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Biomedical subjects

C Marín

Publications and source records attributed to C Marín.

At least 19 recordsLinked to original sources
PubMed2002

The SstI polymorphism of the apo C-III gene is associated with insulin sensitivity in young men.

AIMS/HYPOTHESIS: Insulin resistance is considered to be a risk factor for diabetes and coronary heart disease and is determined by the interaction between genetic and environmental factors. The SstI polymorphism in the apolipoprotein C-III gene has been related to the presence of different features of the insulin resistance syndrome. We investigate if this mutation influences the peripheral effect of insulin in healthy young subjects (30 men and 29 women) eating a westernised diet. METHODS: We investigated peripheral insulin sensitivity with the insulin suppression test after a 28-day westernised high-saturated fat diet (38% total fat and 18% saturated fat with 115 mg of cholesterol per 1000 Ju). RESULTS: Steady state plasma glucose values were lower in S1-S1 compared with S1-S2 men (p=0.018 by ANOVA), but not in women (p=0.723). CONCLUSION/INTERPRETATION: There was no difference between carriers and non-carriers of the S2 allele in relation to incidence and sensitivity; although on subgroup analysis there was an effect in men but not in women.

Adult↗
PubMed2002

Cerivastatin improves insulin sensitivity and insulin secretion in early-state obese type 2 diabetes.

In a double-blind, placebo-controlled, randomized crossover study, 15 stable mild hyperglycemic patients without treatment and with features of metabolic syndrome were treated with cerivastatin (0.4 mg/day) or placebo for 3 months. The insulin sensitivity index during the euglycemic-hyperinsulinemic clamp (EHC; 5.4 mmol/l; 80 mU x m(-2) x min(-1)) was increased by cerivastatin treatment (66.39 +/- 3.9 nmol x lean body mass [LBM](-1) x min(-1) x pmol(-1) x l(-1)) as compared with placebo (58.37 +/- 3.69 nmol x LBM(-1) x min(-1) x pmol(-1) x l(- 1); P < 0.01) by 13.7%. Glucose oxidation during EHC was significantly higher with statin treatment (16.1 +/- 1.37 micromol x LBM(-1) x min(-1)) as compared with placebo (14.58 +/- 1.48 micromol x LBM(-1) x min(-1); P < 0.05). During hyperinsulinemia (approximately 800 pmol/l) in EHC steady-state, lipid oxidation was significantly decreased and respiratory quotient was significantly increased with statin treatment (0.33 +/- 0.05 mg x LBM(-1) x min(- 1), 0.94 +/- 0.01) as compared with placebo (0.48 +/- 0.06 mg x LBM(-1) x min(-1), 0.91 +/- 0.01; P < 0.01 and P < 0.05, respectively). During statin treatment, the first-phase insulin response increased from 2.07 +/- 0.28 to 2.82 +/- 0.38 pmol x l(-1) x pmol(-1) (P < 0.05). The second phase of insulin responses examined by C-peptide and insulin levels averaged during the hyperglycemic clamp (20 mmol/l) was unchanged. In conclusion, this study demonstrates that 0.4 mg cerivastatin therapy improves first-phase insulin secretion and increases insulin-mediated glucose uptake and respiratory quotient in the early state of obese type 2 diabetes.

Blood Glucose↗
PubMed2001

Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men.

BACKGROUND: The regulatory function of the endothelium is altered in hypercholesterolemia, and the subsequent endothelial dysfunction plays a central role in the development of atherosclerosis. OBJECTIVE: To determine whether endothelial function in hypercholesterolemic patients is affected by replacing a saturated fat-enriched diet with a low-fat, low-saturated fat diet (the U.S. National Cholesterol Education Program stage 1 [NCEP-1] diet) or a diet rich in monounsaturated fat (such as that common in Mediterranean countries). DESIGN: Intervention dietary study with a baseline phase and two randomized crossover dietary periods. SETTING: Hospital Universitario Reina Sofía, Córdoba, Spain. PATIENTS: 22 hypercholesterolemic men. INTERVENTION: Patients followed a diet high in saturated fat, then were assigned in a crossover design to the NCEP-1 diet or a Mediterranean diet. Each dietary period lasted 28 days. MEASUREMENTS: Plasma P-selectin levels, lipid concentrations, and endothelial function. RESULTS: Compared with the saturated fat diet, flow-mediated dilatation increased during the Mediterranean diet but not during the NCEP-1 diet. In addition, levels of plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and P-selectin decreased during the NCEP-1 and Mediterranean diets. CONCLUSION: In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial function.

Adolescent↗
PubMed2001

A Mediterranean and a high-carbohydrate diet improve glucose metabolism in healthy young persons.

AIMS/HYPOTHESIS: Insulin resistance usually precedes the diagnosis of Type II (non-insulin-dependent) diabetes mellitus. However, in most patients, the clinical expression of the disease could be prevented by dietary and lifestyle changes. We investigated the effects of a diet enriched in monounsaturated fatty acids (Mediterranean diet) and a low fat, high-carbohydrate diet on in vivo and in vitro glucose metabolism in 59 young subjects (30 men and 29 women). METHODS: We carried out an intervention dietary study with a saturated fat phase and two randomized-crossover dietary periods: a high-carbohydrate diet and a Mediterranean diet for 28 days each. We analysed the plasma lipoproteins fractions, free fatty acids, insulin sensitivity and glucose uptake in isolated monocytes at the end of the three dietary periods. RESULTS: In comparison to the saturated fat diet, the CHO and Mediterranean diets induced a decrease of LDL-cholesterol (p < 0.001) and HDL-cholesterol (p < 0.001). Steady-state plasma glucose decreased (p = 0.023) and basal and insulin-stimulated 2-deoxiglucose uptake in peripheral monocytes increased in both diets (CHO and Mediterranean), (p = 0.007) indicating an improvement in insulin sensitivity. Fasting free fatty acids plasma values were correlated positively with steady state plasma glucose (r = 0.45; p < 0.0001). In addition, there was an inverse correlation between the mean glucose of the steady state plasma glucose period and logarithmic values of basal (r = -0.34; p = 0.003) and insulin stimulated glucose uptake in monocytes (r = -0.32; p = 0.006). CONCLUSION/INTERPRETATION: Isocaloric substitution of carbohydrates and monounsaturated fatty acids for saturated fatty acids improved insulin sensitivity in vivo and in vitro, with an increase in glucose disposal. Both diets are an adequate alternatives for improving glucose metabolism in healthy young men and women.

Adult↗
PubMed2001

Tubular stress test detects subclinical reduction in renal functioning mass.

BACKGROUND: To develop a test that would disclose subclinical impairment in renal function, we studied the increment in tubular secretion of creatinine (TS(Cr)) induced by intravenous creatinine administration. METHODS: Studies were done in 14 normal individuals, 7 kidney donors (KDs), and 11 transplant recipients (Tx), all of whom had normal creatinine levels (P(Cr) <133 micromol/L). Creatinine infusion studies determined that maximal stimulation of TS(Cr) resulted from P(Cr) levels of 500 to 700 micromol/L. Therefore, in the tubular stress test, clearances, urinary excretion of creatinine (U(Cr)V) and TS(Cr) were determined before and after (15 to 105 min) a single bolus injection of 88.4 mmol/kg body wt, which resulted in the target P(Cr) levels. RESULTS: Baseline determinations of P(Cr), U(Cr)V, and TS(Cr) were not significantly different in the study groups. Stimulated U(Cr)V (nmol/kg/min) was higher in normals (426 +/- 82) than in KDs (338 +/- 72, P < 0.05) and Tx patients (311 +/- 66, P < 0.01). Similarly, TS(Cr) (nmol/kg/min) was higher (P < 0.001) in normals (180 +/- 60) than in KDs (155 +/- 54) and Tx patients (86 +/- 35). Furthermore, the transplanted kidney responded worse than the solitary normal kidney (P < 0.05), despite having similar levels of glomerular filtration rate (GFR). The tubular stress test increased TS(Cr) 11.3 +/- 6.2 times in normals, 4.3 +/- 1.2 times in KDs (P < 0.01), and 2.5 times in Tx (P < 0.001). CONCLUSIONS: Impaired tubular secretory response to a creatinine load is a more sensitive index of reduced functioning renal mass than levels of P(Cr) and GFR. The tubular stress test may be useful in following the natural history of kidney disease and the results of therapeutic interventions.

Adult↗
PubMed2001

Multiplex-polymerase chain reaction assay for the detection of prognostically significant translocations in acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: The presence of specific chromosomal translocations in acute lymphoblastic leukemias (ALL) plays an important role in determining the prognosis of the patients. Our aim is to develop a highly sensitive and specific method to screen simultaneously for the four most frequent translocations in ALL: t(9;22), t(1;19), t(4;11), t(12;21). DESIGN AND METHODS: Our approach uses a multiplex-polymerase chain reaction (PCR) method, which involves two rounds of PCR using fluorescence-labeled nested primers. The chimeric transcripts resulting from these translocations can be identified by agarose gel electrophoresis or by fluorescence analysis. To validate this method we carried out the analysis in 42 pediatric ALL samples previously studied by cytogenetic and fluorescent in situ hybridization (FISH) techniques. RESULTS: In all samples with a known translocation detected by cytogenetic or FISH techniques, the same translocation was identified by the multiplex-PCR assay. Moreover, with this method we detected rearrangements in five patients in clinical remission and in two patients at diagnosis for whom karyotypes were normal and rearrangements had not been detected. The application of this multiplex-PCR assay was also useful in cases without cytogenetic results. INTERPRETATION AND CONCLUSIONS: These results show that the multiplex-PCR method allows reliable, sensitive and rapid detection of the prognostically significant translocations in ALL. We believe that this assay combined with cytogenetic analysis should be the strategy of choice for the initial diagnostic phase of acute lymphoblastic leukemia, and that it could be used not only at diagnosis but also to follow-up these alterations in remission samples without previous controls.

Child↗
PubMed2001

Interaction between smoking and the Sstl polymorphism of the apo C-III gene determines plasma lipid response to diet.

BACKGROUND: It has recently been demonstrated that the lipid profile of smokers improves if they follow a Mediterranean diet. AIM: To establish whether the Sstl polymorphism of the apo C-III gene interacts with smoking and determines the lipid response to diet in healthy subjects. METHODS AND RESULTS: Fifty-nine volunteers (18 smokers: 8 with the S1S1 genotype, and 10 with the S2 allele; 41 non-smokers: 29 with the S1S1 genotype and 12 with the S1S2 genotype) consecutively followed three different diets: a diet enriched in saturated fatty acids (SFA) (38% fat, 20% SFA) followed by a randomised, cross-over period during which they ate a diet enriched in carbohydrates (NCEP-1) (30% fat, 10% SFA, 55% carbohydrates) and a diet enriched in monounsaturated fatty acids (MUFA) (8% fat, 22% MUFA). Cholesterol, triacylglycerol, LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels were measured at the end of each dietary period. The smokers carrying the S1S1 genotype were not influenced by any of the diets, but the atherogenic ratio decreased in the carriers of the S2 allele when they changed from the diet rich in SFA to a diet rich in olive oil or carbohydrates (p < 0.039). No significant difference was observed when the non-smoking carriers of the S2 allele changed from one diet to another, but there was a decrease in the LDL-C/HDL-C ratio when the subjects with the S1S1 genotype changed from the saturated diet to either of the other diets (p < 0.001). CONCLUSIONS: Smoking interacts with the apo CM polymorphism and determines the level of lipid response to dietary changes.

Adult↗
PubMed2000

[Mediterranean diet improves low density lipoprotein susceptibility to oxidative modifications].

UNLABELLED: Most experts, specially from Anglo-Saxon countries, recommend a low fat diet in order to prevent cardiovascular diseases. However, mortality rate by ischemic cardiopathy is low in Mediterranean countries, probably because of the consumption of a Mediterranean diet, with a high level of monounsaturated fats provided by the olive oil. We have conducted this study in order to investigate the possible influence of this kind of diet on the oxidation of LDL in vitro, the key element for the development of atherosclerosis. PATIENTS AND METHODS: 41 healthy male subjects were submitted to three consecutive 4-week diets. The first was a saturated fat-rich diet (SAT diet, 38% fat, 20% saturated). This was followed by a low fat diet (NCEP-I, 28% fat, 10% saturated) and after that a Mediterranean diet (38% fat, 22% monounsaturated fat). Plasma levels of total cholesterol, LDL-c, HDL-c, triglycerides, apolipoproteins A-I and B, -tocopherol, and the in vitro susceptibility to oxidation of LDL particles. Both hypolipidemic diets produced a significant decrease in total cholesterol, LDL-c, and apo-B plasma levels. However, it was only the NCEP-I diet that revealed a decrease in the HDL-c. The shift from a saturated fat-rich diet, or a diet rich in carbohydrates, to a Mediterranean diet increased the resistance of LDL particles to oxidation increasing the lag time period (p < 0.038), and decreasing (p < 0.001) the progression rate of the curve of oxidation of LDL. Our results point out two positive consequences of the consumption of a Mediterranean diet by healthy young males, compared with the low fat diet recommended by most Anglo-Saxon experts. On the one hand, the Mediterranean diet increases HDL-c plasma levels, and on the other hand, it decreases the susceptibility of LDL to oxidation. This is why the Mediterranean diet must be recommended in order to prevent cardiovascular diseases.

Adult↗
PubMed2000

Brain-derived neurotrophic factor in Huntington disease.

Trophic factors, administered systemically or delivered via genetically-modified cells grafted into target regions, have been proposed as putative therapeutic agents in human neurodegenerative disorders. In parallel to the study of the beneficial effects in experimental models of particular diseases, a crucial aspect of the study of trophic factors is the gathering of information about the actual trophic factor expression in human diseased states. Brain-derived neurotrophic factor (BDNF) promotes survival and growth of various nerve cell populations during normal development and following various insults in the developing and adult brain. In particular, BDNF prevents cell death of certain striatal populations in excitotoxic models of Huntington disease (HD) following intrastriatal injection of quinolinic acid to the adult rodent brain. The present study examines BDNF expression, by gel electrophoresis and Western blotting, and immunohistochemistry, in the brains of patients who had suffered from HD. Reduced BDNF expression, ranging from 53 to 82%, has been found in the caudate and putamen in HD when compared with age-matched controls. No modifications in BDNF expression levels have been seen in the parietal cortex, temporal cortex and hippocampus. Furthermore, immunohistochemistry has shown reduced BDNF immunoreactivity in caudate neurons, but not in cortical neurons in HD when compared with controls. These data demonstrate selective BDNF decay in regions that are vulnerable to HD, and suggest, in combination with results in experimental models, that a BDNF surplus may have beneficial effects in the treatment of HD.

Aged↗
PubMed2000

Brain-derived neurotrophic factor in patients with frontotemporal dementia.

Brain-derived neurotrophic factor (BDNF) promotes survival and growth of various nerve cell populations during normal development and following different insults in the developing and adult brain. BDNF expression is reduced in Alzheimer disease, but little is known about BDNF expression in other types of dementia. Frontotemporal dementia (FTD) is a common cause of mental impairment in old age, which is characterized by neuron loss in the upper cortical layers mainly of the frontal and temporal cortex. BDNF protein expression has been examined by Western blotting and immunohistochemistry in the cerebral cortex of individuals affected by FTD. Examination of pathological samples (n = 8, mean age: 74.7 years; four men, four women) was conducted in parallel with corresponding samples from age-matched controls (n = 8; mean age: 72.6 years; three men, five women). Post-mortem delay was between 2 and 6 h. Preserved BDNF expression, as revealed by Western blotting, has been observed in the frontal and temporal cortices of patients with FTD. Furthermore, immunohistochemistry has disclosed maintained BDNF immunoreactivity in surviving neurons of the upper cellular layers, as well as in neurons of the inner cellular layers in FTD. These results show that FTD is not associated with a decay of BDNF in cortical neurons, and therefore, that BDNF is differentially regulated in diseases causing dementia.

Aged↗
PubMed2000

The effect of apolipoprotein B xbaI polymorphism on plasma lipid response to dietary fat.

BACKGROUND AND AIMS: Lipid response to dietary fat and cholesterol is, to a large extent, genetically controlled. Apolipoprotein B (apo B) plays a dominant role in cholesterol homeostasis. Several polymorphic sites within or adjacent to the gene locus for apo B have been detected. The X+ allele of the XbaI restriction fragment polymorphism of the apo B gene has been found to be associated with higher serum cholesterol and/or triglyceride levels. In order to study the influence of this mutation on the plasma lipid response in diets of varying fat content, 72 healthy male subjects were studied, 21 X- X- (X-) and 51 X+ (X+ X- or X+ X+). METHODS AND RESULTS: These subjects followed three consecutive 28-day diet periods: one rich in saturated fats (SAT diet; 38% fat, 20% saturated); a National Cholesterol Education Program type I diet (NCEP-I diet) (28% fats, < 10% saturated); and a third monounsaturated (MUFA diet) (38% fats, 22% monounsaturated). The different genotypes can be observed to have significant effects on total and LDL cholesterol concentrations (P < 0.017). X+ individuals had higher levels of total and LDL cholesterol after the consumption of a SAT diet (P < 0.012; P < 0.006, respectively), NCEP diet (P < 0.060; P < 0.054, respectively) and MUFA diet (P < 0.022; P < 0.042, respectively) in comparison with X- individuals. A significant interaction between genotypes and dietary effects was observed for diet-induced changes in plasma triglycerides (P < 0.032). Significant decreases in the absolute values of triglyceride concentrations (-0.18 mmol L(-1), P < 0.024) were noted in the X- subjects after the high intake of a MUFA diet, while no significant differences were observed in the X+ individuals (0.006 mmol L(-1), P < 0.858). CONCLUSIONS: Our results suggest that the total triglyceride response to diet is influenced by the apo B XbaI polymorphism.

Adult↗
PubMed2000

Low-fat and high-monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men.

BACKGROUND: Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. OBJECTIVE: The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. DESIGN: : We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. RESULTS: Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. CONCLUSIONS: The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.

Adult↗
PubMed1999

Circulating levels of endothelial function are modulated by dietary monounsaturated fat.

BACKGROUND: For the most part, the benefits of monounsaturated-rich diets (MUFA-diet) have been related to their action on plasma lipid levels. However other non-lipidic effects could also be involved in their protective effects. One of these involves the decrease in plasma levels of plasminogen activator inhibitor type 1 (PAI-1), the main inhibitor of fibrinolysis. Given that the PAI-1 is of endothelial origin, one hypothesis is that the MUFA-diet could protect against CHD by modulating some endothelial components. METHODS AND RESULTS: Healthy male subjects (n = 25) received three different consecutive diets, each lasting 28 days: a low fat NCEP-I-diet, with 28% calories as fat, 10% saturated fat (SAT), 12% monounsaturated (MUFA) and 6% polyunsaturated (PUFA); a MUFA-diet, with 38% calories as fat, 10% SAT, 22% MUFA and 6% PUFA; and a SAT rich-diet (SAT-diet), with 38% calories as fat, 20% SAT, 12% MUFA and 6% PUFA. After each dietary period, the plasma lipid profile was determined, including total cholesterol, HDL cholesterol, LDL cholesterol, total triglyceride, apo A1, apo B plasma levels and conjugated diene formation, after incubation of LDL particles with Cu 5 microM/l. Endothelial products measured in plasma were von Willebrand factor (vWF), E-selectin, Thrombomodulin and Tissue Factor Pathway Inhibitor (TFPI) levels. We observed a decrease in vWF, PAI-1 and TFPI plasma levels and an increase in lag time of conjugated diene formation after the MUFA-diet. There was a positive correlation between the decreases in TFPI and vWF and the changes in total cholesterol, LDL-C, apo B plasma levels. The decrease in TFPI was negatively correlated with the increase in lag time of conjugated diene formation. PAI-1 plasma levels were positively correlated with total cholesterol, LDL-C and triglycerides and negatively correlated with HDL-C. CONCLUSIONS: Consumption of a Mediterranean-type MUFA-diet produces a decrease in plasma levels of vWF, TFPI and PAI-1 plasma levels in young healthy males. Given that these substances are of endothelial origin, one could suggest that the MUFA of the diet has a beneficial effect on endothelial function resulting in protective changes against thrombogenesis.

Adult↗
PubMed1999

BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies.

Brain-derived neurotrophic factor (BDNF), and full-length and truncated tyrosin kinase B receptor (TrkB) protein expression were examined by Western blotting and immunohistochemistry in the frontal cortex and hippocampus of individuals affected by long-lasting severe Alzheimer disease (AD) and age-matched controls. Since preliminary processing studies in the brains of rats have shown loss of immunoreactivity depending on the postmortem delay in tissue processing and on the type, duration, and temperature of the fixative solution, only human samples obtained up to 6 hours (h) after death for biochemical and morphological studies and fixed by immersion in 4% paraformaldehyde for 24 h for morphological studies were included in the present series. Decreased BDNF and full-length TrkB expression accompanied by increased truncated TrkB expression, as revealed by Western blotting, was observed in the frontal cortex of patients with AD. Immunohistochemistry disclosed reduced BDNF and full-length TrkB immunoreactivity in neurons. BDNF decrease was equally observed in tangle-bearing and non-tangle-bearing neurons, as revealed with double-labeling immunohistochemistry to BDNF and phosphorylated tau or phosphorylated neurofilament epitopes. Full-length TrkB immunoreactivity was largely decreased in tangle-bearing neurons, whereas only moderate decreases occurred in neurons with granulovacuolar degeneration. Strong BDNF immunoreactivity was observed in dystrophic neurites surrounding senile plaques, whereas strong TrkB expression occurred in reactive glial cells, including those surrounding senile plaques. Finally, truncated TrkB immunoreactivity was observed in individual neurons and in reactive glial cells in the cerebral cortex and white matter in AD. These results show decay in the expression of BDNF and TrkB in AD neurons, accompanied by altered BDNF, and full-length and truncated TrkB expression in dystrophic neurites and reactive glial cells, respectively, in this disease. The present results demonstrate selective decline of the BDNF/TrkB neurotrophic signaling pathway in the frontal cortex and hippocampus in AD and provide supplemental data that may be relevant in discussing the suitability of the use of BDNF as a therapeutic agent in patients with AD.

Aged↗
PubMed1998

Biochemical and molecular effects of chronic haloperidol administration on brain and muscle mitochondria of rats.

The objectives of the current study were to evaluate (1) the respiratory rates and enzyme activities of brain and muscle mitochondria from rats chronically treated with haloperidol, (2) the protective role of dopamine (DA) D-1 (SKF38393) and D-2 (quinpirole) receptor agonists, and (3) the effect of haloperidol on the mitochondrial DNA (mtDNA) and protein synthesis. Thirty male Sprague-Dawley rats were subdivided into the following five groups: controls, haloperidol, haloperidol plus SKF38393, haloperidol plus quinpirole, and haloperidol plus SKF38393 and quinpirole. We compared the respiratory rates and enzymatic activities of brain and muscle mitochondria from controls with other groups. We finally analyzed the mitochondrial protein synthesis and mtDNA alterations (deletions, point mutations, and depletion) in two rats from each group. In brain but not in muscle from haloperidol-treated rats, we found a decrease of oxygen consumption rates using glutamate plus malate (-68 +/- 35%, P < 0.05) and succinate (-78 +/- 20%, P < 0.05) as substrates as well as low complex I, II, and V activities (-35 +/- 15%, P < 0.05; -54 +/- 13%, P < 0.05; and -60 +/- 33%, P < 0.01; respectively). The administration of SKF38393 alone or together with quinpirole prevented most of haloperidol-induced effects, whereas the protective effects of quinpirole alone were lower. Brain mitochondrial protein synthesis was decreased in haloperidol-treated rats and was not prevented by SKF38393, quinpirole, or both. We did not find mtDNA abnormalities in brain or muscle mitochondria from haloperidol-treated rats. Chronic administration of haloperidol in rats is associated with a nonspecific deleterious effect in the activity of electron transport chain of brain, and this effect is only partially prevented by DA D-1 agonists. These results suggest that other mechanisms different from DA receptors pathway can contribute to the expression of behavioral supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗