Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver.

Although carbon tetrachloride (CCl(4))-induced acute and chronic hepatotoxicity have been extensively studied, little is known about the very early in vivo effects of this organic solvent on oxidative stress and mitochondrial function. In this study, mice were treated with CCl(4) (1.5 ml/kg ie 2.38 g/kg) and parameters related to liver damage, lipid peroxidation, stress/defense and mitochondria were studied 3 h later. Some CCl(4)-intoxicated mice were also pretreated with the cytochrome P450 2E1 inhibitor diethyldithiocarbamate or the antioxidants Trolox C and dehydroepiandrosterone. CCl(4) induced a moderate elevation of aminotransferases, swelling of centrilobular hepatocytes, lipid peroxidation, reduction of cytochrome P4502E1 mRNA levels and a massive increase in mRNA expression of heme oxygenase-1 and heat shock protein 70. Moreover, CCl(4) intoxication induced a severe decrease of mitochondrial respiratory chain complex IV activity, mitochondrial DNA depletion and damage as well as ultrastructural alterations. Whereas DDTC totally or partially prevented all these hepatic toxic events, both antioxidants protected only against liver lipid peroxidation and mitochondrial damage. Taken together, our results suggest that lipid peroxidation is primarily implicated in CCl(4)-induced early mitochondrial injury. However, lipid peroxidation-independent mechanisms seem to be involved in CCl(4)-induced early hepatocyte swelling and changes in expression of stress/defense-related genes. Antioxidant therapy may not be an efficient strategy to block early liver damage after CCl(4) intoxication.

Mitochondrial abnormalities in patients with HIV-HCV co-infection as compared to patients with HCV mono-infection.

INTRODUCTION: Mitochondrial dysfunction is a classic complication of HIV infection and its treatment and has also been reported in hepatitis C virus (HCV)-infected patients. Little is known about interactions between both viruses on mitochondrial metabolism. METHODS: We performed a cross-sectional study of HCV-infected patients who underwent liver biopsy as part of their routine care. Mitochondrial function was assessed by (a) liver morphological (histology) and functional (spectro-photometry) studies, and (b) serum lactate kinetics, oxygen uptake, and anaerobic threshold measurement during standardized incremental exercise. Three predefined groups of patients were compared. RESULTS: Thirty-eight HCV-infected patients were included: 13 not HIV infected (group 1), 7 with HIV co-infection and low nucleoside reverse transcriptase inhibitor (NRTI) exposure (none over the last 2 years; group 2), and 18 with HIV co-infection and high NRTI exposure (group 3). On liver biopsies, respiratory chain complex IV activity was impaired, at 5 (2-7) nmol/min/mg substrates in group 1, 5 (3-8) in group 2, and 8 (2-13) in group 3 (normal values, 20-56). Maximal power output was diminished and anaerobic threshold occurred earlier in HIV-infected patients, regardless of NRTI exposure. CONCLUSION: HCV has deleterious effects on liver mitochondrial metabolism, notably on respiratory chain complex IV. No significant interaction with HIV was observed.

Evaluation of an untargeted chemometric approach for the source inference of ignitable liquids in forensic science.

Recent research efforts in the domain of fire debris analysis have been mainly oriented towards the development of innovative analytical procedures and chemometric approaches for the detection and classification of ignitable liquids in fire specimens according to the ASTM E1618. However, less attention has been brought to the question of the source inference of ignitable liquids. Infer the identity of source of ignitable liquids recovered from arson sites is still a challenging and ongoing research area. In this study, the objective is to link neat gasoline samples sharing a common source through the use of an untargeted chemometric approach applied to data acquired by automated thermodesorption (ATD)-GC-MS following passive headspace extraction onto Tenax TA tubes. To that end, 190 unique gasoline samples from 19 gas stations collected over a year were used. A general and automated chemometric methodology for data treatment involving the following main steps is proposed: feature detection, normalization by exhaustive calculation of ratios between areas of pairs of features and selection of most discriminant ratios. The ratio selection procedure used here is based on the calculation of similarity measurements between pairs of samples sharing a common source or not. The algorithm maximizes the separation of the distributions of similarity measurements for related and unrelated samples by selecting a subset of ratios maximizing the area under the Receiver Operating Characteristics curve. The approach presented here was successfully applied to neat gasoline samples in order to assess if two gasoline samples share a common source or not.

Exploratory study on the possibility to link gasoline samples sharing a common source after alteration by evaporation or combustion.

The source inference of ignitable liquids in forensic science is still a challenging and ongoing research area. In real case applications, specimens of different natures, which may have been exposed to fire or not, may have to be compared. These comparisons are difficult since specimens may have been altered by evaporation, combustion or both. Plus, the extent of the alteration is often difficult to evaluate. Most studies concerning source inference of ignitable liquids worked on neat samples or samples altered by evaporation. However, there is a lack of studies comparing the influence of evaporation and combustion within a source inference framework. In this study, the same collection of gasoline samples was altered by both evaporation under a nitrogen stream and combustion of the gasoline adsorbed on a matrix. The possibility to link gasoline samples sharing a common source was then explored using an adaptive untargeted chemometrics workflow from feature detection to feature selection. This data treatment approach was successfully applied to the data and it was shown that the possibility to link samples with a common source was not compromised despite evaporation or combustion for degrees of alteration from 0% to 99%.

Mitochondrial abnormalities in HIV-infected lipoatrophic patients treated with antiretroviral agents.

BACKGROUND: Lipodystrophy is now widely described in HIV infected patients under antiretroviral regimen with important psychological impact. But physiopathology of loss of fat mass is still debated and the role of mitochondrial impairment is not clearly defined. OBJECTIVE: To correlate clinical lipoatrophy (LA) in HIV patients with long-term treatment by nucleoside reverse transcriptase inhibitors (NRTIs) and muscular impairment related to mitochondrial dysfunction. METHODS: Ten consecutive patients with clinical LA and 10 nonlipodystrophic (NLD) individuals on antiretroviral therapy were included. Patients underwent the following investigations: dual-energy x-ray absorptiometry (DEXA) scanning and lactate kinetics during standardized exercise. The mitochondrial respiratory complex activity (III and IV) and histoenzymatic abnormalities (classified as none, mild, or severe) were evaluated on muscle tissue obtained by biopsy in deltoid muscle. RESULTS: Mean NRTI exposure was longer in the LA group than in the NLD group (81 +/- 30 months vs. 59 +/- 15 months), but mean protease inhibitor exposure was identical in both groups. Mean fat mass distribution for leg in the LA and NLD groups was 860 +/- 381 g versus 1895 +/- 999 g, respectively. The lactic acidosis threshold during exercise was reached in the LA group at lower workloads (mean: 45 +/- 17 W in the LA group vs. 68 +/- 11 W in the NLD group), and maximum power output exercise was restricted in LA patients (mean: 115 +/- 30 W vs. 153 +/- 28 W). Total complex activities in muscular tissue were lower in LA patients: the median (range) for complex III was 67 (1-128) versus 112 (28-143), and the median (range) for complex IV was 28 (1-70) versus 42 (1-75). Six patients had severe histoenzymatic abnormalities in the LA group versus none in the NLD group. CONCLUSION: Clinical LA, confirmed by DEXA, in long-term NRTI-treated patients was associated with muscular mitochondrial dysfunction as shown by rapid lactic acidemia increase, impairment of respiratory chain activity for complexes III and IV, and mitochondrial histoenzymatic abnormalities.