M Firoze Khan

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M Khan
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Academic Appointments
Appointment Organization
Professor Pathology
Research Interests

Molecular Toxicology

My research is focused on two major areas: (1) Delineation of molecular mechanisms of splenic toxicity of aromatic amines, and (2) Chemical-induced autoimmunity with special emphasis on the role of oxidative stress.

Exposure to aniline and substituted anilines is associated with splenic toxicity which is characterized by splenomegaly, congestion, hemorrhage, hyperplasia, fibrosis and a variety of sarcomas, most commonly fibrosarcomas. However, the mechanism(s) by which aniline or substituted anilines cause selective splenic toxicity is not well understood. We have shown that aniline exposure in rats results in time- and dose-dependent accumulation of iron in the spleen, which correlates well with the development of fibrotic lesions. Furthermore, our studies show that aniline exposure also results in increases in splenic lipid peroxidation, malondialdehyde (MDA)-protein adducts, DNA oxidation, protein oxidation and nitrotyrosine formation. These studies suggest that increased oxidative stress in the spleen is probably mediated by iron, and could be one of the potential mechanism(s) of splenic toxicity of aniline. Our dose-response studies with phenylhydroxylamine and nitrosobenzene indicated splenotoxic potential of these metabolites at concentrations several fold lower than aniline. Currently, we are focusing on cell signaling mechanisms, fibrogenic cytokines, DNA oxidation and role of reactive nitrogen species in the splenic toxicity of aniline.

The second project focuses on experimental models to study chemical-induced autoimmunity, and to delineate the mechanisms of autoimmunity. Our studies are especially focused on the role of oxidative stress in inducing autoimmune response. Using MRL +/+ mice, we have shown that trichloroethene and one of its metabolites, dichloroacetyl chloride, induce/accelerate autoimmune responses as assessed by the appearance of anti-nuclear-, anti-ssDNA-, anti-cardiolipin-, DCAC-specific-antibodies, and anti-MDA antibodies in the serum. Understanding the cellular events, characterization of antigens and elucidation of various mechanisms in chemical-induced autoimmunity is my long-term objective.

Selected Publications
  1. Wang G, Cai P, Ansari GAS, Khan MF. Oxidative and nitrosative stress in trichloroethene-mediated autoimmune response. Toxicology 229:186-193, 2007
  2. Cai P, Konig R, Khan MF, Kaphalia BS, Ansari GAS. Differential immune responses to albumin adducts of reactive intermediates of trichloroethene in MRL +/+ mice. Toxicol Appl Pharmacol 220:278-283, 2007
  3. Li H, Wang J, Konig R, Ansari GAS, Khan MF. Formaldehyde-protein conjugate specific antibodies in rats exposed to formaldehyde. J Toxicol Environ Health, Part A 70:1071-1075, 2007
  4. Khan MF, Kannan S, Wang J. Activation of transcription factor AP-1 and mitogen-activated protein kinases in aniline-induced splenic toxicity. Toxicol Appl Pharmacol 210:86-93, 2006
  5. Cai P, Khan MF, Konig R, Ansari GAS. Immunotoxic responses of dichloroacetylchloride and dichloroacetic anhydride in female MRL +/+ mice. Toxicol Appl Pharmacol 216:248-255, 2006
  6. Sarkar S, Khan MF, Kaphalia BS, Ansari GAS. Methyl palmitate inhibits lipopolysaccharide-stimulated phagocytic activity of rat peritoneal macrophages. J Biochem Mol Toxicol 20, 302-308, 2006
  7. Wang J, Kannan S, Li H, Khan MF. Cytokine gene expression and activation of NF-κB in aniline-induced splenic toxicity. Toxicol Appl Pharmacol 203:36-44, 2005
  8. Wu X, Kannan S, Khan MF. Iron release and oxidative DNA damage in spleen following aniline intoxication. J Toxicol Environ Health, Part A 68:657-666, 2005
  9. Cai P, Khan MF, Kaphalia BS, Ansari GAS. Immunotoxic response of oleic acid anilide and its hydrolysis products in female MRL +/+ mice. J Immunotox 2:231- 236, 2005
  10. Li H, Wang J, Kaphalia BS, Ansari GAS, Khan MF. Quantitation of acrolein-protein adducts: Potential biomarker of acrolein exposure. J Toxicol Environ Health, Part A 67:513-524, 2004
  11. Kaphalia BS, Cai P, Khan MF, Okorodudu AG, Ansari GAS. Fatty acid ethyl esters in alcoholics:Markers of alcohol abuse and alcoholism. Alcohol 34:151-158, 2004
  12. Khan MF, Wu X, Wang J. Up-Regulation of transforming growth factor-beta 1 in splenic toxicity of aniline. Toxicol Appl Pharmacol: 187: 22-28, 2003
  13. Khan MF, Wu X, Ansari GAS, Boor PJ. Malondialdehyde-protein adducts in the spleens of aniline-treated rats: Immunohistochemical detection and localization. J Toxicol Environ Health, Part A 66: 93-102, 2003
  14. Khan MF, Wu X, Boor PJ, Ansari GAS. Nitrotyrosine formation in splenic toxicity of aniline. Toxicology 194: 95-102, 2003
  15. Khan MF, Wu, X, Tipnis UR, Ansari GAS, Boor PJ. Protein adducts of malondialdehyde and 4-hydroxynonenal in the livers of iron-loaded rats: Quantitation and localization. Toxicology 173:193-201, 2002
  16. Khan MF, Wu X, Ansari GAS. Anti-malondialdehyde antibodies in MR +/+ mice treated with trichloroethene and dichloroacetyl chloride:Possible role of lipid peroxidation in autoimmunity. Toxicol Appl Pharmacol 170:88-92, 2001
  17. Green SM, Khan MF, Kaphalia BS, Ansari GAS. Immunohistochemical localization of trichloroacylated protein adducts in tetrachloroethene-treated mice. J Toxicol Environ Health 63:145-157, 2001.
  18. Khan MF, Wu X, Ansari GAS. Contribution of nitrosobenzene to splenic toxicity of aniline. J Toxicol Environ Health 60:263-273, 2000
  19. Khan MF, Wu X, Boor PJ, Ansari GAS. Oxidative modification of proteins and lipids in aniline-induced splenic toxicity. Toxicol Sci 48:134-140, 1999
  20. Kaphalia BS, Khan MF, Ansari GAS. Fatty acid anilides: In vivo formation and relevance to toxic oil syndrome. J Biochem Mol Toxicol 13:269-277, 1999
  21. Khan MF, Wu X, Alcock NW, Boor PJ, Ansari GAS. Iron exacerbates aniline-associated splenic toxicity. J Toxicol Environ Health 57:173-184, 1999
  22. Khan MF, Green, SM, Ansari GAS, Boor PJ. Phenylhydroxylamine: Role in aniline-associated splenic oxidative stress and induction of subendocardial necrosis in rats. Toxicol Sci 42:64-71, 1998
  23. Tipnis UR, He GY, Khan MF. Differential induction of polyamine oxidase activity in liver and heart of iron-loaded rats. J Toxicol Environ Health 51:235-244, 1997
  24. Khan MF, Gu, Y, Alcock NW, Boor PJ, Ansari GAS. Oxidative stress in splenotoxicity of aniline. Fundam Appl Toxicol 35:22-30, 1997
  25. Khan MF, Wu X, Kaphalia BS, Boor PJ, Ansari GAS. Acute hematopoietic toxicity of aniline in rats. Toxicol Lett 92:31-37, 1997
  26. Khan MF, Kaphalia BS, Ansari GAS. Time-dependent autoimmune response of dichloroacetyl chloride in female MRL+/+ mice. Immunopharmacol Immunotoxicol 19:265-277, 1997
  27. Kaphalia BS, Khan MF, Carrol RM, Aronson J, Ansari GAS. Subchronic toxicity of 2-chloroethanol and 2-bromoethanol in rats. Res Commun Pharmacol Toxicol 1:173-186, 1996
  28. Ansari GAS, Kaphalia BS, Khan MF. Fatty acid conjugates of xenobiotics. Toxicol Lett 75:1 17, 1995
  29. Khan MF, Boor PJ, Kaphalia BS, Alcock NW, Ansari GAS. Hematopoietic toxicity of linoleic acid anilide: Importance of aniline. Fundam Appl Toxicol 25: 224-232, 1995
  30. Khan MF, Kaphalia BS, Ansari GAS. Erythrocyte-aniline interaction leads to their accumulation and iron deposition in rat spleen. J Toxicol Environ Health 44:415-421, 1995
  31. Khan MF, Srivastava SK, Singhal SS, Chaubey M, Awasthi S, Petersen DRR, Ansari GAS, Awasthi YC. Iron induced lipid peroxidation in rat liver is accompanied with preferential induction of glutathione S-transferase 8-8 isozyme. Toxicol Appl Pharmacol 131:63-72, 1995
  32. 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
  33. Khan MF, Kaphalia BS, Boor PJ, Ansari GAS. Subchronic toxicity of aniline hydrochloride in rats. Arch Environ Contam Toxicol 24:368-374, 1993.
  34. Ahmad F, Kaphalia BS, Khan MF, Ansari GAS. Fatty acid anilides: A new conjugation pathway of aniline. Biochem Arch 9:111-118, 1993
  35. Kaphalia BS, Bhat HK, Khan MF, Ansari GAS. Tissue distribution of monochloroacetic acid and its binding to albumin in rats. Toxicol Ind Health 8: 53 61, 1992.
  36. Kaphalia BS, Khan MF, Ansari GAS. Reduced activities of serum lactate dehydrogenase and aminotransferases due to an oral administration of 2 chloroethyllinoleate in rats. Bull Environ Contam Toxicol 48: 308 312, 1992
  37. Khan MF, Kaphalia BS, Ansari GAS. Toxic response of linoleic acid anilide in female rats. Res Commun Chem Pathol Pharmacol 77: 241 244, 1992.
  38. Kaphalia BS, Khan MF, Ansari GAS. Toxic response to repeated oral administration of 2 chloroethyllinoleate in rats. Res Commun Chem Pathol Pharmacol 76:209-222,1992.
  39. Boor PJ, Khan MF, Kaphalia BS, Jerrells TR, Ansari GAS. Synergistic vascular toxicity and fatty acid anilides in the toxic oil syndrome. J Am Coll Cardiol 18:1824 1828, 1991.
  40. Khan MF, Kaphalia BS, Palafox A, Jerrells TR, Ansari GAS. Toxicity of oleic acid anilide in rats. Arch Environ Contam Toxicol 21: 571 577, 1991.
  41. Khan MF, Kaphalia BS, Ansari GAS. Heated linoleic acid anilide reduces serum enzyme activities in rats. Res Commun Chem Pathol Pharmacol 73: 107 110, 1991.
  42. Khan MF, Gupta GSD. Cellular and biochemical indices of bronchoalveolar lavage for the detection of lung injury following insult by airborne toxicants. Toxicol Lett 58:239 255, 1991.
  43. Lemaire I, Jones S, Khan MF. Bombesin like peptides in alveolar macrophage - increased release in pulmonary inflammation and fibrosis. Neuropeptides 20:63 72, 1991.
  44. Khan MF, Kaphalia BS, Palafox A, Jerrells TR, Ansari GAS. Heated linoleic acid anilide:Toxicity and relevance to toxic oil syndrome. Toxicology 68:143 155, 1991.
  45. Khan MF, Gallagher JE, Brody AR. Effect of alveolar lining layer proteins and lipids on particle binding and phagocytosis. Toxicol In Vitro 4: 93 101, 1990.
  46. Khan MF, Abidi P, Anwer J, Ray PK, Anand M. Pulmonary biochemical assessment of fenitrothion toxicity in rats. Bull Environ Contam Toxicol 45: 598 603, 1990.
  47. Khan MF, Ali S, Rahman Q. Bioreactivity of intratracheally administered slate dust:Incorporation of 14C acetate into lung lipids.J Appl Toxicol 9: 305 311, 1989.
  48. Singh SV, Das B, Khan MF, Rahman Q. Interaction of silicate dusts with erythrocyte ghost membranes: In vitro studies. J Appl Toxicol 4: 236 240, 1984.
  49. Khan MF, Ali S, Singh SV, Rahman Q, Viswanathan PN. Pulmonary biochemical response to slate dust in rats. J Appl Toxicol 4: 87 91, 1984.
  50. Singh SV, Das B, Khan MF and Rahman Q. Binding of silicic acid to proteins from plasma and lung of rats: In vitro. Chem Biol Interactions 49: 155 164, 1984.
  51. Khan MF, Singh SV, Rahman Q. Alveolar macrophage and its role in the toxicity of particulate air pollutants. Biol Mem 9: 210 221, 1984.
  52. Khan MF, Jaffery FN, Ali S, Rahman Q. Biochemical studies on the toxicity of slate mine dust. Environ Health Perspect 51: 305 310, 1983.
  53. Singh SV, Das B, Khan, MF, Rahman Q. Binding of silicic acid from slate dust to human plasma protein component. Biol Mem 8: 165 171, 1983.
  54. Khan MF. Enhanced analgesic activity of liposomized met enkephalin analogue. Ind J Biochem Biophys 18: 440 441, 1981.

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