PubMed Health⌕ Search

Biomedical subjects

J C Perazzo

Publications and source records attributed to J C Perazzo.

At least 19 recordsLinked to original sources
PubMed2006

Influence of fasting on the effects of dimethylamiloride and oxfenicine on ischaemic-reperfused rat hearts.

To assess whether glycolysis, Na+-H+ exchange and oxidation of fatty acid derived from endogenous lipolysis are involved in the beneficial effects of 24-h fasting on the ischaemic - reperfused heart, it was studied the effects of inhibiting Na+ - H+ exchange using 10 muM dimethylamiloride and fatty acid oxidation using 2 mM oxfenicine, on the functional activity, lactate production and cell viability measured with tetrazolium stain. Since fasting accelerates heart fatty acid oxidation, data were compared to those from fed rats; using Langendorff perfused (glucose 10 mM) hearts of 250-350 g Wistar rats exposed to 25 min ischaemia - 30 min reperfusion. Fasting reduced the ischaemic rise of end diastolic pressure (contracture), improved recovery of contraction and lowered lactate production in comparison with the fed whereas cellular viability was similar in both groups. Dimethylamiloride improved the recovery of contraction (fed control 24 +/- 9%, fed treated 68 +/- 11%, P < 0.05 at the end of reperfusion), attenuated the contracture (fed control 40 +/- 9%, fed treated 24 +/- 11%, P < 0.05 at the beginning of reperfusion) and reduced lactate production in the fed group and increased cellular viability in both groups (fed control 21 +/- 6%, fed treated 69 +/- 7%, P < 0.05, and fasted control 18 +/- 7%, fasted treated 53 +/- 8%, P < 0.05). Oxfenicine reduced the recovery of contraction (fasted control 88 +/- 6%, fasted treated 60 +/- 11%, P < 0.05) and increased lactate production of fasted group and attenuated the contracture in the fed. These data suggest that beneficial effects of fasting owe, at least in part, to a lowered glycolysis probably secondary to the increased fatty acid oxidation and to the accumulation of energy supplying acyl esters. Dimethylamiloride slowing of glycolysis might explain functional improvement, whereas it seems unrelated to the protection on cell viability.

Amiloride↗
PubMed2005

Effects of 5-hydroxydecanoate and ischemic preconditioning on the ischemic-reperfused heart of fed and fasted rats.

This investigation aimed to assess whether the mitochondrial ATP-sensitive potassium channel blocker 5-hydroxydecanoate (5-HD) could abolish the protection conferred by fasting and ischemic preconditioning (IPC) and to ascertain whether these effects are associated with glycogen breakdown and glycolytic activity. Langendorff perfused hearts of fed and 24-h fasted rats were exposed to 25 min ischemia plus 30 min reperfusion. IPC was achieved by a 3 min ischemia plus a 5 min reperfusion cycle. 5-HD (100 microM) perfusion begun 5 min before IPC or 13 min before sustained ischemia in the non preconditioned groups. Fasting improved the reperfusion recovery of contraction, decreased the contracture and the lactate production, increased glycogenolysis and did not affect the percentage of viable tissue. 5-HD abolished the effects of fasting on the contractile recovery but did not affect the contracture. 5-HD decreased the lactate production in the fed group, increased the preischemic glycogen content in both nutritional groups and did not affect the ischemic glycogen fall. IPC improved the contractile function but prevented the contracture only in the fed group, reduced lactate accumulation and glycogenolysis and evoked an increase of the viable tissue. 5-HD abolished the effects of IPC on the contractile recovery and did not affect its effect on the contracture, lactate production, glycogenolysis and viable tissue. These data suggest that the mitocondrial ATP-sensitive potassium channel is involved in the effects of fasting and IPC on the contractile function but the other cardioprotective and metabolic effects appear evoked through other mechanisms. Also suggest that besides the inhibition of the mitochondrial potassium channel, other mechanisms mediate the effects of 5-HD.

Animals↗
PubMed2004

Influence of fasting on the effects of diazoxide in the ischemic-reperfused rat heart.

This investigation aimed to assess whether the mitochondrial ATP-sensitive potassium channel opener diazoxide could reproduce the protection conferred by ischemic preconditioning and to ascertain whether its effects are associated with changes in glycogen breakdown and glycolytic activity. Hearts of fed and 24-h fasted rats were perfused with 10 mM glucose containing medium and exposed to 25 min no-flow ischemia plus 30 min reperfusion. Diazoxide (10 microM) perfusion was begun 10 min before ischemia and continued throughout the experiment. Fasting accelerated reperfusion recovery of contraction, reduced the post-ischemic contracture and decreased lactate accumulation during ischemia but had no effects on glycogen levels and cellular viability. Diazoxide, did not affect glycogen catabolism but improved reperfusion recovery of contraction. Furthermore, diazoxide reduced ischemic lactate accumulation and contracture amplitude only in the fed group whereas it improved cell viability in the fed and fasted groups. These data indicate that: 1) reduced lactate production which may attenuate myocyte acidification might explain, at least in part, the beneficial effects of diazoxide on mechanical function, although data obtained with the fasted rat hearts indicate that other mechanisms must be involved as well; 2) the reduction of lactate production occurring in the fed group, does not seem to be related to glycogenolysis; and 3) since diazoxide improved cell viability in the fasted rat group where it did not reduce glycolytic activity, other mechanisms may be responsible for this cytoprotective effect.

Animals↗
PubMed2004

Decreased oxidative stress in prehepatic portal hypertensive rat livers following the induction of diabetes.

1. Oxidative stress (OS) is a biological entity indicated as being responsible for several pathologies, including diabetes. Diabetes can also be associated with human cirrhosis. Portal hypertension (PH), a major syndrome in cirrhosis, produces hyperdynamic splanchnic circulation and hyperaemia. The present study was designed to investigate the occurrence of OS in prehepatic PH rat livers following the induction of diabetes. 2. Five groups of rats were used: control, sham operated, chronic diabetes (induced with a single dose of streptozotocin at 60 mg/kg, i.p.), prehepatic PH and chronic diabetic plus prehepatic PH. The occurrence of OS was determined in liver homogenates by measuring hydroperoxide-initiated chemiluminescence and the activity of anti-oxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). 3. Prehepatic PH produced a significant increase in hydroperoxide-initiated chemiluminescence in the liver compared with control and sham-operated rats, whereas the liver in chronic diabetic rats showed no difference. However, chemiluminescence values decreased almost by 50% in the chronic diabetic plus prehepatic PH group. Concomitantly, the activities of the anti-oxidant enzymes in chronic diabetes, prehepatic PH and chronic diabetic plus prehepatic PH groups were decreased (P < 0.05 vs control and sham-operated groups). 4. Livers from the chronic diabetic group did not show any evidence of the occurrence of OS, whereas the prehepatic PH group showed the occurrence of OS. The association of PH and chronic diabetes resulted in a significant decrease in the occurrence of OS, which could be explained by an anti-oxidant response to an OS.

Animals↗
PubMed2001

[Functional alterations in central nervous system of prehepatic portal hypertensive rats].

Prehepatic Portal Hypertension (PH) leads to morphologic changes in the rat Central Nervous System, including alterations of the blood brain barrier (BBB), and astrogliosis and angiogenesis in CA1 and CA4 hyppocampal fields. The present study investigates functional changes in portal hypertensive rats. Wistar Kyoto rats were used (240 g/bw) and allotted in two groups: GI (n = 8) portal hypertensive rats obtained through a regulated stenosis of the portal vein (Groszmann), and GII (n = 6), sham-operated rats. We have analyzed: BBB integrity with the Trypan Blue diffusion method (TB, Reynolds), protein concentration (PC) in Cerebrospinal Fluid (CSF) and plasma (Bradford method), electroencephalographic activity (EEG), cerebral edema expressed as brain water content (gravidimetric test), and behavior: Animex, righting reflex, pain reflex and Rotarod. TB was positive in GI in peripheral vascular areas in hippocampus, PC in CSF (ug/ml)(mean +/- SED) was GI: 40.6 +/- 6.8 and GII: 16.5 +/- 4.2 (p < 0.005), and the plasma levels were (mg/ml): GI: 108.8 +/- 7.6 and GII: 87.4 +/- 2 (NS). The EEG showed a higher power of the delta band in hypertensive rats (GI: 0.551 +/- 0.033 and GII: 0.342 +/- 0.031, p < 0.008), but water content was not different between GI and GII (water%/per/g/tissue) (GI: 79.21 +/- 0.2, GII: 78.95 +/- 0.18). These results, showing functional changes in the BBB and brain activity without behavioral alterations, suggest the development of a subclinic form of hepatic encephalopathy in our model of PH rats.

Animals↗
PubMed2000

[Does TNF-alpha contribute to liver disease physiopathology?].

The aim of the present paper is to establish the possible role of serum TNF in the pathophysiology of three experimental models of liver injury: paracetamol intoxication, cholestasis followed by paracetamol intoxication and cholestasis. We concluded that under our experimental conditions the serum TNF-alpha levels were not responsible for the inflammatory phenomena described in our previous paper as apoptosis.

Acetaminophen↗
PubMed1999

Dose-dependent increase of oxidative damage in the testes of rats subjected to acute iron overload.

This study describes the in vivo response of rat testes to acute iron overload. Male Wistar rats (250-300 g) were injected ip with iron dextran at doses of 250 (Fe250), 500 (Fe500), or 1000 mg/kg body wt (Fe1000) or with saline (C). Parameters of oxidative stress and iron toxicity were measured 20 h after injection. Total iron content was 3.5-, 5.3-, and 10.4-fold higher in the Fe250, Fe500, and Fe1000 groups, respectively, compared to controls (320 +/- 22 nmol/g tissue). Histological studies showed that: (a) iron accumulated in the sperm and other testes cells, and (b) spermatogenesis was markedly lower in the Fe1000 group. The concentration of alpha-tocopherol, ubiquinol-9, and ubiquinol-10 in the testes was inversely correlated with the extent of oxidation. Testes chemiluminescence was 45% higher in the Fe1000 group compared to controls (41 cps/cm(2)). Endogenous levels of lipid oxidation, evaluated as 2-thiobarbituric acid-reactive substances, were 46, 73, and 82% higher in the groups Fe250, Fe500, and Fe1000, respectively, than in controls (33.6 +/- 1.4 nmol/g tissue). Oxidative damage to DNA evaluated by the presence of 8-oxo-2'-deoxyguanosine (oxo(8)dG), was 26, 39, and 74% higher in the Fe250, Fe500, and Fe1000 groups, respectively, than in the C group (2.3 +/- 0.1 oxo(8)dG/10(5)dG). Protein oxidation was measured as protein thiols and carbonyl content in proteins and glutamine synthase activity. Protein thiols content and glutamine synthase activity were similar in all the groups, while the protein-associated carbonyls content was 96% higher in the Fe1000 group than in the C group (2.1 +/- 0.4 nmol/mg protein). No changes in the activities of superoxide dismutase, catalase, and glutathione peroxidase were observed. The results showed that in vivo iron overload induced oxidative stress and the impairment of spermatogenesis in rat testes that were dependent on the amount of iron supplemented and its accumulation in the tissue.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Drug glucuronidation and hepatic lipid microsomal membrane profile in cholestatic rats followed paracetamol intoxication.

The uridin-diphosphoglucuronyl-transferase (UDP-GT) is a membrane-bound enzyme responsible for glucuronidation of endogenous and exogenous compounds. This work established the UDP-GT activity and its lipid membrane microenvironment in two experimental models: acute paracetamol intoxication, and cholestasis followed by acute paracetamol intoxication. Cholestasis was performed by bile duct ligation. After 7 days animals were injected with paracetamol (BDL-APAP group). Sham-operated rats were injected at day 7 with paracetamol (APAP group). Cholestatic and sham-operated rats injected with vehicle (BDL and control groups). UDP-GT activity was measured by a kinetic method for different substrates. Microsomal membrane phospholipid composition, cholesterol content and ultrastructure were determined. BDL-APAP group showed an increment in the UDP-GT activity except for chloramphenicol, morphine and paracetamol if compared to controls and to BDL group. The same increment was observed when BDL-APAP was compared to APAP except for chloramphenicol and lorazepam. Between BDL and APAP groups similar levels of activity were detected except for paracetamol. Microsomal phospholipid profile: phosphatidylcholine showed the lowest content in the BDL group, with a significant recovery in the BDL-APAP and APAP groups. Phosphatidylserine was markedly decreased in the APAP group compared to the rest and phosphatidylinositol was decreased in all the groups if compared to control values. An increment of phosphatidylethanolamine was seen in the APAP and BDL-APAP groups if compared to BDL and control values. A significant increment of microsomal cholesterol content was seen in BDL. Under these conditions, a different lipid microenvironment is produced, resulting in an increment of the enzyme activity for a variety of substrates.

Acetaminophen↗
PubMed1999

[Benzodiazepines metabolism in various models of experimental liver diseases].

The aim of the present paper is to establish possible disturbances in benzodiazepines glucuronidation in two experimental models of liver injury: paracetamol acute intoxication and cholestasis followed by paracetamol acute intoxication. We concluded that, despite the alterations observed in liver microsomal lipid profile, glucuronidation remained similar to controls in paracetamol intoxicated rats. On the contrary, cholestatic animals followed by paracetamol intoxication showed an increment in the glucuronidation of the utilized substrated.

Acetaminophen↗
PubMed1998

Variations in rat biochemical parameters after buckshot implant.

Twenty eight albino Wistar rats were implanted with two 100 mg lead spheres: 14 received the implant in the peritoneum (P) and 14 in the thigh (T). Variations in the activity of delta-aminolevulinic dehydratase (ALAD), of urinary delta-aminolevulinic acid (ALAU), of hematoporphyrins (HP) and of lead blood levels (BPb) were then determined at 30, 60 and 90 days with respect to basal values. Parallel determinations were performed by the same schedule in 7 rats implanted with two glass beads and in 8 sham animals receiving surgical incision alone. Techniques employed for ALAD were Berlin and Schaller; for ALAU, Tomokuni and Ogata; for HP, Piomelli; and for BPb, atomic absorption spectrophotometry. As indicators of lead presence, HP and ALAU proved better, both in P and in T rats. The replacement of lead buckshot for small game hunting by other less toxic elements is recommended.

Aminolevulinic Acid↗
PubMed1998

Prostanoid production in endothelial and Kupffer liver cells from monocrotaline intoxicated rats.

UNLABELLED: A single dose of monocrotaline, a pyrrolizidine alkaloid, was injected into rats in order to produce 25 (Group I) and 45 (Group II) days later a progressive and so called delayed liver injury. The present study investigated the prostanoid production of Kupffer cells and endothelial cells separated from Monocrotaline and saline (Group III) injected rat livers. Kupffer cells: formation of 6 keto Prostaglandin F1 alpha, the major prostacycline metabolite, gradually decreased in Groups I vs II (P < 0.01) and in both Groups I and II vs Controls (P < 0.01). In addition Prostaglandin F2 alpha showed a significant increase in Groups I and II when compared to Group III, (P < 0.001), and Thromboxane B2 was present in both Groups of Monocrotaline treated animals, while it was not detectable in the control Group III. Endothelial cells: 6 keto Prostaglandin F1 alpha decreased in Groups 1 vs II. This differences was significant when compared, and compared to controls (Group III, P < 0.001). Prostaglandin E2 was detected only in Groups I and II. Prostaglandin F2 alpha and Thromboxane B2 could not be detected in any Group. Ultramicroscopy showed morphological cell damage in nonparenchymal cells in Monocrotaline intoxication in Group II, rats sacrificed 45 days after the injection, while it shows normal features in those treated animals sacrificed 25 days after the injection, as well as in control group. CONCLUSION: A single Monocrotaline injection produces, 25 and 45 days later, severe and progressive alterations in the prostanoid production in Kupffer and Endothelial cells, while ultramicroscopic alterations was only observed 45 days after the injection of Monocrotaline. A decreased production of vasodilators and the presence of vasoconstrictor prostanoids that can participate in the production of the circulatory derangements enhancing liver injury and portal hypertension were also observed.

Animals↗
PubMed1995

Cholestasis as a liver protective factor in paracetamol acute overdose.

1. The effect of paracetamol overdoses on its disposition was investigated in cholestatic rats. 2. Paracetamol plasma concentration and hepatic accumulation decrease about 70-80% in cholestatic rats. 3. Cholestatic rats intoxicated with paracetamol showed less hepatic damage as concluded from biochemical and histological findings. These data are correlated with liver and plasmatic paracetamol. 4. These results indicate a decrease in paracetamol toxicity related to stagnant bile.

Acetaminophen↗
PubMed1995

[Development of biochemical and histopathological parameters in paracetamol overdose in experimental cholestasis].

The aim of the present paper is to determine the effect of Paracetamol (P) acute intoxication in cholestatic rats. Four groups of animals were considered: controls, controls intoxicated with P, rats intoxicated with P and cholestatic rats. Hepatic biochemical tests and liver histology were performed in every group. It is concluded that cholestatic rats intoxicated with P showed less Liver damage than in control groups.

Acetaminophen↗
PubMed1988

Effect of chemical modification with p-bromophenacyl bromide on the enzymatic and lethal properties of phospholipase A2 from Bothrops alternatus (Víbora de la Cruz) venom.

The effects on lethal potency and enzymatic activity were determined following alkylation, with p-bromophenacyl bromide, of the acidic toxic phospholipase A2 from Bothrops alternatus. The modified B. alternatus enzyme, which lost its enzymatic activity, retained considerable toxicity. Histopathologic studies on mice have demonstrated features similar to those of the native enzyme. However, the distribution of the damage was different and the survival time was longer. It is concluded that the enzyme activity is not important for the lethal action of the enzyme although it influences the distribution of the damage and survival time.

Acetophenones↗
PubMed1988

Effects of unilateral ureteric occlusion on renal necrosis occurring in rats fed a methyl-deficient diet.

Wistar male rats were fed from weaning a methyl-deficient diet (groups I and II) or a standard commercial diet (groups III and IV). At the day 3 the left ureter was tied and divided in animals of groups I and III, while those in groups II and IV were sham operated. Rats of all groups were killed on days 8 and 10 to evaluate the incidence and extent of tubular necrosis (day 8) and tubular and cortical necrosis (day 10). The results of this study show that unilateral ureteric obstruction diminishes the incidence, severity and extent of necrosis in the same kidney.

Acute Kidney Injury↗
PubMed1986

Contribution of phospholipase A2 to the lethal potency of Bothrops alternatus (víbora de la cruz) venom.

Purified phospholipase A2 from Bothrops alternatus venom is one single protein species with a molecular weight of 15,000 and isoelectric point 5.08. When injected i.p. or i.v. at a dose of 0.7 microgram/g body weight it is lethal to mice, eliciting a typical syndrome of dyspnea, tachycardia, arrhythmia and irreversible shock. Post mortem and histopathologic studies have demonstrated that the lungs (massive pulmonary hemorrhage), heart (foci of myocardial and endocardial necrosis with interfibrillar hemorrhage), liver (congestion, hepatocytic microvacuolization with zones of massive necrosis) and kidneys (foci of tubular and glomerular necrosis) were severely injured. Except for the less extensive hemorrhages and the significantly longer survival time, the observed lesions are similar to those observed after the injection of lethal doses of whole venom. The lethal potency of the purified enzyme (LD50 i.p. 0.14 microgram/g body weight) is 46-fold greater than that of the whole venom (LD50 i.p. 6.4 micrograms/g body weight). The contribution of phospholipase A2 to the overall lethal effect of B. alternatus venom is suggested by the decreased lethal potency of a venom sample in which a significant amount of phospholipase A2 has been removed and the full restoration of the lethal potency upon supplementation of the depleted sample with purified enzyme. It is concluded that phospholipase A2 is a major component responsible for lethality of the whole B. alternatus venom, while the contribution of other venom components appears to be significant mainly in reducing the time of survival.

Animals↗