCLUSIONS: DHA might represent a simple, effective therapeutic option to prevent liver damage associated with ischemia/reperfusion

Antioxidant capacity and protein oxidation in cerebrospinal fluid of amyotrophic lateral sclerosis.

Background The causes of Amyotrophic Lateral Sclerosis (ALS) are unknown. A bulk of evidence supports the hypothesis that oxidative stress and mitochondrial dysfunction can be implicated in ALS pathogenesis. Methods We assessed, in cerebrospinal fluid (CSF) and in plasma of 49 ALS patients and 8 controls, the amount of oxidized proteins (AOPP, advanced oxidation protein products), the total antioxidant capacity (FRA, the ferric reducing ability), and, in CSF, two oxidation products, the 4-hydroxynonenal and the sum of nitrites plus nitrates. Results The FRA was decreased (p = 0.003) in CSF, and AOPP were increased in both CSF (p = 0.0039) and plasma (p = 0.001) of ALS patients. The content of AOPP was differently represented in CSF of ALS clinical subsets, resulting in increase in the common and pseudopolyneuropathic forms (p < 0.001) and nearly undetectable in the bulbar form, as in controls. The sum of nitrites plus nitrates and 4-hydroxynonenal were unchanged in ALS patients compared with controls. Conclusion Our results, while confirming the occurrence of oxidative stress in ALS, indicate how its effects can be stratified and therefore implicated differently in the pathogenesis of different clinical forms of ALS

Biological effects of PEMF (pulsing electromagnetic field): an attempt to modify cell resistance to anticancer agents.

Pulsing Electromagnetic Field (PEMF) effects lead to a modification of the multidrug resistance (MDR) of cells in vitro and in vivo. The murine leukemic doxorubicin-resistant cell line, P388/Dx, subjected to PEMF irradiation in vitro, showed a significant difference in thymidine incorporation when the concentration of doxorubicin reached a level of 1 microgram/mL, which corresponds to the inhibition dose 50 (ID50). The human lymphoblastic leukemia vinblastine-resistant cell line, CEM/VLB100, also showed a significant modification under the same experimental conditions at the in vitro ID50 corresponding to a vinblastine concentration of 100 ng/mL. BDF1 mice transplanted with P388/Dx cells also had an increase in their life span when doxorubicin was injected intraperitoneally in fractionated doses, while being subjected to PEMF irradiation

Role of matrix metalloproteinases and their tissue inhibitors as potential biomarkers of left ventricular remodelling in the athlete's heart

International audienceThe aim of the present study was to verify whether plasma MMPs and TIMPs could be used as potential markers of paraphysiological remodelling in the athlete's heart, and to correlate these matrix parameters with echocardiographic signs of left ventricular remodelling. Plasma MMP-2 and MMP-9 were measured by zymography, TIMP-1 and TIMP-2 were measured by ELISA in 42 veteran marathoners (AH), and in 25 sedentary healthy subjects (CTL). All subjects were submitted to clinical examination and 2D color Doppler echocardiography together with the measure of circulating NT-proBNP; GGT was evaluated as a marker of cardiovascular disease. Veteran athletes had significant elevation in LV dimensions and calculated LV mass index. Diastolic and systolic functions were normal for both groups. MMP-9 levels were significantly lower in AH than in CTL (56.9±4.3 versus 119.4±21.5 mU/l, p<0.01). There were significant differences in MMP2 between the 2 groups,with down-regulation in the AH (182.5±16.8 U/ml in CTL versus 117.1±9.1 in AH, p<0.01). MMP-2 and MMP-2/TIMP-2 were inversely correlated to myocardial indices of hypertrophy in AH and CTL. AH and CTL subjects showed similar TIMPs values. Our results indicate that MMPs and TIMPs could represent potential biomarkers of adaptive heart remodelling in the athletes. In addition, the inverse correlation of the MMP-2/TIMP-2 system with echocardiographic signs of myocardial hypertrophy could represent a new diagnostic and prognostic indicator useful in the evaluation of cardiovascular risk in athletes

Role of matrix metalloproteinases and their tissue inhibitors as potential biomarkers of left ventricular remodelling in the athlete’s heart

The aim of the present study was to verify whether plasma MMPs (matrix metalloproteinases) and TIMPs (tissue inhibitors of MMPs) could be used as potential markers of paraphysiological remodelling in the athlete’s heart, and to correlate these matrix parameters with echocardiographic signs of LV (left ventricular) remodelling. Plasma MMP-2 and MMP-9 were measured by zymography, and TIMP-1 and TIMP-2 were measured by ELISA in 42 veteran marathoners with AH (athlete’s heart), and in 25 sedentary healthy subjects (CTL). All subjects were submitted to a clinical examination and two-dimensional colour Doppler echocardiography together with the measurement of circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide); GGT (γ-glutamyl transpeptidase) was evaluated as a marker of cardiovascular disease. Veteran athletes had a significant elevation in LV dimensions and calculated LV mass index. Diastolic and systolic functions were normal for both groups. MMP-9 levels were significantly lower in AH than in CTL subjects (56.9±4.3 compared with 119.4±21.5 m-units/l, P&lt;0.01). There were significant differences in MMP-2 between the two groups, with a down-regulation in the AH subjects (182.5±16.8~units/ml in CTL compared with 117.1±9.1~units/ml in AH, P&lt;0.01). MMP-2 and MMP-2/TIMP-2 were inversely correlated with myocardial indices of hypertrophy in AH and CTL subjects. AH and CTL subjects showed similar TIMP values. The results of the present study indicate that MMPs and TIMPs could represent potential biomarkers of adaptive heart remodelling in the athletes. In addition, the inverse correlation of the MMP-2/TIMP-2 system with echocardiographic signs of myocardial hypertrophy could represent a new diagnostic and prognostic indicator useful in the evaluation of cardiovascular risk in athletes. Abbreviations: A, late diastolic peak velocity; AH, athlete’s heart; CTL, control; E, early diastolic peak velocity; ECM, extracellular matrix; EF, ejection fraction; GGT, γ-glutamyl transpeptidase; HF, heart failure; LV, left ventricular; LVEDD, LV end-diastolic diameter; LVM, LV mass; MMP, matrix metalloproteinase; NT-proBNP, N-terminal pro-B-type natriuretic peptide; TIMP, tissue inhibitor of MMP

DETECTION OF SALIVARY ANTIBODIES IN CATS INFECTED WITH FELINE IMMUNODEFICIENCY VIRUS

The saliva of cats infected with feline immunodeficiency virus was examined for total immunoglobulin content and antiviral antibodies. Seropositive cats showed an increase in salivary immunoglobulin G levels, which was only partly attributable to the enhanced prevalence of oral inflammatory lesions, compared with the levels in seronegative cats. Immunoglobulin G, but not immunoglobulin M, levels in serum were also increased. Salivary antibodies were determined by indirect immunofluorescence and Western blot (immunoblot) analysis. All but 1 of the 16 seropositive cats examined were positive, while all 16 control cats were negative. The presence of oral lesions was not a prerequisite for antibody detection in saliva. It was concluded that salivary antibody might be usefully exploited for diagnostic and epidemiologic purposes