Prasunpriya Nayak

BIOCHEMICAL MARKERS FOR ALCOHOL CONSUMPTION

A variety of laboratory tests are available to assist in the diagnosis of alcohol consumption and related disorders. The levels of intake at which laboratory results become abnormal vary from person to person. Laboratory tests are particularly useful in settings where cooperativeness is suspected or when a history is not available. Several biochemical and hematological tests, such as γ-glutamyltransferase (GGT) activity, aspartate aminotransferase (AST) activity, high-density lipoprotein cholesterol (HDL-C) content of serum, and erythrocyte mean corpuscular volume (MCV) are established markers of alcohol intake. Their validity as markers is based largely on correlations with recent intake at a single time point and on decreases in elevated values when heavy drinkers abstain from alcohol. These readily available laboratory tests provide important prognostic information and should be integral part of the assessment of persons with hazardous alcohol consumption. There are several other markers with considerable potential for more accurate reflection of recent alcohol intake. These include carbohydrate deficient transferrin, β-hexosaminidase, acetaldehyde adducts and the urinary ratio of serotonin metabolites, 5-hydroxytryptophol and 5-hydroxyindoleacetic acid. These markers provide hope for more sensitive and specific aids to diagnosis and improved monitoring for intake.

Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

BackgroundAlteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity.ResultsProtein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area.ConclusionThe alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders.

Response of regional brain glutamate transaminases of rat to aluminum in protein malnutrition.

BackgroundThe mechanism of aluminum-induced neurotoxicity is not clear. The involvement of glutamate in the aluminium-induced neurocomplications has been suggested. Brain glutamate levels also found to be altered in protein malnutrition. Alterations in glutamate levels as well as glutamate-α-decarboxylase in different regions of rat brain has been reported in response to aluminum exposure. Thus the study of glutamate metabolising enzymes in different brain regions of rats maintained on either normal or restricted protein diet may be of importance for understanding the neurotoxicity properties of aluminium.ResultsDietary protein restrictions does not have an significant impact on regional aluminum content of the brain. The interaction of aluminum intoxication and protein restriction is significant in the thalamic area and the midbrain-hippocampal region in cases of glutamate oxaloacetate transaminase. In the case of gluatmate pyruvate transaminase, this interaction is significant only in thalamic area.ConclusionThe metabolism of amino acids, as indicated by activities of specific transaminases, of brain is altered in response to aluminum exposure. These alterations are region specific and are dependent on dietary protein intake or manipulation of the brain amino acid homeostasis.

Conjecturable Role of Aluminum in Pathophysiology of Stroke

Escalated environmental contamination and extensive use of aluminum in the contemporary life made its exposure inevitable. Increased uses of aluminum nanoparticles in health applications are widening its impacts. Targeted accumulation of aluminum in nonrenewable cells of brain has nullified the benefits of restricted bioavailability and assimilation, and lead to the contended involvement of the metal in neurodegenerative disorders. In addition to this, special features of aluminum have coerced to evaluate its influence on the pathophysiology of stroke. The wallops of aluminum on aging, cerebrovascular dysfunction, atherogenesis, blood–brain barrier, matrix metalloproteinases, platelet reaction, and homocysteine are discussed to divulge the ways which can aggravate risk factors of stroke. Region-specific susceptibility of aluminum assails and ischemic stroke are compared to predict the link between these neurodegenerative causations. Sequence of pathophysiological changes in stroke are discussed in terms of energy inadequacy, ion-pump failure, depolarization, alteration in [Ca2+]ICF, mitochondrial dysfunction, excitotoxicity, generation of free radicals and inflammatory mediators, and mechanism of cell death are evaluated with aluminum-mediated similar changes and possible influence of aluminum has been indicated in the stroke pathophysiology. In the same line, positive and negative possibilities of aluminum are also speculated in poststroke neuroresuscitation and postconditioning neuroprotection.

Oxidant handling by hippocampus and Hebb-William maze performance in aluminum-exposed albino Wistar rats

Background and Aim: Extensive use of aluminum in modern life made its exposure unavoidable. Hippocampus, a crucial brain structure involved in cognitive function is one of the preferred sites of aluminum accumulation. Oxidative stress was a common observation in neurodegenerative disorder (NDD) and aluminum toxicity. Therefore, the present study was planned to evaluate the association between oxidant handling capacity of hippocampus and aluminum-induced neurotoxicity. Methods: Groups of 6 Wistar rats were administered with aluminum and concomitant exposure to different doses of pro-oxidant (ethanol) for 4 weeks. Neurobehavioral performances in Hebb-William Maze (HWM) were evaluated weekly. Oxidative stress and oxidant handling capacity of hippocampus were evaluated biochemically. Degenerative changes and deposition of aluminum in hippocampus was studied histologically. Two-way analysis of variance (ANOVA) with replication and Tukeys honest significant difference (HSD) test were performed for intergroup differences. Results: Progressive deterioration of HWM performances was noted during the study period. Degenerative changes were boosted by aluminum and ethanol exposure but there was no indication of ethanol-induced enhancement of aluminum accumulation. No significant alteration in hippocampal oxidative stress parameter was observed upon exposure to either aluminum alone or in presence of pro-oxidant dominance. Conclusion: The current dose and duration of aluminum exposure neither altered the oxidant status of rat hippocampus nor its oxidant handling capacity. Presence of concomitant exposure to ethanol caused decrement of superoxide and peroxide handling capacity (SPHC), in lower doses but not in higher doses, which demonstrated higher degree of degenerative changes. Therefore, the oxidative stress is not the only mechanism leading to hippocampal degeneration; in fact it might be a signaling mechanism to prevent oxidative stress faced by hippocampus.

Pro-oxidant status based alterations in cerebellar antioxidant response to aluminum insult

Cerebellum is unique in restraining amyloid-induced neurodegenerative changes. Amyloidosis and oxidant imbalance is common in aluminum exposure. Interestingly, aluminum itself does not pose any redox activity still it is associated with oxidant imbalance, and, it can aggravate the situation of already existing oxidant threat. Male rats were exposed to aluminum for 4 weeks along with exposure to 4 different doses of ethanol. After the treatment period, cerebellar level of protein, reduced glutathione (GSH), lipid perioxidation (TBARS) were measured. Activities of catalase, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione perioxidase (GPx) were also estimated from the homogenized cerebellar tissue. In the present regimen of aluminum exposure, the cerebellum has shown significant reduction only in GPx activity. However, when aluminum was coexposed with ethanol, it contributed significantly to increase the cerebellar oxidant imbalance by (a) compromising the GSH restoration system, (b) reducing enzymatic peroxide scavenging system of cerebellum, (c) restricting the capability to cope with oxidative stress, as well as (d) downgrading the resistance to oxidative damage in response to chemical stress. Present study demonstrates that coexposure of aluminum with pro-oxidant favored development of aluminum-induced oxidative stress in cerebellum. These observations enlighten the role of pro-oxidants in the process of oxidative degeneration of cerebellum. With further studies, the present observation can be useful to understand the mechanism of neurodegenerative disorders and ways to ameliorate them.

Impact of Coexposure to Aluminum and Ethanol on Phosphoesterases and Transaminases of Rat Cerebrum

Impact of Coexposure to Aluminum and Ethanol on Phosphoesterases and Transaminases of Rat Cerebrum Ubiquitous presence along with uncontrolled use of aluminum and increasing trends of ethanol consumption in India increased the chance of coexposure to aluminum and ethanol. Possibilities are there, that both of them follow common mechanisms to produce neurotoxicity. The phosphomonoesterases and glutamate transaminases are studied in rat brain cerebrum after combined exposure to aluminum and varied doses of ethanol for 4 weeks. Dose dependent decreases in growth have been observed. The impact of aluminum on cerebral acidic and alkaline phosphomonoesterases activities were shown to be altered in a dose dependent fashion by the coexposure to ethanol. Aspartate aminotransferase and alanine aminotransferase of the cerebrum were responding differentially to aluminum exposure in the presence of different doses of ethanol exposure. It has been suggested that the ethanol-induced augmentation of impacts of aluminum on the cerebrum is dose dependent and there might be a critical level of ethanol exposure for the observed effect on cerebrum. Uticaj Dvostruke Izloženosti Aluminijumu i Etanolu na Fosfoesteraze i Transaminaze u Mozgu Pacova Sveprisutnost aluminijuma uz njegovu nekontrolisanu upotrebu kao i trend sve veće konzumacije etanola u Indiji povećali su mogućnost dvostruke izloženosti aluminijumu i etanolu. Moguće je da oba prate zajedničke mehanizme u proizvodnji neurotoksičnosti. Fosfomonoesteraze i glutamat-transaminaze ispitivane su u velikom mozgu pacova posle kombinovane izloženosti aluminijumu i različitim dozama etanola tokom 4 nedelje. Uočena su smanjenja rasta zavisna od doze. Pokazano je da se uticaj aluminijuma na aktivnosti moždane kisele i alkalne fosfomonoesteraze menja u zavisnosti od doze usled dvostruke izloženosti etanolu. Aspartat-aminotransferaza i alanin-aminotransferaza u velikom mozgu davale su različit odgovor na izloženost aluminijumu u prisustvu različitih doza izloženosti etanolu. Pokazano je da pojačanje uticaja aluminijuma na mozak izazvano etanolom zavisi od doze i da za opaženi efekat na mozak može postojati kritičan nivo izloženosti etanolu.

Influence of ethanol on aluminum-induced alterations in oxidative stress of rat thalamic area

Background: Neurotoxic impacts of aluminum are associated with oxidant imbalance and implicated in many senile neurodegenerative disorders. Thalamus is relatively protected from aging-related issues, however, seldom studied. Aims: The study is aimed to find out the aluminum-induced oxidative stress in thalamic area and the influence of ethanol on that. Settings and Design: Influence of aluminum on oxidative stress parameters in the thalamic area has been studied in the presence of varied levels of ethanol exposures. Materials and Methods: Male Wistar rats were exposed to aluminum (10 mg/kg bw) and ethanol (0.8-1.6 g/kg bw). Thalamic levels of reduced glutathione (GSH) and lipid peroxidation thiobarbituric acid reactive substances (TBARS) were studied, along with the activities of superoxide dismutase (SOD), catalase, glutathione peroxidise (GPx), and glutathione reductase (GR). Statistical Analysis Used: The data were statistically analyzed using Kruskal-Wallis test for variance and the significance of the difference between groups was studied using Mann-Whitney U test. Results: Lone aluminum exposure failed to produce any alterations in all the tested parameters, except the GPx activity of thalamic area. Nevertheless, concomitant ethanol exposure caused significant alterations in those thalamic parameters barring GSH level and SOD activity. Maximum response was observed with the highest dose of ethanol exposure. Conclusions: Though thalamic area is reported to be selectively susceptible to aluminum-induced oxidative stress, concomitant presence of pro-oxidant dominance might have augmented the aluminum-induced oxidative stress there. The observation may help to understand the mechanistic riddle of oxidative stress created by aluminum, a redox-inactive metal.