臺灣博碩士論文加值系統

Abstract
Oxidized frying oil (OFO) has been reported to impair normal physiological functions in humans and animals. Degradation products generated during the frying process may have a toxic effect on the liver and lead to oxidative stress. The aim of this study was to investigate the effect of purple sweet potato leaves (PSPL) on hepatic xenobiotic-metabolizing enzymes and oxidative stress in rats fed with OFO diet. Twenty-four male Wistar rats were divided into three groups and fed with different experimental diets for 2 weeks: Control diet (fresh soybean oil); OFO diet; and OFO plus 5% PSPL diet. Rats fed with OFO diet had an increase in plasma levels of alanine transaminase (ALT) and total cholesterol, as well as hepatic inflammatory cytokines such as IL-1, IL-6, and TNF- compared to rats fed with control diet. However, treatment with PSPL significantly decreased plasma cholesterol and lowered plasma ALT level, but slightly reduced hepatic IL-6 level, compared to treatment with OFO. In addition, hepatic CYP3A, CYP4A and CYP2B activities were significantly higher and CYP1A1 and CYP1A2 activities were significantly lower in OFO group than in control group. Treatment with PSPL reversed the effect induced by OFO by reducing CYP4A and CYP2B activities and increasing CYP1A1 activity. On the other hand, UDP-glucuronyltransferase (UGT) activity was significantly higher after treatment with PSPL. The results from this study indicate that short-term exposure to OFO increases plasma cholesterol, induces inflammation and changes some xenobiotic-metabolizing enzyme activities in the liver, whereas PSPL consumption reduces plasma cholesterol and ALT levels, regulates hepatic CYP enzymes and enhances detoxification by increasing UGT activity.

Abstract
Oxidized frying oil (OFO) has been reported to impair normal physiological functions in humans and animals. Degradation products generated during the frying process may have a toxic effect on the liver and lead to oxidative stress. The aim of this study was to investigate the effect of purple sweet potato leaves (PSPL) on hepatic xenobiotic-metabolizing enzymes and oxidative stress in rats fed with OFO diet. Twenty-four male Wistar rats were divided into three groups and fed with different experimental diets for 2 weeks: Control diet (fresh soybean oil); OFO diet; and OFO plus 5% PSPL diet. Rats fed with OFO diet had an increase in plasma levels of alanine transaminase (ALT) and total cholesterol, as well as hepatic inflammatory cytokines such as IL-1, IL-6, and TNF- compared to rats fed with control diet. However, treatment with PSPL significantly decreased plasma cholesterol and lowered plasma ALT level, but slightly reduced hepatic IL-6 level, compared to treatment with OFO. In addition, hepatic CYP3A, CYP4A and CYP2B activities were significantly higher and CYP1A1 and CYP1A2 activities were significantly lower in OFO group than in control group. Treatment with PSPL reversed the effect induced by OFO by reducing CYP4A and CYP2B activities and increasing CYP1A1 activity. On the other hand, UDP-glucuronyltransferase (UGT) activity was significantly higher after treatment with PSPL. The results from this study indicate that short-term exposure to OFO increases plasma cholesterol, induces inflammation and changes some xenobiotic-metabolizing enzyme activities in the liver, whereas PSPL consumption reduces plasma cholesterol and ALT levels, regulates hepatic CYP enzymes and enhances detoxification by increasing UGT activity.

Table of Contents
LIST OF FIGURES iv
LIST OF TABLES v
LIST OF ABBREVIATIONS vi
Abstract viii
1. INTRODUCTION 1
2. LITERATURE REVIEW 3
2.1. Biotransformation of xenobiotics 3
2.2. The phases of xenobiotics metabolism 4
2.2.1. Phase I enzymes 5
2.2.1.1. Cytochrome P450 (CYP) enzymes 5
2.2.1.2. Flavin-containing monooxygenases (FMOs) 6
2.2.1.3. Hydrolytic enzymes 6
2.2.1.4. Aldehyde Dehydrogenases 7
2.2.2. Phase II reactions 7
2.2.2.1. Glucuronidation 7
2.2.2.2. Sulfation 8
2.2.2.3. Glutathione conjugation 8
2.2.2.4. Acetylation 9
2.3. Antioxidant defense system 12
2.3.1. Enzymatic antioxidants 12
2.3.1.1. Superoxide dismutase (SOD) 12
2.3.1.2. Catalase 12
2.3.1.3. Glutathione peroxidase (GPx) 13
2.3.2. Non-enzymatic Antioxidants 14
2.3.2.1. Vitamin C (Ascorbic Acid) 14
2.3.2.2. Vitamin E (-Tocopherol)
 14
2.3.2.3. Glutathione (GSH) 14
2.4. Oxidative stress 15
2.5. Sweet potato leaves 16
3. MATERIALS AND METHODS 18
3.1. Sweet potato leaves 18
3.2. Determination of total phenolic content of PSPL 18
3.3. Preparation of the oxidized frying oil 18
3.4. Determination of acid value 19
3.5. Diet preparation 19
3.6. Experimental design 20
3.7. Animal study 21
3.7.1. Collection of blood and tissue samples 21
3.8. Biochemical analyses 22
3.8.1. Preparation of liver microsomes 22
3.8.2. Xenobiotic-metabolizing enzyme activity assay 22
3.8.3. Glutathione-S-transferase (GST) activity assay 23
3.8.4. UDP-glucuronosyltransferase (UGT) assay 24
3.8.5. Lipid peroxidation measurement 24
3.8.6. Determination of GSH and GSSG 25
3.8.7. Glutathione peroxidase (GPx) activity assay 25
3.8.8. Glutathione reductase (GRd) activity assay 26
3.8.9. Measurement of vitamin C content 26
3.8.10. Measurement of vitamin E content 27
3.9. Statistical analysis 28
4. RESULTS 29
4.1. Total phenolic content 29
4.2. Acid value of the oils 29
4.3. Food intake, body weight and tissues weight 29
4.4. Effect of PSPL and OFO on plasma biochemical parameters in rats 31
4.5. Lipid profile of rats 32
4.6. Effect of OFO and PSPL on inflammatory cytokines in rats’ liver 32
4.7. Effect of PSPL and OFO on xenobiotic metabolizing enzymes system 33
4.8. Antioxidant defense system activities and TBARS value in the liver and intestine of rats fed the different experimental diets for 2 weeks. 36
5. DISCUSSION 37
5.1. Oils quality 37
5.2. Effect of PSPL and OFO on body and tissue weights 37
5.3. Effect on plasma biochemical parameters 38
5.4. Lipid profile 39
5.5. Inflammatory cytokines in the liver 39
5.6. Effect of OFO and PSPL on xenobiotic-metabolizing enzymes 40
5.7. Effect of OFO and PSPL on antioxidant defense system 41
6. CONCLUSION 43
REFERENCES: 44
APPENDIX 1: Preparation of oxidized frying oil (OFO) 56
APPENDIX 2: CYP enzymes analytical conditions 57

REFERENCES:

Adam, S.K., Soelaiman, I.N., Umar, N.A., Mokhtar, N., Mohamed, N., Jaarin, K. (2008). Effects of repeatedly heated palm oil on serum lipid profile, lipid peroxidation and homocysteine levels in a post-menopausal rat model. McGill J Med. 11:145-151.
Banniste, J., Bannister, W., Rotilio, G. (1987). Aspects of the structure, function, and applications of superoxide dismutase. CRC Crit Rev Biochem. 22: 111-180.
Benedelti, P.C., Di Felice, M., Gentili, V., Tagliamonie, B., Tomassi, G. (1990). Influence of dietary thermally oxidized soybean oil on the oxidative status of rats of different ages. Ann Nutr Metab. 34: 221-231.
Bertz, R.J. and Granneman, G.R. (1997). Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet 32: 210-258.
Bhattacharyya, A., Chattopadhyay, R., Mitra, S. and Crowe, S.E. (2014). Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev 94: 329–354.
Block, G., Patterson, B., Subar, A. (1992). Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer. 18:1–29.
Bundgaard, J.R. and Rehfeld, J.F. (2013). Tyrosylprotein sulfotransferases, in Handbook of Biologically Active Peptides, 2nd Edition.
Bunker, V.W. (1992). Free radicals, antioxidants and ageing. Med Lab Sci. 49: 299–312.
Burke, M. D., Thompson, S., Weaver, R. J., Wolf, C. R. and Mayer, R. T. (1994). Cytochrome P450 specificies of alkoxyresorufin O-dealkylation in human and rat liver. Biochemical Pharmacology 48: 923-936.
Caltagirone, S., Rossi, C., Poggi, A., et al. (2000). Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer. 87: 595–600.
Cao, X., Antonyuk, S.V., Seetharaman, S.V., Whitson, L.J., Taylor, A.B., Holloway, S.P., et al. (2008). Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis. J Biol Chem 283: 16169-77.
Cashman, J.R., Perotti, B.Y.T., Berkman, C.E., Lin, J. (1996). Pharmacokinetics and molecular detoxication. Environ Health Perspect. 104: 23–40.
Chang, W.H., Chen, C.M., Hu, S.P., Kan, N.W., Chiu, C.C., Liu, J.F. (2007). Effect of purple sweet potato leaf consumption on the modulation of the antioxidative status in basketball players during training. Asia Pac J Clin Nutr.16: 455–461.
Chang, W.H., Chen, C.M., Hu, S.P., Kan, N.W., Chiu C.C. and Liu, J.F. (2007). Effect of purple sweet potato leaves consumption on the modulation of the immune response in basketball players during the training period. Asia Pac. J. Clin. Nutr. 16: 609–615.
Chang, W.H., Hu, S.P., Huang, Y.F., Yeh, T.S., and Liu, J.F. (2010). Effect of purple sweet potato leaves consumption on exercise-induced oxidative stress and IL-6 and HSP72 levels. J Appl Physiol 109: 1710–1715.
Chao, P.M., Chao, C.Y., Lin, F.J., Huang, C.J. (2001). Oxidized frying oil up-regulates hepatic acyl-CoA oxidase and cyptochrome P450 4A1 genes in rats and activates PPAR. J Nutr. 131: 3166-3174.
Chelikani, P., Fita, I., Loewen, P.C. (2004). Diversity of structures and properties among catalases. Cell Mol Life Sci 61:192-208.
Chen, C.M., Li, S.C., Chen, C.Y., Au, H.K., Shih, C.K., Hsu, C.Y. and Liu, J.F. (2011). Constituents in purple sweet potato leaves inhibit in vitro angiogenesis with opposite effects ex vivo. Nutr. 27: 1177–1182.
Chen, C.M., Lin, Y.L., Chen, C.Y., Hsu, C.Y., Shieh, M.J., Liu, J.F. (2008). Consumption of purple sweet potato leaves decreases lipid peroxidation and DNA damage in humans. Asia Pac J Clin Nutr. 17:408-414.
Chen, W.A., Chiu, C.P., Cheng, W.C., Hsu, C.K. and Kuo, M.I. (2013). Total polar compounds and acid values of repeatedly used frying oils measured by standard and rapid methods. J Food and Drug Anal. 21: 58-65.
Chen, Y.J., Liu, Y.J., Yang, H.J., Yuan, Y., Liu, F.J., Tian L.X., Liang, G.Y. and Yuan, R.M. (2011). Effect of dietary oxidized fish oil on growth performance, body composition, antioxidant defense mechanism and liver histology of juvenile largemouth bass Micropterus salmoides. Aquac Nutr. 18: 21-31.
Chen,Y.Y., Chen, C.M., Chao, P.Y., Chang, T.J., Liu, J.F. (2005). Effects of frying oil and Houttuynia cordata thunb on xenobiotic-metabolizing enzyme system of rodents. World J Gastr. 11: 389-392.
Choe, E. and Min, D.B. (2007). Chemistry of deep-fat frying oils. J. Food Sci. 72: R77-R86.
Chong Wei Kien and Teng Kim Tiu (2016). Underlying health risks of frying oils: Lipid Ox 65: 14-17.
Chu, Y.H., Chang, C.L., Hsu, H.F. (2000). Flavonoid content of several vegetables and their antioxidant activity. J Sci Food Agriculture. 80: 561–566. 

Chua, L.S. (2014). Review on liver inflammation and anti-inflammatory activity of andrographis paniculata for hepatoprotection. Phytother. Res. 28: 1589–1598.
Croom, E. (2012). Metabolism of xenobiotics of human environments. Progress in Molecular Biology and Translational Sci. 112 ISSN 1877-1173.
Dahm, C.C., Keogh, R.H., Spencer, E.A., et al. (2010). Dietary Fiber and Colorectal Cancer Risk: A Nested Case-Control Study Using Food Diaries. J Natl Cancer Inst. 102: 1–13.
Djurašević, S.F., Djordjević, J., Drenca, T., Jasnić, N. and Cvijić, G. (2008). Influence of vitamin C supplementation on the oxidative status of rat liver. Arch. Biol. Sci., Belgrade, 60: 169-173.
Dobarganes, C. and M?黔quez-Ruiz, G. (2015). Possible adverse effects of frying with vegetable oils. British J Nutr. 113: S49–S57.
Eder, K. (1999). The effect of dietary oxidized oil on lipid metabolic in rats. Lipid. 34: 717-725.
Eder, K. and Stangl G.I. (2000). Plasma thyroxine and cholesterol concentrations of miniature pigs are influenced by thermally oxidized dietary lipids. J Nutr, 130: 116-121.
Edwards, R.L., Lyon, T., Litwin, S.E., Rabovsky, A., Symons, J.D., Jalili, T. (2007). Quercetin reduces blood pressure in hypertensive subjects. J Nutr.137: 2405–2411.
Erickson, D. R. 2007. Production and composition of frying fats, In "Deep Frying ". 2nd ed. pp. 3-22. Erickson, M. D. ed. AOCS Press, Urbana, IL, USA.
Falade, A.O., Oboh, G., Ademiluyi, A.O., Odubanjo, O.V. (2015). Consumption of thermally oxidized palm oil diets alters biochemical indices in rats. Journal of basic and applied science, 4: 150-156.
Findlay, G.M., Draper, H.H., and Bergan, J.G. (1970). Lipids 5: 971.
Fouad, F.M., Shahidi, F., Mamer, O.A. (1995). Comparison of thermally oxidized lipids and acetaminophen with concurrent consumption of ethanol as inducers of liver cirrhosis. J Toxicol Environ Health. 46: 217-232.
Frie, B., Stocker, R., Ames, B.N. (1988). Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci. 37:569–71.
Gaetani, G., Ferraris, A., Rolfo, M., Mangerini, R., Arena, S., Kirkman, H. (1996). Predominant role of catalase in the disposal of hydrogen peroxide within human erythrocytes. Blood 87: 1595-1599.
Goedde, H.W., Agarwal, D.P. (1992). Pharmacogenetics of aldehyde dehydrogenase, in Kalow W (Ed): Pharmacogenetics of Drug Metabolism. New York: Pergamon Press, pp 281–311.
Gonzalez, F.J., Coughtrie, M., Tukey, R.H. (2011). “Drug metabolism” in Brunton, L.L., Chabner, B.A., Knollmann, B.C. Goodman & Gilman’s The Pharmacological Basis of THERAPEUTICS, 12th ed.
Guan, X., Hoffman, B., Dwivedi, C., Matthees, D.P. (2003). A simultaneous liquid chromatography/mass spectrometric assay of glutathione, cysteine, homocysteine and their disulfides in biological samples. J. Pharm. Biomed. Anal. 31: 251–26.1
Guengerich, F.P., Shimada, T. (1991). Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem Res Toxicol. 4: 391-407.
Habig, W.H., Jakoby, W.B. (1981). Assays for differentiation of glutathione S- transferases. Methods Enzymol. 77: 398–405.
Halliwell, B. (1990). How to characterize a biological antioxidant. Free Radic. Res. Commun. 9: 132.
Hayes, J.D., Flanagan, J.U., Jowsey, I.R. (2005). Glutathione transferases. Annu Rev Pharmacol Toxicol. 45: 51–88.
Hein, D.W., McQueen, C.A., Grant, D.M., Goodfellow, G.H., Kadlubar, F.F., Weber, W.W. (2000). Pharmacogenetics of the arylamine N-acetyltransferases: A symposium in honor of Wendell W. Weber. Drug Metab Dispos. 28:1425–1432.
Horgan, V.J., Philpot, J.S.L., Poter, B.W., and Roodyn, D.B. (1957). Biochem. J. 67:551.
Hou, D.X. (2003). Potential mechanisms of cancer chemoprevention by anthocyanins. Curr Mol Med. 3: 149–159.
Huang, C., Cheung, N.S., Lu V.R. (1988). Effects of deteriorated frying oil and dietary protein levels on liver microsomal enzymes in rats. J. Amer. Oil Chemists'' Soc. 65: 1796-1803.
Huang, Z., Wang, B., Eaves, D.H., Shikany, J.M., Pace, R.D. (2007) Total phenolics and antioxidant capacity of indigenous vegetables in the southeast United States: Alabama Collaboration for Cardiovascular Equality Project. Int J Food Sci Nutr. 1–9.
Innami, S., Tabata, K., Shimizu, J. et al. (1998). Dried green leaf powders of Jew’s mellow (Corchorus), persimmon (Diosphyros kaki) and sweet potato (Ipomoea batatas poir) lower hepatic cholesterol concentration and increase fecal bile acid excretion in rats fed a cholesterol-free diet. Plant Foods Hum Nutr. 52: 55–65.
Islam, I., Shaikh A.U., Shahidul, I.M. (2009). Antioxidative and antimutagenic potentials of phytochemicals from Ipomoea batatas (L.). Intl J Cancer Res. 5: 1–12.
Islam, M.S., Yoshimoto, M., Terahara, N., Yamakawa, O. (2002). Anthocyanin compositions in sweet potato (Ipomoea batatas L.) leaves. Biosci Biotechnol Biochem, 66: 2483–2486.
Izaki, Y., Yoshikawa, S., Uchiyama, M. (1984). Effect of ingestion of thermally oxidized frying oil on peroxidative criteria in rats. Lipids, 19: 324e31.
Jaarin, K., Yeen, C.P. and Masbah, N. (2016). Consumption of heated palm oil and its effect on kidney in rats. Pakistan J Nutr. 15: 148-154.
Jancova, P., Anzenbacher, P., Anzenbacherova, E. (2010). Phase II drug metabolizing enzymes. Biomedical papers of the medical faculty of the university palacky, Olomouc, Czechoslovakia, 154:103-116
Johnson, M. and Pace, R.D. (2010). Sweet potato leaves: properties and synergistic interactions that promote health and prevent disease. Nutr Rev. 68: 604–615.
Johnston, D.E. (1999). Special considerations in interpreting liver function tests. Am Farm Physic. 59: 23-30.
Jung, U.J., Lee, M.K., Park, Y.B., Jeon, S.M., Choi, M.S. (2006). Antihyperglycemic and antioxidant properties of caffeic acid in db/db mice. J Pharmacol Exp Ther. 318:476–483.
Karlsen, A., Retterstol, L., Laake, P., et al. (2007). Anthocyanins inhibit nuclear factor-kappaB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults. J Nutr.137: 1951–1954.
Kaunitz, H. (1967). Nutritional aspects of thermally oxidized fats and oils. Food Technol. 21: 278-282.
Keller, U., Brandsch, C., Eder, K. (2004). Supplementation of vitamins C and E increases the vitamin E status but does not prevent the formation of oxysterols in the liver of guinea pigs fed an oxidised fat. Eur J Nutr, 43:353-359.
Kelly, F.J. (2003). Oxidative stress: Its role in air pollution and adverse health effects. Occup Environ Med. 60: 612–616.
Kiang, T.K.L., Ensom, M.H.H., Chang, T.K.H. (2005). UDP-glucuronosyltransferases and clinical drug-drug interactions. Pharmacol Ther. 106:97–132.
Kien, C.W., Tiu, T.K. (2016). Underlying Health Risks of Frying Oils: Lipid Oxidation. Palm Oil Developments. 65.
Knekt, P., Kumpulainen, J., Jarvinen, R., et al. (2002). Flavonoid intake and risk of chronic diseases. Am J Clin Nutr. 76: 560–568.
Kobayashi, K., Urashima, K., Shimada, N. and Chiba, K. (2002). Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with c-DNA-expressed systems of the rats. Biochemical Pharmacology 63: 889-896.
Koch, A., Ko ̈nig, B., Spielmann. J., et al. (2007). Thermally oxidized oil increases the expression of insulin-induced genes and inhibits activation of sterol regulatory element-binding protein-2 in rat liver. J Nutr. 137: 2018-2023.
Kurata, R., Adachi, M., Yamakawa, O., Yoshimoto, M. (2007). Growth suppression of human cancer cells by polyphenolics from sweet potato (Ipomoea batatas L.) leaves. J Agric Food Chem. 55: 185–190.
Lalas, S. 2008. Quality of frying oil, In "Advances in Deep-Fat Frying of Foods". pp. 57-75. Sahin, S. and Sumnu, S. G. eds. CRC Press, Boca Raton, FL, USA.
Leong, X.F., M.R. Mustafa, S. Das and K. Jaarin. (2010). Association of elevated blood pressure and impaired vasorelaxation in experimental Sprague-Dawley rats fed with heated vegetable oil. Lipid Health Dis. 9: 66.
Liu, J.F. and Chan, F.C. (2000). Forms of cytochrome P450 in the liver microsome of oxidized frying oil-fed guinea pigs. J Nutr Sci Vitaminol, 46: 240-245.
Liu, J.F. and Huang, C.J. (1995). Tissue alpha-tocopherol retention in male rats is compromised by feeding diets containing oxidized frying oil. J Nutr, 125: 3071-3080.
Liu, J.F. and Huang, C.J. (1996). Dietary oxidized frying oil enhances tissue alpha- tocopherol depletion and radioisotope tracer excretion in vitamin E- deficient rats. J Nutr, 126: 2227-2235.
Liu, T.T., Liang, N.S., Li, Y., Yang, F., Lu, Y., Meng, Z.Q., Zhang, L.S. (2003). Effects of long-term tea polyphenols consumption on hepatic microsomal drug-metabolizing enzymes and liver function in Wistar rats. World J Gastroenterol. 9: 2742-2744.
Low, J., Kapinga, R., Cole, D., Loechl, C., Lynam, J. and Andrade, M. (2009). Unleashing potential of sweet potato in Sub-Saharan Africa: Nutritional impact with orange-fleshed sweet potato leaves (OFSPL). Social Sci. Working Paper, 1: 73-104.
Massaro, M., Scoditti, E., Carluccio, M.A., De Caterina, R. (2008). Basic mechanisms behind the effects of n-3 fatty acids on cardio- vascular disease. Prostag Leukot Essent Fatty Acids. 79: 109–115.
Matousǩová, P., Vokrá̌l, I., Lamka, J. and Skálová, L. (2016). The role of xenobiotic-metabolizing enzymes in anthelmintic deactivation and resistance in helminths. Trends in Parasitology. 32: 481-491.
Mbaeyi-Nwaoha, I.E. and Emejulu, V.N. (2013). Evaluation of phytochemical composition and antimicrobial activity of sweet potato (Ipomoea Batatas) leaf. Pakistan Journal of Nutrition 12: 575-586.
Mezzetti, A., Lapenna, D., Romano, F., Costantini, F., Pierdomenico, S.D., et al. (1996). Systemic oxidative stress and its relationship with age and illness. J Am Geriatr Soc. 44: 823–827
Mohandas, J., Marshall, J.J., Duggin, G.G., Horvath, J.S., Tiller, D.J. (1984). Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer. Cancer Res. 44, 5086–5091.

NCI (2018). Glutathione. Retrieved from https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C523.
Nelson, D.R., Koymans, L., Kamataki, T., Stegeman, J.J., Feyereisen, R., Waxman, D.J., Waterman, M.R., Gotoh, O., Coon, M.J., Estabrook, R.W., Gunsalus, I.C. and Nebert, D.W. (1996). P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharm 6: 1- 42.
Parkinson, A. (2010). “Biotransformation of xenobiotics” in Curtis D. Klaassen, John B. Watkins III. Casarett & Doull''s Essentials of Toxico, 2d ed. 133-224.
Pereira, M.A., O’Reilly, E., Augustsson, K., et al. (2004). Dietary fiber and risk of coronary heart disease: A pooled analysis of cohort studies. Arch Intern Med. 164: 370–376.
Philpott, M., Gould, K.S., Lim, C., Ferguson, L.R. (2004). In situ and in vitro antioxidant activity of sweetpotato anthocyanins. J Agric Food Chem. 52: 1511-3.
Poloyac, S. M., Tortorici, M. A., Przychodzin, D. I., Reynolds, R. B., Xie, W., Frye, R. F. and Zemaitis, M. A. (2004). The effect of isoniazid on CYP 2E1 and CYP 4A- mediated hydroxylation of arachidonic acid in the rat liver and kidney. Drug Metabolism 32: 727-733.
Porter, T.D., Coon, M.J. (1991). Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J Biol Chem. 266: 13469-13472.
Rao, A.V., Rao, L.G. (2007). Carotenoids and human health. Pharmacol Res. 55: 207–216.
Runnie, I., Salleh, M.N., Mohamed, S., Head, R.J., Abeywardena, M.Y. (2004). Vasorelaxation induced by common edible tropical plant extracts in isolated rat aorta and mesenteric vascular bed. J Ethnopharmacol. 92: 311– 316.
Salleh, M.N., Runnie, I., Roach, P.D., Mohamed, S., Abeywardena, M.Y. (2002). Inhibition of low-density lipoprotein oxi- dation and up-regulation of low-density lipoprotein receptor in HepG2 cells by tropical plant extracts. J Agric Food Chem. 50: 3693–3697.
Sies H. (1997). Oxidative stress: Oxidants and antioxidants. Exp Physiol. 82: 291-5.
Sies, M.H., Vernevaut, M.F., Grandgirard, A., Sebedio, J.L. (1988). Induction of hepatic drug-metabolizing enzymes y cyclic fatty acid monomers in the rat. Food Chem Toxico. 26: 9-13.
Staprans, I., Rapp, J.H., Pan, X.M., Hardman, D.A., Feingold, K.R. (1996). Oxidized lipids in the diet accelerate the development of fatty streaks in cholesterol fed rabbits. Artherioscl Throm Vasc Biol. 16: 533-538.
Sturgill, M.G. and Lambert, G.H. (1997). Xenobiotic-induced hepatotoxicity: mechanisms of liver injury and methods of monitoring hepatic function. Clin Chem. 43(8 Pt 2):1512-1526.
Sugiyama, T., Kubota, Y., Shinozuka, K., Yamada, S., Wu, J. and Umegaki, K. (2004) Ginkgo biloba extract modifies hypoglycemic action of tolbutamide via hepatic cytochrome P450-mediated mechanism in aged rats. Life Sciences 75: 1113-1122.
Sülzle, A., Hirche, F., Eder, K. (2004): Thermally oxidized dietary fat upregulates the expression of target genes of PPARα in rat liver. J Nutr. 134:1375-1383.
Surh, Y. (1999). Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat Res. 428: 305–327.
Szaefer, H., J. Jodynis-Liebert, M. Cichocki, A. Matuszewska, and W. Baer-Dubowska (2003). Effect of naturally plant phenolics on the induction of drug metabolizing enzymes by o- toluidine. Toxicology, 186: 67-77.
Tang, Y.L., Huang, C.J. (1998). Dietary oxidized frying oil decreased plasma and liver vitamin A in rats. Nutr Sci J. 23: 265-279.
Traber, M.G., and Atkinson, J. (2007). Vitamin E, antioxidant and nothing more. Free Radic Biol Med 43: 4 –15.
Uchiyama, M. and Mihara, M. (1978). Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Bioch. 86, 271–278.
Ueng, T.H., Kang, J.J., Chao, I.C., Chen, Y.C. (1995) Cytochrome P450: Enzyme regulation and toxicological significance. J Food Drug
Anal, 4: 13-23. 

Varady, J., Gessner, D.K., Most, E., Eder, K. and Ringseis, R. (2012). Dietary moderately oxidized oil activates the Nrf2 signaling pathway in the liver of pigs. Lipids in Health and Dis.11: 31.
Vasiliou, V., Pappa, A., Petersen, D.R. (2000). Role of aldehyde dehydrogenases in endogenous and xenobiotic metabolism. Chemico-Biological Interactions 129: 1–19
Velasco, J., Marmesat, S., Bordeaux, O., Márquez-Ruiz, G., Dobarganes, C. (2004). Formation and evolution of monoepoxy fatty acids in thermoxidized olive and sunflower oils and quantitation in used frying oils from restaurants and fried-food outlets. J. Agr. Food Chem. 52: 4438-4443.
Venkata, R. P., Subramanyam, R. (2016). Toxicology Reports 3, 636–643.
Weickert, M.O., Pfeiffer, A.F. (2008). Metabolic effects of dietary fiber consumption and prevention of diabetes. J Nutr. 138: 439–442.
Williams, R.T. (1971). Detoxification Mechanisms, 2d Edition. New York: Wiley
Woolfe, J.A. (1992). Sweet Potato: An Untapped Food Resource. New York: Cambridge University Press.
Wu, Y.R. (1996). The role of estrogen in the promotional effect of dietary frying oil on mammary tumorigenesis. Doctoral thesis. National Taiwan University, Taipei, Taiwan, R.O.C.
Wuerges, J., Lee, J.W., Yim, Y.I., Yim, H.S., Kang, S.O., Djinovic, C.K. (2004). Crystal structure of nickel-containing superoxide dismutase reveals another type of active site. Proc Natl Acad Sci. 101: 8569-74.
Yao, H.T., Luo, M.N., Lii, C.C. (2015). Chitosan oligosaccharides reduce acetaminophen-induced hepatotoxicity by suppressing CYP-mediated bioactivation. Journal of functional foods. 12: 262–270.
Yamamoto, K., and Niki, E. (1988). Interaction of alpha-tocopherol with iron: antioxidant and prooxidant effects of alpha-tocopherol in the oxidation of lipids in aqueous dispersions in the presence of iron. Biochim Biophys Acta 958: 19 –23.
Yoshikawa, T. and Naito, Y. (2002). What is oxidative stress? Journal of the Japan Med Asso. 45: 271–276.
Yoshimoto, M., Kurata, R., Okuno, S., Ishiguro, K., Yamakawa, O., Tsubata, M., Mori, S., Takagaki. (2005) Nutritional value of and product development from sweet potato leaves. In: 2d International Symposium on Sweet Potato and Cassava, Kuala Lumpur, Malaysia. 183-184.
Yoshimoto, M., Yahara, S., Okuno, S., Islam, M.S., Ishiguro, K., Yamakawa, O. (2002). Antimutagenicity of mono-, di-, and tricaffeoylquinic acid derivatives isolated from sweetpotato (Ipomoea batatas L.) leaf. Biosci Biotechnol Biochem. 66: 36-41.
Zelko, I., Mariani, T., Folz, R. (2002). Superoxide dismutase multigene family: A comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med. 33: 37-49.
Zhou, Z., Wang,Y., Jiang, Y., Diao, Y., Strappe, P., Prenzler, P., Ayton, A., and Blanchard, C. (2016). Deep-fried oil consumption in rats impairs glycerolipid metabolism, gut histology and microbiota structure. Lipids in Health and Dis.15: 86.