Date of Award

2006

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Environmental Science

First Advisor

Dr. Ahmed M. Almehdi

Second Advisor

Dr. Salman Ashraf

Third Advisor

Dr. Zeinab Khalil

Abstract

All organisms including humans are constantly and unavoidably exposed to foreign chemicals (xenobiotics), which include both manufactured and natural molecules such as pollutants and plant metabolites. One such alarming pollutant is lead as it is constantly produced from automobiles exhaust products and food containers. It has been documented that lead, as the major heavy metal pollutant in the air, has notable effects on nervous systems and efficiency of several enzymes.

There are some natural products such as medicinal plants that might have antagonistic effects against such pollutants. Several medicinal plants are used as traditional remedies for many ailments without knowing their detailed biochemical actions at the molecular level.

This work focused on lead toxicity that had been tested in-vitro against some enzymes that are involved in biomolecules synthesis and on enzymes involved in liver detoxication and biotransformation. Furthermore, the antagonistic (or synergestic) effects of some medicinal plants extracts was tested against lead toxicity, as an example of a commonly present heavy metal, with regards to certain metabolic and biotransformation enzymes activities. In addition, enzyme kinetic parameters (Km and Vmax) in relation to substrate binding stoichiometry and inhibition (or activation) were investigated.

In this study, three major enzymes that play important roles in the body were selected. Cytochrome P4502E1 (CYP2E1), Glutathione -S- Transferses (GSTs) enzymes were chosen as representative examples of phase I and phase II of biotransfomation enzymes systems respectively. Nicotinamide-adenine dinucleotide synthetase (NADS) was the third enzyme in our investigation which is involved in Nicotinamide-adenine dinucleotide (NAD+) synthesis. We have selected 4 indigenous species of plants which are commonly used as medicinal plants in the U.A.E for various ailments. These plants are Salvia officinalis, Hibiscus sabdariffa, Chamomilla recutita, and Nigella sativa. Results of this study showed that lead solution inhibited the three sets of enzymes selected for this study in vitro but the extent and sensitivity of such inhibition was different among the studied enzymes systems. The study revealed that increasing the concentrations of the four selected medicinal plants have the ability to decrease the inhibitory effect of lead solution on CYP2E1 activity. GSTs activity was also affected by the medicinal plants extracts within the concentration range used. It has been shown that all the plants extracts revealed inhibitory effects on GSTs activity in vitro. The extent of the inhibitory effect depends on plant species and concentrations of each plant extract. NADS activity in rat liver microsome was determined using High-performance chromatography (HPLC) and the formed NAD+ is separated from the substrates and the other microsome components in Retnetion time (Rt) of 13 minutes. It has been shown that the four plants extracts ameliorated the inhibitory effect of lead on NADS activity when low and high concentrations of each plant extract were used with lead solution. However, these plants extracts alone did not show any significant effect on NADS activity except for Hibiscus sabdariffa extract which caused decreased in NADS activity (11 % inhibition) and such decrease in activity may be due to some active compounds in the plant that cause this decrease in activity in vitro.

Total phenols, flavonoids and proteins were determined and the results revealed that all the plant extracts contain phenolic compounds range from 76.4-28.6 mg GAE/g plant extract) and flavonoids content range from 7.6-28.1 mg QE/g plant extract). The four plants extracts also showed scavenging activity against DPPH free radical which may be related to the phenolic and flavonoids contents of these plants and this may-in part- contribute to the results we obtained in this study regarding lead toxicity and enzymes activities.

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