To Study the Effect of Salts and Complexes of Palladium and Vanadium Metals on the Status of Thiols in Blood Components  Pharmacological and Toxicological Perspectives

Abstract

The selected metalloelements i.e. Vanadium and Palladium have a number of potential Pharmaco-clinical advantages. Vanadium decreases the level of glucose and cholesterol, improves the function of hemoglobin and myoglobin and has anti-cancerous and diuretic functions. Similarly, Palladium compounds have antiviral, antibacterial, neuroprotective and antitumor properties. However studies have also indicated some mild to serious toxic effects of these metalloelements. Biothiols are important antioxidant that provides protection against metals toxicity. The interaction of metalloelements with biothiols can provide valuable information about the level of toxicity of the metalloelements and about the protective role of biothiols thereof. In this piece of work the effect of salts and complexes of Vanadium and Palladium on the status of different thiols (GSH, NAC, D-Pen and albumin) in aqueous medium, blood components and liver homogenate . The thiol quantification was carried out using Elman’s method through UV-visible spectrophotometry and 1H- NMR. Results of the study performed in aqueous medium, as shown in chapter 2, showed that level of different thiols depleted after the addition of the inorganic salts and organic complexes of Vanadium and Palladium. Such depletion was further enhanced with increasing concentrations of the metalloelements and with time incubation. We also observed a maximum depletion in the levels of different thiols at pH 7.6 which is near to physiological pH. Similar observations were also made in blood components as mention in chapter 3. We observed a decrease in the level of Glutathione under the effect of the said metalloelements in whole blood as well as in separated plasma and cytosolic fraction. Observations were also made under different concentrations of the metalloelements, time and pH parameters. Results were showing that the effect of these metalloelements on the level of GSH in blood components is high at pH 7.6 and increases with increasing concentrations of the metalloelements and with time elapse. Such depletion in cytosolic fraction, in particular, is indicative of the fact that the anions of both the metals can cross the membrane of the erythrocytes. Effect of metalloelements Vanadium and Palladium on the status of Glutathione in WBCs (Lymphocytes, B-cells, T-cells and Neutrophils) was also investigated as mention in chapter 4. The results showed that the level of Glutathione in the selected types of WBC’s was depleted as a result of interaction with Vanadium and Palladium. This depletion was further aggravated with increasing concentrations of Palladium and Vanadium, time elapse as well as at pH 7.6. The effect these metalloelements on the concentration of Glutathione in liver homogenate, under different parameters was also observed as mention in chapter 5.for this purpose liver homogenate was prepared according to the protocol established by Schiefer. We observed that the metalloelements decreases the level of Glutathione in the liver homogenate sample which was further enhanced with elevated concentrations of the metals, time incubation and was high at pH7.6. The mechanism of interaction of Palladium with thiols was examined using H-NMR as mentioned in chapter 6. The results revealed that five species are produced during the quantification of thiols with Elman’s reagents (ESSE). These species were ES-, ESSE, ESSR, RSSR and RSH. The results further indicate that the depletion in the level of thiols may be due to 1:1 or 1:2 conjugation of Palladium with thiols respectively. The bonding strength of both the elements with albumin and exchange reaction by low molecular weight thiols were also examined as mentioned in chapter 7. The UV- visible spectrophotometric observation was made at wavelength ranging from 240nm to 500nm. A negligible absorbance was observed at 412nm which suggested that there was no exchange reaction between albumin metal complexes and low molecular weight thiols. The finding of the study suggests that the metalloelements Vanadium and Palladium conjugate with different thiols in aqueous medium, blood components and liver homogenate. The chances of such assumed conjugation reactions further increases with time elapse, with increasing concentration of the metalloelements and in suitable conditions of pH 7.6. These conjugation reactions further suggest that the metalloelements Vanadium and Palladium have xenobiotic nature causing oxidative stress and thiols play their role in detoxification and biotransformation of these metalloelements. This study perform in situ can be used as a model of in vivo study.