RESUMO
Dilated cardiomyopathy (DCM) is an idiopathic condition that results from impaired ventricular systolic function. Thyroid diseases have been known to cause myriad changes in the structure and function of the heart. Diastolic dysfunction is a common abnormality reported in hypothyroidism. However, hypothyroidism-induced DCM and systolic dysfunction is an uncommon phenomenon, especially as the initial presenting manifestation of hypothyroidism. The current article describes the case of a young female who presented with symptoms of heart failure and was diagnosed as having DCM as echocardiography revealed left ventricular global hypokinesia and severely depressed systolic function. Thyroid profile revealed a grossly elevated thyroid-stimulating hormone (TSH) value of 313 µIU/ml; free thyroxine (fT4) was 0.220 ng/dl. The present case presented with DCM as the initial presentation of hypothyroidism and improved significantly after five months of levothyroxine replacement therapy.
Assuntos
Cardiomiopatia Dilatada/etiologia , Hipotireoidismo/complicações , Adulto , Feminino , HumanosRESUMO
AIMS: The population of the Himalayan region is known to consume a variety of fermented and nonfermented foods and as a result they have been benefited in terms of overall health, because of the associated beneficial microbes. Therefore, the focus of the present study was to identify new strains of lactic acid bacteria (LAB) from dairy products such as milk (cow, goat, buffalo) and fermented products (curd and buttermilk) with properties suitable for use as probiotic cultures. METHODS AND RESULTS: A total of 75 isolates tentatively identified as LAB from 100 samples were initially screened for production of ß-haemolysin as indicators of virulence which resulted in 38 isolates with no haemolytic activity. Further subtractive screening based on resistance to gastrointestinal tract barriers (acid and bile salts) resulted in the selection of the eight most promising strains. All these eight strains were resistant to pH 2·0, 1% bile concentration and pancreatin (1 mg l-1 ). Among the eight isolates, three isolates were identified as Brevibacillus thermoruber and the others as Brevibacillus aydinogluensis, Lactobacillus gastricus, L. paracasei, Enterococcus sp. Weisella confusa based on 16S rDNA region. Among these isolates, L. paracasei CD4 and L. gastricus BTM7 indicated maximum tolerance to simulated gastric environment. Both the isolates possessed highest score for cell surface hydrophobicity, cell autoaggregation, adherence to Caco-2 cell lines and antimicrobial activity against clinical isolates of Escherichia coli and Shigella sp. comparable to standard strain of Lactobacillus rhamnosus GG. Further principal component analysis and clustering analysis based on Euclidean Similarity index of probiotic characters revealed that L. paracasei strain CD4 and L. gastricus strain BTM7 were placed closest to reference strain L. rhamnosus GG and were therefore identified as most promising probiotic candidate cultures. CONCLUSIONS: These characteristics suggest that these strains could be excellent candidates for probiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Milk-based products serve as reservoir for bacterial species with probiotic attributes.
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Lacticaseibacillus paracasei/isolamento & purificação , Lactobacillus/isolamento & purificação , Probióticos/isolamento & purificação , Animais , Células CACO-2 , Bovinos , Fermentação , Humanos , Lactobacillus/classificação , Lactobacillus/genética , Lactobacillus/metabolismo , Lacticaseibacillus paracasei/classificação , Lacticaseibacillus paracasei/genética , Lacticaseibacillus paracasei/metabolismo , Leite/microbiologia , Análise de Componente PrincipalRESUMO
AIM: To study the effect of ketoacidosis on measured 25-hydroxyvitamin D3 in children with new onset Type 1 diabetes. METHODS: Measurement of pH and bicarbonate levels was carried out in children with newly diagnosed Type 1 diabetes at presentation with ketoacidosis. 25-hydroxyvitamin D3 estimation was carried out at presentation (timepoint 1) and 1 month later (timepoint 2). There was no significant difference in the mean (±sd) 25-hydroxyvitamin D3 levels [35.39 (±25.79) vs 39.63 (±48.03) nmol/L; P = 0.661) at the two timepoints in the study. RESULTS: Correlation analysis revealed a positive correlation between bicarbonate levels and timepoint 1, i.e. the lower the bicarbonate levels, the lower were the timepoint 1 levels and vice versa (correlation coefficient 0.538, P = 0.001). Timepoint 2 levels also showed a positive correlation with serum bicarbonate levels with a correlation coefficient of 0.379 (P = 0.032). None of the variables other than bicarbonate,.(age, gender, BMI, pH or time), was found to have the predictive ability for timepoint1 levels. Similarly for predicting timepoint 2 levels, BMI was found to have independent predictive ability in addition to bicarbonate. CONCLUSIONS: Severe ketoacidosis, as judged by bicarbonate but not pH, may transiently lower 25-hydroxyvitamin D3 levels in children with new onset Type 1 diabetes. Persistence of low 25-hydroxyvitamin D3 levels after resolution of ketoacidosis suggests a state of permanent vitamin D deficiency in our patient population.
Assuntos
Calcifediol/sangue , Diabetes Mellitus Tipo 1/sangue , Cetoacidose Diabética/sangue , Cetoacidose Diabética/terapia , Bicarbonatos/sangue , Índice de Massa Corporal , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Lactente , Masculino , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicaçõesAssuntos
Hemorragia/induzido quimicamente , Doenças da Unha/induzido quimicamente , Selênio/intoxicação , Dermatopatias/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Doença Crônica , Feminino , Hemorragia/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Unha/complicações , Dermatopatias/complicações , Adulto JovemRESUMO
Air pollution affects not only the air quality in megacities but also in medium and small-sized cities due to rapid urbanization, industrialization, and other anthropogenic activities. From October 28, 2015 to November 3, 2015, the Indo-Gangetic Plains region, including Chandigarh encountered an episode of poor visibility during the daytime. The daily average PM2.5 concentration reached 191 µg/m3, and visibility reduced by â¼2.2 times in the Chandigarh region. PM2.5 concentration was found around 4 times higher than a non-haze day and more than 3 times higher than National Ambient Air Quality Standards for 24 h. A significant correlation between PM2.5 and CO (r: 0.87) during the haze period indicated similarity in their emission sources; which was attributed to the burning of solid organic matter. Further, satellite data and back-trajectory analysis of air masses showed large-scale rice stubble burning in the agricultural fields, adjoining to the city areas. The transboundary movement of air masses below 500 m and meteorological conditions played a major role in building the pollution load in the Chandigarh region. Moreover, the enhanced concentration of biomass burning tracers, i.e., organic carbon (â¼3.8 times) and K+ ions (2â¼ times) in PM2.5 and acetonitrile (â¼2.3 times) in ambient air was observed during the haze event. The study demonstrates how regional emissions and meteorological conditions can affect the air quality in a city; which can be useful for proper planning and mitigation policies to minimize high air pollution episodes.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Cidades , Monitoramento Ambiental , Índia , Meteorologia , Material Particulado/análise , Estações do AnoRESUMO
The present work is aimed to analyze aerosols optical properties and to estimate aerosol radiative forcing (ARF) from January to December 2013, using sky radiometer data over Rohtak, an urban site in North-Western India. The results reveal strong wavelength dependency of aerosol optical depth (AOD), with high values of AOD at shorter wavelengths and lower values at longer wavelength during the study period. The highest AOD values of 1.07 ± 0.45 at 500â nm were observed during July. A significant decline in Ångström exponent was observed during April-May, which represents the dominance of coarse mode particles due to dust-raising convective activities. Aerosols' size distribution exhibits a bimodal structure with fine mode particles around 0.17â µm and coarse mode particles with a radius around 5.28â µm. Single scattering albedo values were lowest during November-December at all wavelengths, ranging from 0.87 to 0.76, which corresponds to the higher absorption during this period. Aerosols optical properties retrieved during observation period are used as input for SBDART (Santa Barbara DISORT Atmospheric Radiative Transfer) to estimate the direct ARF at the surface, in the atmosphere and at the top of the atmosphere (TOA). The ARF at the TOA, surface and in the atmosphere are found to be in the range of -4.98 to -19.35â Wâ m-2, -8.01 to -57.66â Wâ m-2 and +3.02 to +41.64â Wâ m-2, respectively. The averaged forcing for the whole period of observations at the TOA is -11.26â Wâ m-2, while at the surface it is -38.64â Wâ m-2, leading to atmospheric forcing of 27.38â Wâ m-2. The highest (1.168â Kâ day-1) values of heating rate was estimated during November, whereas the lowest value (0.084â Kâ day-1) was estimated for the February.
Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Cidades , Monitoramento Ambiental , Temperatura Alta , Índia , Modelos Teóricos , Fenômenos Ópticos , Radiometria , Estações do AnoRESUMO
The present study was conducted to find out any alteration in the expression and activity of alkaline phosphatase in the brush border membrane (BBM) from renal cell carcinoma (RCC) in comparison to normal renal BBM. The specific activity of alkaline phosphatase was drastically reduced in homogenate as well as BBM from RCC kidney when compared to ALP activity in BBM of normal kidney. Kinetic studies revealed that diminished activity of alkaline phosphatase in BBM isolated from RCC was fraternized with decrease in maximal velocity (V(max)) and increase in affinity constant (K(m)) of the enzyme. SDS-PAGE studies showed that the BBM proteins having molecular weights ranging from 95 to 170 kDa were poorly expressed in RCC BBM in relative to normal kidney BBM. Incubation of SDS-PAGE gel with BCIP/NBT dye clearly showed that the expression of ALP in tumor renal BBM was markedly reduced as compared to normal kidney. Further, Western blot analysis using anti-alkaline phosphatase antibody also confirmed the reduced expression of ALP in tumor renal BBM. Lipid composition in reference to phospholipids, glycolipids and cholesterol in tumor renal BBM was altered to that of normal renal BBM, indicating alteration in membrane fluidity of tumor renal BBM.
Assuntos
Fosfatase Alcalina/metabolismo , Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , Túbulos Renais Proximais/ultraestrutura , Adulto , Idoso , Western Blotting , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Índia , Túbulos Renais Proximais/metabolismo , Masculino , Microvilosidades/metabolismo , Pessoa de Meia-IdadeRESUMO
AIM: To study the role of N-acetylcysteine (NAC) as a protective agent in rifampicin (RMP)-induced oxidative hepatic injury of young rats. METHODS: Hepatic injury was produced by giving 50 mg/kg body weight/day of RMP for 3 wk. A dose of NAC (100 mg/kg body weight/day) was given in combination with RMP intraperitoneally. Analysis of lipid peroxidation, thiol levels, cytochrome P450, superoxide dismutase (SOD), catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body weight, liver weight and histological observations. RESULTS: RMP exposure resulted in no change in body and liver weight while antioxidative enzymes were altered but the non protein thiol (GSH) status was well preserved. Cytochrome P450 system and peroxidation of lipids were induced by RMP exposure. Partial protection was observed with NAC against RMP-induced changes in liver, which was evidenced from the prevention of increase in lipid peroxidation and the reduction in SOD and catalase enzyme levels. CONCLUSION: NAC protects young rats against RMP-induced oxidative hepatic injury.
Assuntos
Acetilcisteína/farmacologia , Antibióticos Antituberculose/toxicidade , Fígado/efeitos dos fármacos , Rifampina/toxicidade , Animais , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
The role of atmospheric aerosols in climate and climate change is one of the largest uncertainties in understanding the present climate and in capability to predict future climate change. Due to this, the study of optical properties of atmospheric aerosols over a mega city "New Delhi" which is highly polluted and populated were conducted for two years long to see the aerosol loading and its seasonal variability using sun/sky radiometer data. Relatively higher mean aerosol optical depth (AOD) (0.90 ± 0.38) at 500 nm and associated Angstrom exponent (AE) (0.82 ± 0.35) for a pair of wavelength 400-870 nm is observed during the study period indicating highly turbid atmosphere throughout the year. Maximum AOD value is observed in the months of June and November while minimum is in transition months March and September. Apart from this, highest value of AOD (AE) value is observed in the post-monsoon [1.00 ± 0.42 (1.02 ± 0.16)] season followed by the winter [0.95 ± 0.36 (1.02 ± 0.20)] attributed to significance contribution of urban as well as biomass/crop residue burning aerosol which is further confirmed by aerosol type discrimination based on AOD vs AE. During the pre-monsoon season, mostly dust and mixed types aerosols are dominated. AODs value at shorter wavelength observed maximum in June and November while at longer wavelength maximum AOD is observed in June only. For the better understanding of seasonal aerosol modification process, the aerosol curvature effect is studied which show a strong seasonal dependency under a high turbid atmosphere, which are mainly associated with various emission sources. Five days air mass back trajectories were computed. They suggest different patterns of particle transport during the different seasons. Results suggest that mixtures of aerosols are present in the urban environment, which affect the regional air quality as well as climate. The present study will be very much useful to the modeler for validation of satellite data with observed data during estimation of radiative effect.
Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Poluição do Ar/estatística & dados numéricos , Atmosfera/química , Cidades/estatística & dados numéricos , Clima , Mudança Climática , Poeira/análise , Índia , Estações do AnoRESUMO
The ground and vertical profiles of particulate matter (PM) were mapped as part of a pilot study using a Tethered balloon within the lower troposphere (1000m) during the foggy episodes in the winter season of 2015-16 in New Delhi, India. Measurements of black carbon (BC) aerosol and PM <2.5 and 10µm (PM2.5 & PM10 respectively) concentrations and their associated particulate optical properties along with meteorological parameters were made. The mean concentrations of PM2.5, PM10, BC370nm, and BC880nm were observed to be 146.8±42.1, 245.4±65.4, 30.3±12.2, and 24.1±10.3µgm-3, respectively. The mean value of PM2.5 was ~12 times higher than the annual US-EPA air quality standard. The fraction of BC in PM2.5 that contributed to absorption in the shorter visible wavelengths (BC370nm) was ~21%. Compared to clear days, the ground level mass concentrations of PM2.5 and BC370nm particles were substantially increased (59% and 24%, respectively) during the foggy episode. The aerosol light extinction coefficient (σext) value was much higher (mean: 610Mm-1) during the lower visibility (foggy) condition. Higher concentrations of PM2.5 (89µgm-3) and longer visible wavelength absorbing BC880nm (25.7µgm-3) particles were observed up to 200m. The BC880nm and PM2.5 aerosol concentrations near boundary layer (1km) were significantly higher (~1.9 and 12µgm-3), respectively. The BC (i.e BCtot) aerosol direct radiative forcing (DRF) values were estimated at the top of the atmosphere (TOA), surface (SFC), and atmosphere (ATM) and its resultant forcing were - 75.5Wm-2 at SFC indicating the cooling effect at the surface. A positive value (20.9Wm-2) of BC aerosol DRF at TOA indicated the warming effect at the top of the atmosphere over the study region. The net DRF value due to BC aerosol was positive (96.4Wm-2) indicating a net warming effect in the atmosphere. The contribution of fossil and biomass fuels to the observed BC aerosol DRF values was ~78% and ~22%, respectively. The higher mean atmospheric heating rate (2.71Kday-1) by BC aerosol in the winter season would probably strengthen the temperature inversion leading to poor dispersion and affecting the formation of clouds. Serious detrimental impacts on regional climate due to the high concentrations of BC and PM (especially PM2.5) aerosol are likely based on this study and suggest the need for immediate, stringent measures to improve the regional air quality in the northern India.
RESUMO
Particulate matter (PM2.5) samples were collected over Delhi, India during January to December 2012 and analysed for carbonaceous aerosols and inorganic ions (SO4(2-) and NO3(-)) in order to examine variations in atmospheric chemistry, combustion sources and influence of long-range transport. The PM2.5 samples are measured (offline) via medium volume air samplers and analysed gravimetrically for carbonaceous (organic carbon, OC; elemental carbon, EC) aerosols and inorganic ions (SO4(2-) and NO3(-)). Furthermore, continuous (online) measurements of PM2.5 (via Beta-attenuation analyser), black carbon (BC) mass concentration (via Magee scientific Aethalometer) and carbon monoxide (via CO-analyser) are carried out. PM2.5 (online) range from 18.2 to 500.6µgm(-3) (annual mean of 124.6±87.9µgm(-3)) exhibiting higher night-time (129.4µgm(-3)) than daytime (103.8µgm(-3)) concentrations. The online concentrations are 38% and 28% lower than the offline during night and day, respectively. In general, larger night-time concentrations are found for the BC, OC, NO3(-)and SO4(2-), which are seasonally dependent with larger differences during late post-monsoon and winter. The high correlation (R(2)=0.74) between OC and EC along with the OC/EC of 7.09 (day time) and 4.55 (night-time), suggest significant influence of biomass-burning emissions (burning of wood and agricultural waste) as well as secondary organic aerosol formation during daytime. Concentrated weighted trajectory (CWT) analysis reveals that the potential sources for the carbonaceous aerosols and pollutants are local emissions within the urban environment and transported smoke from agricultural burning in northwest India during post-monsoon. BC radiative forcing estimates result in very high atmospheric heating rates (~1.8-2.0Kday(-1)) due to agricultural burning effects during the 2012 post-monsoon season.
Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Material Particulado/análise , Fuligem/análise , Carbono/análise , ÍndiaRESUMO
Rotavirus induced diarrhoea was investigated in neonatal mice. Assessment of oxidative/antioxidative profile was the mechanistic approach to study the nature of injury. Neonatal mice (NMRI strain) were infected orally with the homologous strain of (EB) rotavirus (serotype 3). The peak severity of rotavirus infection was attained on the third day post infection. The whole small intestine of neonatal mice on day 3 post infection was homogenized and analysed for oxidative/antioxidative profile. Glutathione and related thiols were significantly declined in rotavirus infected group. Superoxide dismutase, glutathione peroxidase and glutathione-S-transferase (1-chloro 2, 4 dinitrobenzene) activities were also decreased in the rotavirus infected group. The activities of glutathione reductase and glutathione-S-transferase (ethacrynic acid) however were elevated with rotavirus infection in comparison to the control group. Similarly, ADP-FeCI3, NADPH induced lipid peroxidation was elevated with rotavirus infection. Thus the altered oxidative/antioxidative profile indicated the presence of oxidative stress in the rotavirus infected group and can be postulated to have a prominent role in the pathogenesis of the disease.
Assuntos
Animais Recém-Nascidos/metabolismo , Estresse Oxidativo , Infecções por Rotavirus/metabolismo , Animais , Ensaio de Imunoadsorção Enzimática , Intestino Delgado/metabolismo , Camundongos , Camundongos EndogâmicosRESUMO
The role of N-acetylcysteine (NAC), a glutathione (GSH) precursor, was investigated in protection against isoniazid- (INH) and rifampicin- (RIF) induced oxidative hepatic injury in young Wistar rats. The hepatotoxic dose of INH and RIF was 50 mg kg(-1) day(-1) each and the hepatoprotective dose of NAC was 100 mg kg(-1) day(-1). All drugs were administered intraperitoneally (i.p.) in sterile water (4.0 ml kg(-1) day(-1)) over a period of 3 weeks. Status of oxidative/antioxidative profiles was the mechanistic approach to assess the hepatotoxicity and/or hepatoprotection. The oxidative injury in INH-RIF co-exposed animals was closely associated with significant decline of GSH and related thiols, as well as with compromised antioxidant enzyme system. The oxidative stress was further supported by increased lipid peroxidation observed in these animals. The co-administration of NAC prevented the induction of oxidative stress in INH-RIF co-exposed animals. The amelioration of oxidative stress by NAC was faithfully reflected as normal morphology in these animals, except the presence of mild degree of portal triaditis in one animal co-exposed to INH-RIF and NAC. In contrast, the animals co-exposed to INH-RIF alone showed histological lesions which ranged from intralobular inflammation to patchy necrosis. These results suggest that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by NAC.
Assuntos
Acetilcisteína/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Isoniazida/toxicidade , Estresse Oxidativo , Rifampina/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Sistema Enzimático do Citocromo P-450/metabolismo , Interações Medicamentosas , Injeções Intraperitoneais , Isoniazida/administração & dosagem , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Masculino , Ratos , Ratos Wistar , Rifampina/administração & dosagem , Superóxido Dismutase/metabolismoRESUMO
Status of oxidative/antioxidative profile was the mechanistic approach to inumerate the nature of protection by N-acetylcysteine (NAC) in isoniazid (INH) exposed experimental animals. Analysis of lipid peroxidation, thiol levels, cytochrome P450, superoxide dismutase (SOD), catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body and liver weight of animals and histological observations. Isoniazid exposure to animals resulted in no change in body and liver weights. Thiols, lipid peroxidation, catalase, SOD glutathione peroxidase, reductase, transferase and cytochrome P450 levels were altered with INH exposure. Supplementation of NAC with INH protected the animals against hepatotoxic reactions by minimizing the free radical induced tissue injury and overall maintenance of the endogenous scavengers of free radicals.
Assuntos
Acetilcisteína/farmacologia , Isoniazida/antagonistas & inibidores , Fígado/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Sequestradores de Radicais Livres/metabolismo , Glutationa/metabolismo , Isoniazida/toxicidade , Fígado/lesões , Fígado/metabolismo , Fígado/patologia , Masculino , Oxidantes/toxicidade , Ratos , Ratos WistarRESUMO
The impacts of an early South Asian dust storm that originated over the western part of the Middle East and engulfed northwest parts of India during the third week of March 2012 have been studied at four different stations covering India and Pakistan. The impacts of this dust storm on aerosol optical properties were studied in detail at Delhi, Jodhpur, Lahore and Karachi. The impact could also be traced up to central Himalayan foothills at Manora Peak. During dust events, the aerosol optical depth (AOD) at 500 nm reached a peak value of 0.96, 1.02, 2.17 and 0.49 with a corresponding drop in Ångström exponent (AE for 440-870 nm) to 0.01, -0.02, 0.00 and 0.12 at Delhi, Jodhpur, Lahore and Karachi, respectively. The single scattering albedo (SSA) at 675 nm was relatively lower at Delhi (0.87) and Jodhpur (0.86), with absorption Ångström exponent (AAE) less than 1.0, but a large value of SSA was observed at Lahore (0.98) and Karachi (0.93), with AAE value greater than 1.0 during the event. The study of radiative impact of dust aerosols revealed a significant cooling at the surface and warming in the atmosphere (with corresponding large heating rate) at all the stations during dust event. The effect of this dust storm was also seen at Manora Peak in central Himalayas which showed an enhancement of ~28% in the AOD at 500 nm. The transport of dust during such events can have severe climatic implications over the affected plains and the Himalayas.
RESUMO
The role of oxidative stress as a mechanism of hepatic injury caused by isoniazid (INH) was investigated in young growing rats. The interaction of moderate and severe degree of protein-energy malnutrition (PEM) was also investigated. Hepatic injury was produced by giving 50 mg/kg/day of INH for 2 weeks. Liver showed kupffer cell hyperplasia along with patchy sinusoidal congestion in hematoxylin (H) and eosin (E) staining. However, diffuse microglobules of oil red O' positive fat globules could be demonstrated in frozen sections stained with oil red O'. The concomitant elevation of serum ALT/AST added support to the histopathologic injury. Electronmicroscopic analysis revealed the proliferation of rough endoplasmic reticulum in INH-treated groups. The glutathione and related thiols were decreased significantly by INH both in blood and liver tissues, indicating a decrease in protective mechanism. Glutathione reductase activity was elevated concomitantly in both the tissues. A significant decrease in the activity of glutathione peroxidase and catalase is again indicative of diminished capacity to handle the disposal of hydrogen peroxide (H2O2) and lipid peroxides. All these alterations indicated that the damage to the liver cell could well be operating through the inefficient disposal of superoxides (O-2) and H2O2. A profound decrease in the protective mechanism further aggravated the picture in moderate and severe PEM, which was observed with INH alone.
Assuntos
Hepatopatias/fisiopatologia , Fígado/metabolismo , Estresse Oxidativo/fisiologia , Desnutrição Proteico-Calórica/fisiopatologia , Animais , Doença Hepática Induzida por Substâncias e Drogas , Citoplasma/química , Citoplasma/ultraestrutura , Secções Congeladas , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Isoniazida , Peroxidação de Lipídeos/fisiologia , Fígado/citologia , Fígado/efeitos dos fármacos , Masculino , Microscopia Eletrônica , Oxirredutases/metabolismo , Ratos , Ratos WistarRESUMO
The role of protein and energy malnutrition in the pathogenesis of isoniazid (INH)-rifampicin (RMP) induced hepatic injury was investigated. Status of oxidative/antioxidative profile was the mechanistic approach to enumerate the nature of injury. Weanling rats were fed with ad-libitum quantity of isocaloric diets containing 5% casein based proteins for the production protein and energy malnutrition. INH and RMP (50 mg/kg of each) were injected intraperitonially for a period of two weeks. Analysis of serum transaminases and histopathological observations revealed hepatic injury. Hepatic thiols and blood glutathione were decreased significantly in INH and RMP treated groups. Among antioxidative enzymes, hepatic superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferases (against CDNB and DCNB substrates) showed significant decline of activities in INH and RMP treated groups. The activities of hepatic glutathione reductase, glutathione-S-transferase (against EA substrate) and lipid peroxidation observed significant elevation. A careful comparison of protein and energy restriction revealed a greater degree of oxidative-stress of INH-RMP in protein-restriction.