Premila Abraham

RESEARCH INTERESTS

1. Mechanism of anti -cancer drug induced organ toxicity and its prevention

• Methotrexate induced gastrointestinal toxicity

• Cyclophosphamide induced hemorrhagic cystitis

2.  Targeting endometrial cancer stem cells for the treatment of endometrial cancer using aspirin and curcumin

3.  Mechanism of hypoglycemic and hypolipidemic effects of mega doses of biotin in rat model of gestational diabetes

RESEARCH GRANTS

Projects submitted for funding

ICMR

1. Repurposing of aspirin for breast  cancer treatment ; Does it act  as anti -cancer stem cell agent by   targeting  COX dependent  / COX independent signalling pathways

CSIR

1. Mechanism of hypoglycemic and hypolipidemic effects of mega doses of biotin in rat model of gestational diabetes (Submitted August 2022)

2. A proteomic approach for the identification of mitochondrial nitrated proteins that may play a role in cyclophosphamide induced hemorrhagic cystitis and comparison of the efficacy of peroxynitrite scavengers (edaravone and ebselen ) with standard drug Mesna in the prevention of cyclophosphamide induced hemorrhagic cystitis in rats( Submitted August 2022)

DBT

1. Investigation of the role of Wnt-Trib2-AKT-GSK3β-Catenin Signaling Axis in Endometrial Cancer (EC) stemness; Effect of TRIB2 knockdown on stemness properties of EC cell lines and assessment of Trib2 as potential target for the treatment of endometrial cancer using cell lines and tumor xenograft model (Submitted Nov 2022)

Publications

(The names in bold indicate the authors from the Department of Biochemistry)

1. Sundari PN (Abraham P), Wilfred G, Ramakrishna. Does oxidative protein damage play a role in the pathogenesis of carbon tetrachloride-induced liver injury? Biochim.Biophys.Acta.1997;1362: 169- 76.

2. Abraham P, Wilfred G, Ramakrishna B. Effect of administration of the free radical trapping agent “N-tert-Butyl-Alpha-Phenylnitrone” on the prevention of oxidative damage to lipids and proteins of the liver and liver damage in experimental cirrhosis. Journal of Forensic Medicine and Toxicology1999; 16: 26-29.

3. Abraham P, Wilfred G, Ramakrishna B. Decreased activity of hepatic alkaline protease in rats with carbon tetrachloride-induced liver cirrhosis.Indian Journal of Experimental Biology 1999; 37: 1243-1245.

4. Abraham P, Wilfred G, Cathrine SP. Oxidative damage to the lipids and proteins of the lungs, testis and kidney of rats during carbon tetrachloride intoxication.ClinicaChimicaActa 1999; 289: 177-179

5. Abraham P, Wilfred G. Lysosomal enzymes in the pathogenesis of carbon tetrachloride induced injury to the kidney and testis in the rat. Indian Journal of Pharmacology 2000; 32: 250-251.

6. Abraham P, Wilfred G, Ramakrishna B. Plasma prolidase may be an index of liver fibrosis in the rat.ClinicaChimicaActa 2000; 295: 199-202.

7. Abraham P, Wilfred G. Oxidative damage to the lipids and proteins of the lungs of ratsupon acute exposure to carbon tetrachloride vapours. International Journal of Medical Toxicology and Legal Medicine 2001; 3: 22:16-17.

8. Abraham P, Wilfred G. A massive increase in serum β-glucuronidase after a single dose of carbon tetrachloride to the rat. ClinicaChimicaActa2002; 322: 183-184.

9. Abraham P, Wilfred G. Oxidative damage to the hepatocellular proteins after chronic ethanol intake in the rat.ClinicaChimicaActa2002; 325: 117-125.

10. Abraham P, Wilfred G. A marked decrease in the activity of biotinidase in the plasma of rats after single dose of carbon tetrachloride.ClinicaChimicaActa 2003;328:195- 97.

11. Abraham P, Wilfred G,Ramakrishna B. Decrease in plasma biotinidase activity with normal albumin concentrations in experimental liver fibrosis. ClinicaChimicaActa2003; 334: 245-247.

12. Abraham P. Lysosomal enzyme activity during development of carbon tetrachloride induced cirrhosis in rats. Indian J PhysiolPharmacol 2004; 48: 206-212.

13. Abraham P. Oxidative stress in paracetamol-induced pathogenesis:(I)renal damage. IndianJournal of Biochemistry and Biophysics 2004; 42: 59-62.

14. Abraham P. Increased protein thiol in the liver and plasma of rats in acute acetaminophen intoxication.ClinicaChimicaActa 2004; 339: 203-204.

15. Abraham P. Increased plasma biotinidase activity in rats with paracetamol induced acute liver injury. ClinicaChimicaActa2004 ;349:61-65

16. Abraham P. Megadose of vitamin C augments the nephrotoxicity of paracetamol. Nephrology 2005;10: 623-625. -1840.

17. Abraham P, Desigamani K and Indirani K. Nitro Arginine Methyl ester, a non selective inhibitor of nitric oxide synthase reduces ibuprofen induced gastric mucosal injury in the rat. Digestive Diseases Science 2005; 50: 1832

18. Abraham P, Indirani K, Bondu JD. Propylthiouracil attenuates acetaminophen induced renal damage in the rat. Nephrology 2005;10: 588-593.

19. Abraham P. Vitamin C may be beneficial in the prevention of paracetamol induced renal damage. Clinical and Experimental Nephrology 2005;9: 24-30.

20. Dhanarajan R, Abraham P,and Isaac B. Protective effect of ebselen, a selenoorganic drug , against gentamicin –induced renal damage in rats. Basic & Clinical Pharmacology & Toxicology 2006; 99:267.

21. Vyas R, Satishkumar S, Selvaraj KG, Suganthy J, Faith M, Isaac BandAbraham P. Teaching in Basic Sciences- A Novel approach integrated case based learning. The Alumini J of CMC, Vellore 2006; 40:11-15.

22. Sugumar E, Indirani K, Abraham P. Normal plasma creatininelevels despite histological evidence of renal damage in cyclophosphamide treated rats. ClinChimActa2007; 376: 244-245

23. Abraham P, Indirani K, Sugumar. E. Decrease in the activities of lysosomal enzymes may contribute to the urotoxicity of cyclophosphamide in the rat. Biomedical Research 2007; 18: 20-27.

24. Abraham P, Indirani K, Sugumar E. Effect of cyclophosphamide treatment on selected lysosomal enzymes in the kidney of rats. ExpToxicolPathol. 2007 Oct; 59(2):143-9.

25. Kolli VK, Abraham P, Isaac B. Alteration in antioxidant defense mechanisms in the small intestines of methotrexate treated rat may contribute to its gastrointestinal toxicity. Cancer therapy 2007; 5B: 501-510

26. Abraham P, Ramakrishna B. Oxidative stress plays a role in the pathogenesis of acetaminophen induced liver damage in the rat. Res and Rev in Biosciences 2007; 1:53-58.

27. Kolli VK, Abraham P, Rabi S Methotrexate-induced nitrosative stress may play a critical role in small intestinal damage in the rat.Arch Toxicol.2008 ; 82:763-70.

28. Abraham P, Sugumar E. Increased glutathione levels and activity of PON1 (phenyl acetate esterase) in the liver of rats after a single dose of cyclophosphamide: a defense mechanism?.ExpToxicolPathol. 2008 ; 59:301-6.

29. Abraham P, Sugumar E. Enhanced PON1 activity in the kidneys of cyclophosphamide treated rats may play a protective role as an antioxidant against cyclophosphamide induced oxidative stress.Arch Toxicol.2008 ; 82:237-8.

30. Abraham P,Kanakasabapathy I, Kulothungan P. Alterations in antioxidant enzyme activities and increased oxidative stress in cyclophosphamide induced hemorrhagic cystitis in the rat. Cancer therapy 2008; 6: 563-570.

31. Abraham P, Rabi S, Selvakumar D. Protective effect of aminoguanidine against oxidative stressand bladder injury in cyclophosphamide-induced hemorrhagic cystitis in rat. Cell BiochemFunct. 2009; 27:56-62.

32. Abraham P, Rabi S, Kulothungan P. Aminoguanidine, Selective Nitric Oxide Synthase Inhibitor, ameliorates Cyclophosphamide-induced Hemorrhagic Cystitis by Inhibiting Protein Nitration and PARS Activation. Urology 2009;73:1402-6.

33. Abraham P, Rabi S. Protein nitration, PARP activation and NAD+ depletion may play a critical role in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis in the rat.Cancer ChemotherPharmacol.2009 ; 64: 279-84.

34. Abraham P, Suganthy R. Nitrosative stress, protein tyrosine nitration, PARP activation and NAD depletion in the kidneys of rats after single dose of cyclophosphamide. Clinical and Experimental Nephrology 2009 ; 13:281-7

35. Abraham P, Kolli VK, Isaac B, Selvakumar D. Neutrophil infiltration and oxidative stress may play a critical role in methotrexate-induced renal damage. Chemotherapy 2009; 55: 83-90.

36. Abraham P, Kolli VK, Rabi S .Melatonin attenuates methotrexate-induced oxidative stress and renal damage in rats. Cell biochemistry and functions 2010 ; 28:426-33.

37. Abraham P, Isaac B. The effects of oral glutamine on cyclophosphamide-induced nephrotoxicity in rats. Hum ExpToxicol. 2011 ;30:616-23.

38. Abraham P, Isaac B, Ramamoorthy H, Natarajan K. Oral glutamine attenuates cyclophosphamide-induced oxidative stress in the bladder but does not prevent hemorrhagic cystitis in rats. J Medical Toxicology 2011 ;7:118-24

39. Abraham P, Isaac B. Ultrastructural changes in the rat kidney after single dose of cyclophosphamide-possible roles for peroxisome proliferation and lysosomal dysfunction in cyclophosphamide induced renal damage. Hum Exp Toxicol. 2011 Dec;30(12):1924-30.

40. Abraham P, Rabi S. Protective effect of aminoguanidine against cyclophosphamide induced oxidative stress and renal damage in rats. Redox report 2011;16: 6-12.

41. Abraham P, Rabi S. Aminoguanidine, a Selective Nitric Oxide Synthase Inhibitor, attenuates Cyclophosphamide-induced renal damage by Inhibiting Protein Nitration and PARP(S) Activation. Chemotherapy 2011;57: 327-334 .

42. Ramamoorthy H, Abraham P, Isaac B. Oxidative stress, decreased activities of anti-oxidant enzymes, and neutrophil infiltration contribute to Tenofovir disoproxil fumarate induced renal damagein rats. International Research of Pharmacy and Pharmacology 2011; 1(10) : 259-270, Special Issue.

43. Faith M, Abraham P. An update on diagnostic value of biotinidase: From liver damage to cancer : Minireview. Biomedical Research 2013; 24 (2): 195-201.

44. Kolli VK, Abraham P, Isaac B, Kasthuri N. Preclinical efficacy of melatonin to reduce methotrexate-induced oxidative stress and small intestinal damage in rats. Dig Dis Sci. 2013 Apr;58(4):959-69.

45. Kolli VK, Kanakasabapathy I, Faith M, Ramamoorthy H, Isaac B, Natarajan K, Abraham P. A preclinical study on the protective effect of melatonin against methotrexate-induced small intestinal damage: effect mediated by attenuation of nitrosative stress, protein tyrosine nitration, and PARP activation. Cancer Chemother Pharmacol. 2013 May;71(5):1209-18.

46. Abraham P, Ramamoorthy H, Isaac B.Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney .J Biomed Sci. 2013 Aug 19;20:61.

47. Kolli V, Natarajan K, Isaac B, Selvakumar D, Abraham P. Mitochondrial dysfunction and respiratory chain defects in a rodent model of methotrexate-induced enteritis. Hum Exp Toxicol. 2014 Dec 17, 2013. [Epub ahead of print]

48. Ramamoorthy H, Abraham P, Isaac B. Mitochondrial dysfunction and electron transport chain complex defect in a rat model of tenofovir disoproxil fumarate nephrotoxicity. J Biochem Mol Toxicol. 2014; 28(6):246-55.

49. Kolli V, Natarajan K, Isaac B, Selvakumar D, Abraham P. Mitochondrial dysfunction and respiratory chain defects in a rodent model of methotrexate-induced enteritis. Hum Exp Toxicol. 2014;33(6): 1055-61.

50. Ramamoorthy H, Abraham P, Isaac B. Preclinical efficacy of melatonin in the amelioration of tenofovir nephrotoxicity by the attenuation of oxidative stress, nitrosative stress, and inflammation in rats. J Basic Clin Physiol Pharmacol. 2014; 27:1-13.

51. Ramamoorthy H, Isaac B, Abraham P. Tenofovir induced renal damage is associated with activation of NF-κB inflammatory signaling pathway and PARP overactivation. BMC Infectious Diseases. 2014;14 (Suppl 3):E5.

52. Abraham P, Hemalatha R, Isaac B. A reliable and reproducible rodent model of Tenofovir disoproxil fumarate (TDF) (anti-HIV drug) nephrotoxicity that resembles human TDF tubulopathy. Biomedical research 2015: 27 (1): 974-982.

53. Natarajan K, Abraham P. Methotrexate administration induces differential and selective protein tyrosine nitration and cysteine nitrosylation in the subcellular organelles of the small intestinal mucosa of rats. Chemico-biological interactions 2016; 251(5):45-59.

54. Abraham P, Isaac B, Imbalance Between Peroxisomal ROS Generating Enzymes and ROS Scavenging Enzymes May Contribute to Cyclophosphamide Induced Renal Damage in Rats. Indian Journal of Applied Research 2016:6(11): 72-77.

55. Abraham P, Rabi S, Francis DV, D Mohana Priya, Natarajan K, A. Amaladass. Increased hepatic gluconeogenesis and decreased glucose uptake, and increased hepatic de novo lipogenesis in rat model of maternal diabetes. Biomedical Research 2016; 27 (2): 621-629.

56. Ramamoorthy H, Abraham P, Isaac B, Selvakumar D. Role for NF-κB inflammatory signalling pathway in tenofovir disoproxil fumarate (TDF) induced renal damage in rats. Food Chem Toxicol. 2017 Jan; 99:103-118.

57. Natarajan K, Abraham P, Kota R, Selvakumar D.Aminoguanidine pretreatment prevents methotrexate-induced small intestinal injury in the rat by attenuating nitrosative stress and restoring the activities of vital mitochondrial enzymes. J Basic Clin Physiol Pharmacol. 2017 Jan 18. pii: /j/jbcpp.ahead-of-print/jbcpp-2016-0099/jbcpp-2016-0099.xml.

58. Natarajan K, Abraham P, Kota R. Activation of the mitochondrial apoptotic pathway contributes to methotrexate-induced small intestinal injury in rats. Cell Biochem Funct. 2017 Oct;35(7):378-391. doi: 10.1002/cbf.3285. Epub 2017 Sep 4.

59. Abraham P, Hemalatha R, Francis DV, Suganthy R.Beneficial Effects of Megadoses of Biotin in Streptozotocin-induced Gestational Diabetes Mellitus in Rats – A Preliminary Study. Indian J Physiol Pharmacol 2017; 61(2) :159-165.

60. Natarajan K, Abraham P, Kota R, Isaac B.NF-κB-iNOS-COX2-TNF α inflammatory signaling pathway plays an important role in methotrexate induced small intestinal injury in rats. Food Chem Toxicol. 2018 ;118:766-783.

61.  Rammamoorthy H, Abraham P. Mitochondrial pathway of apoptosis and necrosis contribute to tenofovir disoproxil fumarate -induced renal damage in rats. Human and experimental toxicology . 2018 Oct 16:960327118802619. doi: 10.1177/0960327118802619.

62. Hemalatha R, Abraham P, Isaac B, Selvakumar D. Mitochondrial pathway of apoptosis and necrosis contribute to tenofovir disoproxil fumarate -induced renal damage in rats. Hum Exp Toxicol. 2019 Mar;38(3):288-302 

63. Ramamoorthy H, Abraham P, Isaac B Melatonin protects against tenofovir-induced nephrotoxicity in rats by targeting multiple cellular pathways. Human and experimental toxicology 2021 May;40(5):826-850 Impact factor, JCR- 2.903). 

64. Muthuraman N, Vijayselvi R, Sudhakar P Y, Christudoss P, Abraham P Assessment of serum biotin levels and its association with blood glucose in gestational diabetes mellitus.  Eur J Obstet Gynecol Reprod Biol X. 2023;17:100181.

65. Hemalatha R, Muthuraman N, Sandya Rani B, Abraham P. A study on the alteration of endoplasmic reticulum stress related proteins in cyclophosphamide induced damage to urothelium.  Pharm Biomed Res 2023; 9 (2) :153-162

CHAPTERS IN BOOKS

1. Premila Abraham, Bina Isaac. Protective Effects of Exogenous Melatonin Against Methotrexate-Induced Intestinal Injury October 2014DOI10.1007/978-81-322-0825-9_29In book: Melatonin and Melatonergic Drugs in Clinical Practice Melatonin and Melatonergic Drugs in Clinical Practice chapter 29; pp 389-402. 

AWARDS

1. PMSDS (Pharma Medical Sciences Development Society) Excellence in Research Award 2021 for outstanding contribution in the field of Medical Biochemistry

2. DBT National Women Scientist award 2010

3. DBT Crest International fellowship Award 2011

4. ICMR – Shakuntala Amirchand prize award 2005

5. The Tamil Nadu Young Womens’ scientist award 2004