Muhammad Farid Khan

Effect of cisplatin on glutathione redox status in isolated plasma and cytosolic fraction

Cisplatin has been used therapeutically in the treatment of malignant tumors. Meanwhile, the major limitations associated with cisplatin are its side effects in the form of nephrotoxicity, neurotoxicity, emetogensis and emerging resistance. Most of these problems are due to its adverse effects on the body’s endogenous cytoprotective molecules like glutathione (GSH). In current study, the effect of glutathione on the improvement of cisplatin therapy along with control on its growing problem of resistance was emphasized. The effect of cisplatin on the chemical and metabolic status of glutathione was evaluated in human venous blood after its separation in to plasma and cellular fraction using ultra violet (UV)-visible spectrophotometer. The glutathione in isolated plasma and cellular fractions of the blood was exposed to different concentrations of cisplatin. It was found that there was a gradual depletion in the concentration of reduced glutathione. Similarly, time-dependent effect of cisplatin was also evaluated on the status of glutathione, in which positive correlation was found between exposure of glutathione to the given concentrations of cisplatin and the depletion of reduced glutathione as the time passed from 0 to 5 h. This depletion in the concentration of reduced GSH is either due to formation of Pt-SG complex or due to the conversion of this multifunctional molecule (glutathione) to its physiologically inactive disulfide form (GSSG). This study was carried out in vitro, which in principle depicts a model of in vivo reaction. This decrease in blood GSH levels after cisplatin treatment will result in decreased antioxidant capacity of the blood, which in turn will result in numerous pathological conditions.

Glutathione role in gallium induced toxicity

Metallo-elements have strong affinity for sulfhydryl group (-SH) of glutathione (GSH) present in tissues. It is very important and interesting to study the reaction of gallium nitrate and glutathione as biomarker of glutathione role in detoxification and conjugation in whole blood components (plasma and cytosolic fraction). The effect of gallium nitrate different concentrations was examined on GSH present in whole blood components. Decrease in GSH level was dependant on gallium nitrate concentration. The decrease in GSH level of whole blood components was more prominent with the time of incubation of gallium nitrate. Decrease in the concentration of reduced glutathione may be due to the interaction of reduce glutathione and gallium nitrate to form oxidized glutathione (GSSG) or gallium-glutathione complex. This change in GSH metabolic status provides information regarding the role of GSH in detoxification of gallium nitrate. The effect of gallium metal on glutathione in blood components was discussed in this study in in vitro condition as a model for in vivo condition. Key words: Gallium nitrate, reduced glutathione (GSH), whole blood, plasma, cytosolic fraction (CF), oxidized glutathione (GSSG), Di-thiobis- dinitro-benzoic acid (DTNB).

A change in metabolic status of glutathione (γ-L- glutamyl-2-cysteinyl-glycine) in lymphocytes by lead compounds

A spectrophotometric investigation of the interaction and coordination of lead compounds with glutathione (GSH) in lymphocytes of healthy male volunteer venous blood has been described. The present study was designed to provide insight into the proposed mechanism of action of lead acetate {Pb(CH3COO)2} and lead acetylacetonate (C10H14O4Pb) with GSH at molecular level. Lymphocytes were separated from blood of healthy human volunteers. Different concentrations of lead acetate and lead acetylacetonate were used and their concentration, time, pH and temperature dependent effects on GSH level was studied. Ellman’s method was used for the determination of GSH. With lead compounds, a decreased concentration of GSH was found, which further decreased with increasing concentration of lead compounds. A more decrease in GSH concentration was found with time-dependent (0-90 minutes) incubation of lymphocytes with lead compounds. pH, 8.5 and temperature, 45°C have been found to be most favorable for reactions of lead compound with GSH. It may be suggested that changes in GSH status produced by lead compounds could be due to the formation of conjugates (Pb-SG) between GSH and lead compounds or conversion of GSH to oxidized GSH (GSSG) in lymphocytes. The interaction and coordination of lead compounds with sulphur suggest the sulfhydryl (-SH) group to be the coordinating site of GSH.

STUDY OF THE CHEMICAL AND METABOLIC CHANGES IN PLASMA GLUTATHIONE (GSH) OF HUMAN BLOOD AFTER LITHIUM INTRODUCTION

Lithium remains a mainstay in the acute and prophylactic treatment of bipolar affective disorder. It is used in the augmentation of antidepressant treatment and, less frequently, in the augmentation of antipsychotic treatment of schizophrenia. It is reported to have specific anti-suicidal effects. Systematic reviews by the Cochrane collaboration and others have examined the evidence base or its use in these contexts. Thus it is interesting to study the effect of Lithium on the Glutathione. The effect of Lithium on the chemical status of the glutathione in plasma has been studied using Ellman’s method. The effect of Lithium on the chemical status of glutathione was determined in plasma for concentration and time dependent effects. There was found a drastic effect on decreasing the concentration of glutathione in plasma as the concentration is increased and time has passed. The decrease in the Glutathione level was concentration and time of interaction dependent, probably due to oxidation of GSH to corresponding disulphide (GSSG).In this paper the effect of Lithium metal on thiol /GSH level was discussed in vitro, which in principal may present a model of in vivo reaction.

CONCENTRATION AND TIME DEPENDENT EFFECT OF ALUMINIUM METAL ON GLUTATHIONE LEVEL IN PLASMA OF HUMAN BLOOD

Aluminium is an important metalloelement and has many medicinal uses like use of aluminum as an antacid. Thus it is interesting to study the effect of Aluminium on the glutathione (GSH) in vivo conditions. The concentration and time dependent effect of Aluminium on glutathione level in plasma was studied by using Ellman’s method. A drastic effect on decreasing the concentration of glutathione level in plasma was found by increasing the concentration of Aluminium sulphate over the time. The reason could probably be due to oxidation of GSH to corresponding disulphide (GSSG). In this paper the effect of Aluminium metal on thiol/GSH level was discussed in vitro, which in principal may present a model of in vivo reaction