UTMB Department of Pathology

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Molecular Mechanisms of Toxic Action of Xenobiotic Alcohols and Alcoholic Pancreatitis

The primary focus of my research is to understand the molecular mechanisms of toxic action of the xenobiotic alcohols, which involves studies related to metabolomics, toxicokinetics, and biochemical toxicity.

One of the potential mechanism of retention and toxicity of xenobiotics and/or their metabolites is associated with their conjugation with fatty acids and other membrane lipids via non-oxidative metabolism catalyzed by fatty acid ethyl ester synthase. These metabolites have been implicated in the etiology of chronic diseases of substance abuse and environmental exposure. I use state of the art instrumentation such as HPLC, nuclear magnetic resonance and mass spectrometry, and develop analytical methods. These studies are important for elucidating the toxic metabolic pathways of the xenobiotics and/or their metabolites.

Purification and characterization of the enzymes involved in the metabolism of xenobiotics and/or their metabolites are also the part of ongoing research on understanding the mechanism(s) of toxic action of the parent compound. My current research is directed to delineate the molecular mechanism and development of preventive measures of alcoholic pancreatitis and hepatitis.

1. Mericle KA, Kaphalia BS, and Ansari GAS. Modulation of fatty acid methyl esters in rats pretreated with tri-O-tolyl phosphate. J. Toxicol. Environ. Hlth. Part A, 67; 583-593, 2004
2. Li H, Kaphalia BS, Ansari GAS, and Khan MF. Quantitation of acrolein-protein adducts: potential biomarkers of acrolein exposure. J. Toxicol. Environ. Hlth. Part A, 67; 513-524, 2004
3. Kaphalia BS, Mericle KA, and Ansari GAS. Mechanism of Differential Inhibition of Hepatic and Pancreatic Fatty Acid Ethyl Ester Synthase by Inhibitors of Serine-Esterases: In Vitro and Cell Culture Studies. Toxicol. Appl. Pharmacol. 200, 7-15, 2004.
4. Kaphalia BS, and Ansari GAS. Purification and characterization of rat pancreatic fatty acid ethyl ester synthase and its structural and functional relationship to pancreatic cholesterol esterase. J Biochem Mol Toxicol. 17; 338-245, 2003
5. Khan MF, Wu X, Kaphalia BS, Boor PJ, and Ansari GAS. Nitrotyrosine formation in spelenic toxicity of aniline. Toxicology 194: 95-102, 2003.
6. Mericle KA, Kaphalia BS, and Ansari GAS. Differential inhibition of hepatic, pancreatic, and plasma fatty acid ethyl ester synthase by tri-O-tolylphosphate in rats. Toxicol. Appl. Pharmacol. 179, 119-125, 2002
7. Kaphalia BS, and Ansari GAS. Fatty acid ethyl esters and ethanol-induced pancreatitis. Cell. Mol. Biol. 47: OL173-OL179, 2001
8. Kaphalia BS, Khan MF, Green SM, Mericle KA, and Ansari GAS Xenobiotic conjugates of fatty acids. Pharmacology and Therapeutics in the New Millennium. pp 698-706, 2001
9. Green SM, Khan MF, Kaphalia BS, and Ansari GAS. Immunohistochemical localization of trichloroacylated protein adducts in tetrachloroethene-treated rats. J. Toxicol. Environ. Hlth. 63: 145-147, 2001
10. Kaphalia BS, and Ansari GAS. Purification and characterization of rat hepatic microsomal low molecular weight ethyl ester synthase and their relationship to carboxylesterases. J Biochem Mol Toxicol. 15: 165-171, 2001
11. Kaphalia BS, Green SG, and Ansari GAS. Fatty acid ethyl and methyl ester synthases, and fatty acid anilide synthase in HepG2 and AR42J cells: interrelationships and inhibition by tri-o-tolyl phosphate. Toxicol Appl Pharmacol 159: 134-141, 1999
12. Kaphalia BS, Khan MF, and Ansari GAS. Fatty acid anilides: In vivo formation and relevance to Toxic Oil Syndrome. J Biochem Mol Toxicol 13: 269-277, 1999
13. Kaphalia BS, and Ansari GAS. Single step thin-layer chromatographic method for quantitation of enzymatic formation fatty acid anilides. J Chromatogr B. 705:269-275, 1998
14. Hadjipavlou AG, Simmons JW, Young JP, Ansari GAS, Kaphalia BS, Simmons DJ, Nicodemus CL, Lane R, and Esch O. Torsional injury resulting in disc degeneration: an in vivo rabbit model. J Spinal Disorder 11: 312-317, 1998
15. Khan MF, Kaphalia BS, and Ansari GAS. Time-dependent autoimmune response of dichloroacetyl chloride in female MRL +/+ mice. Immunopharmacol Toxicol 19:265-277, 1997
16. Khan MF, Xiaohong W, Kaphalia BS, Boor PJ, and Ansari GAS. Acute hematopoietic toxicity of aniline in rats. Toxicol Lett 92: 31-37; 1997
17. Kaphalia BS, Fritz RR and Ansari GAS. Purification and characterization of rat liver microsomal fatty acid ethyl and 2-chloroethyl ester synthase and their relationship with carboxylesterase (pl 6.1). Chem Res Toxicol 10:211-218, 1997
18. Kaphalia BS, Khan MF, Carroll RM, Aronson J, and Ansari GAS. Subchronic toxicity of 2-chloroethanol and 2-bromoethanol in rats. Res Commun Pharmacol Toxicol 1:173-186; 1996
19. Kaphalia BS, Ghaneyam BJ, and Ansari GAS. Nonoxidative metabolism of 2-butoxyethanol via fatty acid conjugation in Fischer 344 rats. J Toxicol Environ Hlth 49:101-117; 1996
20. Ansari GAS, Kaphalia BS, and Khan MF. Fatty acid conjugates of xenobiotics. Toxicol Lett 75: 1-17; 1995
21. Khan MF, Kaphalia BS, and Ansari GAS. Erythrocyte-aniline interaction leads to their accumulation and iron deposition in rat spleen. J Toxicol Environ Hlth 44: 415-421; 1995
22. Khan MF, Boor PJ, Kaphalia BS, Alcock NW, and Ansari GAS. Hematopoietic toxicity of linoleic acid anilide: Importance of aniline. Fundam Appl Toxicol 25: 224-232; 1995
23. Kapahlia BS, Carr JB, and Ansari GAS. Increased endobiotic fatty acid methyl esters following exposure to methanol. Fundam Appl Toxicol 28: 264-273, 1995
24. Zeng FY, Kaphalia BS, Ansari GAS, and Weigel PH. Fatty acylation of the rat asialoglycoprotein receptor: The three subunits from active receptors contain covalently bound palmitate and stearate. J Biol Chem 270: 21382-21387; 1995
25. Khan MF, Kaphalia BS, Prabhakar BS, Kanz MF, Ansari GAS. Trichloroethene-induced autoimmune response in female MRL +/+ mice. Toxicol Appl Pharmacol 134: 155-160; 1995
26. Khan MF, Kaphalia BS, Boor PJ, and Ansari GAS. Subchronic toxicity of aniline hydrochloride in rats. Arch Environ Contam Toxicol 24: 368-374; 1993
27. Ahmad, F, Kaphalia, BS, Khan, MF and Ansari, GAS. Fatty acid anilides: A new conjugation pathway of aniline. Biochem Arch 9: 111-118; 1993
28. Kaphalia, BS and Ansari GAS. Covalent binding of ethylene dibromide and its metabolites to albumin. Toxicol Lett 62: 221 230; 1992
29. Kanz MF, Kaphalia L, Kaphalia BS, Ramagnoli E, and Ansari GAS. Methylene dianiline: Metabolism and its effects on biliary functions. Toxicol Appl Pharmacol 117: 88-97; 1992
30. Khan MF, Kaphalia BS, and Ansari GAS. Toxic response of linoleic acid anilide in female rats. Res Commun Chem Pathol Pharmacol 77: 241-244; 1992
31. Kaphalia BS, Bhat HK, Khan MF, and Ansari GAS. Tissue distribution of monochloroacetic acid and its binding to albumin in rats. Toxicol Indust Hlth 8: 53-61, 1992.24
32. Kaphalia BS, Khan MF, Boor PJ, and Ansari GAS. Toxic response to repeated oral administration of 2-chloroethyl linoleate in rats. Res Commun Chem Path Pharmacol. 76: 209-222; 1992
33. Kaphalia BS, Khan MF, and Ansari GAS. Reduced activities of serum lactate dehydrogenase and aminotransferases due to an oral administration of 2 chloroethyl linoleate in rats. Bull Environ Contam Toxicol 48: 308-312, 1992
34. Kaphalia BS and Ansari GAS. Rapid Chromatographic analysis of fatty acid anilides suspected of causing toxic oil syndrome. J Anal Toxicol 14: 90-94; 1991
35. Khan MF, Kaphalia BS, Palafox A Jerrells, TR and Ansari GAS. Heated linoleic acid anilide: Toxicity and relevance to toxic oil syndrome. Toxicology, 68:143 155; 1991
36. Kaphalia, BS. Fatty acid conjugates of chlorinated phenols: Synthesis, structural elucidation, and high performance liquid chromatographic analysis. J Chromatogr 537: 85-92; 1991
37. Ansari GAS, Kaphalia BS, and Boor PJ. Palmitoylpentachlorophenol: Formation and toxicity. Proceedings of International Conference on Biomembranes in Health and Disease, Kidwai AM, Upreh RK, Ray PK. (Eds.) Nov. 1-4, 1988 Lucknow, India. 1: 217-224; 1991
38. Boor PJ, Khan MF, Kaphalia BS, Jerrells TR, and Ansari GAS. Synergistic vascular toxicity and fatty acid anilides in the toxic oil syndrome. J Am Coll Cardiol 18: 1824 1828; 1991
39. Khan MF, Kaphalia BS, Palafox A, Jerrells TR, and Ansari GAS. Toxicity of oleic acid anilide in rats. Arch Environ Contam Toxicol 21: 571-577; 1991
40. Khan MF, Kaphalia BS, and Ansari GAS. Treated linoleic acid anilide reduces serum enzyme activities in rats. Res Commun Chem Path Pharm 73: 107-110; 1991
41. Kaphalia, BS and Ansari GAS. Trichloromethyl peroxyl radical (Cl3C00.) mediated oxidation of cholesterol. Chemosphere 20: 5-11; 1990
42. Kaphalia BS, Takroo R, Mehrotra S, Nigam U, and Seth TD. Organochlorine pesticide (OCP) residues in different Indian cereals, spices, vegetables, fruits, milk, butter, deshighee and edible oils. J Assoc Off Anal Chem 73(4): 509-512; 1990
43. Husain, MM and Kaphalia BS. Bioconcentration of cadmium, manganese and lead in some common species of wild birds captured from a semipopulated area in the Indo-Gangetic Plains. J Environ Biol 11: 193-201; 1990
44. Kaphalia BS and Ansari GAS. Hepatic fatty acid conjugation of 2-chloroethanol and 2-bromoethanol in rats. J Biochem Toxicol 4: 183-188; 1989
45. Kaphalia BS and Ansari, GAS. Covalent modification of hepatic microsomal lipids of rats by carbon tetrachloride. Mol Toxicol 2: 199-213; 1989
46. Kaphalia BS, Bhargava SK, Nigam U, and Seth TD. Levels of organochlorine pesticide residues in the water samples collected from Srinagar (J&K), India. Ind J Environ Protect 8: 326-329; 1988
47. Ansari, GAS, Kaphalia BS, and Boor PJ. Selective pancreatic toxicity of palmitoylpentachlorophenol. Toxicology 46: 57-63; 1987
48. Kaphalia, BS and Ansari GAS. 2-Chloroethylesterate: an in vivo fatty acid conjugate of 2-chloroethanol. Bull Environ Contam Toxicol 39: 835-842; 1987
49. Kaphalia, BS, Nigam U, Mehrotra, S, and Seth TD. Freshwater fish: An indicator of pesticide contamination in the aquatic environment. J Environ Biol 7: 1 9; 1986
50. Kar AM, Seth TD, Kaphalia BS, Shukla R, and Nag D. Pesticide contamination of HCH: A possible factor for the altered levels of electrolytes and trace elements in the CSF of epileptic patients. Ind J Med Sci 40: 1-5; 1986
51. Takroo R, Kaphalia BS, and Seth TD. Chlorinated pesticide residues in different brands of butter. J Food Sci Technol 22: 54 59; 1985
52. Kaphalia BS and Seth TD. Chlorinated pesticide residues in human body tissues at autopsy. Pesticides, 19:18-19; 1985
53. Kaphalia BS, Siddiqui FS, and Seth TD. Contamination levels in different food items and dietary intake of chlorinated pesticide residues in India. Ind J Med Res 81:71-78; 1985
54. Ramakrishnan, N, Kaphalia BS, Seth TD, and Roy NK. Organochlorine pesticide contaminants in mother’s milk; a source of toxic chemicals in suckling infants. Human Toxicol 4: 7-12; 1985
55. Kaphalia BS and Seth TD. Screening of blood serum of food animals, chicken and human beings for organochlorine pesticides and electrolytes. Ind J Anim Hlth 23:23-27; 1984
56. Dikshith TSS, Raizada RB, Srivastiva MK, and Kaphalia BS. Response of repeated oral administration of endosulfan in rats. Indust Hlth 22: 295-306; 1984
57. Kaphalia BS and Seth TD. Chlorinated pesticide residues in blood plasma and adipose tissues of normal and exposed human population, Ind J Med Res 77:245 247; 1983
58. Seth TD and Kaphalia BS. Residue levels of DDT in the body tissues of sheep. J Environ Biol 4: 95-97; 1983
59. Kaphalia BS and Seth TD. Organochlorine pesticide contamination in some species of fodder grasses. Environ Pollut 3: 231-237; 1982
60. Kaphalia, BS and Seth TD. DDT and BHC residues in some body tissues of goats, buffalo and chickens. Pest Monit J 15: 103-106; 1981
61. Kaphalia BS, Husain MM, Seth TD, Kumar A, and Krishna Murti CR. Organochlorine pesticide residues in some Indian wild birds. Pest Monit J 15:9 13; 1981
62. Seth TD and Kaphalia BS. 1, 2, 3, 4, 5, 6-Hexachlorocyclohexane (HCH) residues in tissues of sheep. Vet Human Toxicol 23: 247-248; 1981
63. Kaphalia, BS, Chandra H, Bhargava SK, Seth TD, and Gupta BN. Lead in drinking water. Ind J Environ Protect 1: 92-97; 1981
64. Singh S, Tripathi VK, Kaphalia BS, and Seth TD. Residues of endosulfan in/on brinjal fruits. Progr Hort 13: 19-25; 1980

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