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Title
DECLARATION
CERTIFICATE
ACKNOWLEDGEMENT
CONTENTS
I. Introduction & Review of Literature
INTRODUCTION
REVIEW OF LITERATURE
1.1 ENVTRONMENTAL RISK FACTORS AND HUMAN HEALTH
1.1.1 CARCINOGENIC AGENTS
1.1.1.1. MYCOTOXINS
Aflatoxins
Acute and chronic effects of aflatoxin in animals
Metabolism of aflatoxin Bl
Aflatoxin and human health
The process of carcinogenesis
1.1.2. PROMOTTNG AGENTS
1.1.3. DIETARY FACTORS AS CHEMOPREVENTIVE AGENTS AGAINST CANCER
Blocking agents
Suppressing agents
Human intervention studies
1.2. INVOLVEMENT OF FREE TADICALS IN THE ACTION OF CERTAIN ENVIRONMENTAL TOXINS
1.2.1. FREE RADICAL - MEDIATED LIPID PEROXTDATTON AND TISSUE DAMAGE
1.2.2 R0LE OF FREE RADICALS IN CARCINOGENESIS
1.2.3. INVOLVEMEIVT OF FREE RADICALS IN OTHER DISEASE PROCESSES
1.3 ANTIOXIDANTS AS INHIBITORS OF FREE RADICALS
1.4. BIOLOGICAL EFFECTS OF THE FOOD ADDITIVES USED IN THE STUDY
(i) Turmeric
(ii) Curcumin (diferuloyl methane)
(iii) Garlic (Allium sativum)
(iv) Asafoetida (Perula asafoetida)
(v) Ellagic acid
(vi) BHA and BHT
II. Materials & Methods
2.1. FOOD ADDITIVES USED IN THE STUDY
2.2. CHEMICALS
2.3. INSTRUMENTS
2.4. CELL LINES USED IN THE STUDY
2.5. ANIMALS
2.6. HUMAN VOLUNTEERS
2.7. TOXIN PR0DUCTION BY Aspergillus parasiticus
2.8. ANTIMUTAGENICITY ASSAY
2.9. INDUCTION OF AFLATOXICOSIS IN DUCKLINGS
2.10. INDUCTION OF HEPATOCARCINOGENESIS IN RATS USING AFB1
2.11. INDUCTION OF FIBROSIS IN RATS
2.12. INDUCTION OF HYPERCHOLESTEROLEMIA IN RATS
2.13. HISTOLOGICAL EXAMINATIONS
2.14. DEMONSTRATION OF T-GLUTAMYL TRANSPEPTIDASE ACTIVITY (GGT) IN LIVER SECTIONS
2.15. Determination of lipid peroxide formation
2.16. DETERMINATION OF SUPEROXIDE FORMATION
2.17. ASSAY FOR LIPID PEROXIDES IN THE SERUM
2.18. ASSAY FOR GLUTAMATE - PYRUVATE TRANSAMINASE (GPT) ACTIVITY
2.19. ASSAY FOR ALKALINE PHOSPHATASE (ALP) ACTIVITY
2.20. ESTIMATION OF PROTEIN IN ANIMAL TISSUES
2.21. ESTIMATION OF HYDROXYPROLINE CONTENT IN ANIMAL TISSUES
2.22. MEASUREMENT OF HAEMOGLOBIN
2.23. ETERMINATION OF TOTAL WBC
2.24. ESTIMATION OF TOTAL CHOLESTEROL LEVELS
2.25. ESTIMATION OF TRIGLYCERIDES IN THE SERUM
2.26. ESTIMATION OF HI) L - AND LDL - CHOLESTEROL
2.27. STATISTICAL ANALYSIS
III. Effect of food additives on aflatoxin - induced toxicities
3.1. METHODS
3.1.1. Preparation of the extracts of food additives
3.1.2. Determination of the effect of food additives on Aflatoxin. production by Aspergillus parasiticus
3.1.3. Determination of the effects of food additives onthe growth of the fungus
3.1.4. Determination of the effects of food additives onthe mutagenicity induced by AFBl
3.1.5. Determination of the effect of food additives on AFB1-induced toxicity in ducklings
3.1.6. Biochemical Analysis
3.1.7. Histological examination
3.1.8. Determination of the effect of food additives on the carcinogenic potential of AFB1
3.2. RESULTS
3.2.1. Effect of food additives on aflatoxin production by A. paraciticus
3.2.2. Effect of food additives on the growth of A.parasiticus
3.2.3. Effect of food additives on the mutagenicity induced by AFBl
3.2.4. The effect of food additives on the hepatotoxicity induced by AFB1 in ducklings
3.2.5. Effect of food additives on the AFB1 - induced histological changes in the liver of ducklings
Fig. 3.2 Effect of additives on the histological changes occured in the liver of ducklings after the administration of AFB1
3.2.6. Effect of food additives on the carcinogenic potential of AFB1
Fig. 3.3 Hepatocellular altered focus in the liver of rat at 28 weeks after the last dose of AFB1
3.3. DlSCUSSION
IV. Effect of food additives on free radical formation and lipid peroxidation
4.1 METHODS
4.1.1. Determination of the effect of food additives on the lipid peroxide formation in vitro
4.1.2. Determination of the effect of food additives on lipoaygenase activity in vitro
4.1.3. Determination of the effect of food additives on superoxide production in vitro
4.1.4. Evaluation of the modulatory effect of curcumin on the lipid peroxide level in human volunteers
4.2. RESULTS
4.2.1. Effect of food additives on lipid peroxide formation in vitro
4.2.2. Effect of food additives on the action of lipoxygenase
4.2.3. Effect of food additives on superoxide formationin vitro
4.2.4. Effect of curcumin on the lipid peroxide level in human volunteers
4.3. DISCUSSION
V. Effect of curcumin on the tissue damages induced by xenobiotics
5.1. METHODS
5.1.1. Determination of the effect of curcumin on CCI4 induced liver fibrosis
5.1.2. Determination of the effect of curcumin on ethanol - induced liver fibrosis
5.1.3. Determination of the effect of curcumin onparaquat - induced lung fibrosis
5.1.4. Determination of the effect of curcumin and ellagic acid on cotton pellet-induced granuloma formation
5.1.5. Biochemical analyaea
5.1.6. Histological examination
5.1.7. Statistical evaluation
5.2. RESULTS
5.2.1. Effect of curcumin on Carbon tetrachloride induced liver fibrosis
5.2.2. Effect of curcumin on ethanol induced liver damage
Fig. 5.1. Effect of curcumin on the fibrosis induced in the liver of rais by the chronic administration of CCI4
Fig. 5.2. Effect of curcumin on the fibrosis Induced in the liver of rats by the chronic administration of ethanol
5.2.3 Effect of curcumin administration on paraquatinduced lung toxicity
Fig. 5.3. Effect of curcumin on the lung toxicity induced by paraquat in rats
5.2.4. Effect of curcumin and ellagic acid on cotton pellet-induced granuloma formation
5.3. DISCUSSION
VI. Effect of curcumin on the cholesterol levels in animals and human volunteers
6.1. METHODS
6.1.1. Determination of the effect of curcumin on cholesterol synthesis using L 929 cells
6.1.2. Determination of the effect of curcumin onhypercholesterolernia in rats
6.1.3. Biochemical analysis
6.1.4. Histological observations
6.1.5. Determination of the effect of curcumin on the lipid profile of human volunteers
6.2. RESULTS
6.2.1. Effect of curcumin on cholesterol synthesis &Ivitro
6.2.2. Effect of curcumin on hypercholesterolemia induced in rats
6.2.3. Effect of curcumin administration on the histological changes in hypercholesterolemic rats
6.2.4. Effect of curcumin administration on serum lipid profile of human volunteers
Fig. 6.2. Effect of curcumin on the histological changes occured in the liver of fat administered with hyperlipidemic diet.
Fig. 6.3. Effect of curcumin on the histological changes occured in the aorta of rats administered with hyperlipidemic diet
6.3. DISCUSSION
VII. Summary and Conclusion
BIBILIOGRAPHY
List of Publications