PLASMA LIPID ALTERATIONS IN LEUKEMIA PATIENTS
M. Imran Qadir1, M. Saleem1, Syed Haroon Khalid2, Salman Akbar Malik3, Asif Massud1, Mohsin Ali1, Sajid Asghar1 and M. Sajid Hamid Akash1
1. College of Pharmacy, GC University, Faisalabad, Pakistan 2. School of Pharmaceutical Sciences, University Sains Malaysia, Pulau Pinang, Malaysia 3. Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan
Keywords: Cancers, Leukemia, Plasma lipid profile, Triglycerides, Cholesterol, LDL-Cholesterol and HDL-Cholesterol
Abstract

Neoplastic disease indicates a disease of new growth. Neoplasms or tumors may be divided into two categories; benign tumors and malignant tumors. Benign tumors are relatively innocent and remain localized. Malignant tumors are also called cancers and are distinguished from benign tumors by the properties of invasiveness and metastasis. Cancer of the leukocytes and their precursors is known as leukemia. Triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol constitute plasma lipid profile. Objective of the present study was to investigate relationship of plasma lipid profile (Triglycerides, Cholesterol, LDL-Cholesterol and HDL-Cholesterol) with leukemia. 180 subjects were included in the study. The subjects comprised of two groups; first as Controls (90 in number) and the second as Patients of Leukemia (also 90 in number). Fasting blood samples were collected for estimation of plasma lipid levels. Comparison between mean values of plasma lipid profile of control subjects and leukemia patients indicated that there was moderate decrease in all plasma levels of leukemia patients: triglycerides (31.29%, P < 0.01), cholesterol (27.15%, P < 0.01), LDL-cholesterol (23.28%, P < 0.01) and HDL-cholesterol (24.70%, P<0.05). As there is a change in plasma lipid profile of leukemia patients, the plasma lipid profile may be used as adjuvant for identification of the disease along with the standard diagnostics tools.

Article Information

Identifiers and Pagination:
Year:2011
Volume:3
First Page:45
Last Page:50
Publisher Id:JAppPharm (2011 ). 3. 45-50
Article History:
Received:September 11, 2010
Accepted:January 7, 2011
Collection year:2010
First Published:January 11, 2011

INTRODUCTION

Neoplastic disease indicates a disease of new growth. Fundamental to the origin of all neoplasms is loss of normal growth control. Neoplasms seem to behave as parasites and compete with normal cells and tissues for their metabolic need. A neoplasm is often referred to as a tumor. All tumors have two basic components: the parenchyma; made up of neoplastic cells, and the stroma; made up of non-neoplastic connective tissues and blood vessels.

Neoplasms or tumors may be divided into two categories; benign tumors and malignant tumors. Benign tumors are relatively innocent and remain localized. Malignant tumors are also called cancers and are distinguished from benign tumors by the properties of invasiveness and metastasis. Malignant tumors can be further classified into four major classes:  carcinomas, sarcomas, lymphomas and leukemias. Cancers of epithelial cells are known as carcinomas, cancers of connective tissues are known as sarcomas, cancers of lymphoid tissues are known as lymphomas and the cancers of the leukocytes and their precursors is known as leukemias [1].

  Lipids are heterogeneous group of compounds that provide energy to the body. Cholesterol and triglycerides, important lipid constituents of cell, are essential to carry out several vital physiological functions. Cholesterol is essential for maintenance of the structural and functional integrity of all biological membranes. Lipids are relatively insoluble in water. Thus they are carried in body fluids as soluble protein complexes known as lipoproteins. Low density lipoproteins (LDL) are responsible for the transport of cholesterol from liver to the cells and high density lipoproteins (HDL) are involved for the transport of cholesterol from cells to the liver [2, 3]. Triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol constitute plasma lipid profile [4, 5]. Workers have tried to investigate an association of plasma/serum lipids and lipoproteins with different cancers [6-9].

The objective of the present study was to investigate any relationship between plasma lipid profile (Triglycerides, Cholesterol, LDL-Cholesterol and HDL-Cholesterol) and leukemia.

 

MATERIALS AND METHODS

STUDY DESIGN               

A prospective study was carried out in 180 individuals. Out of them 90 were control subjects, 45 males and 45 females; who had no complaint or any major illness in recent past. They were close relatives of the patients accompanying them during their hospitalization.  The remaining 90 were patients of leukemia.

Selection Criteria: Only those patients were selected for the study that do not had a history of thyroid disease, diabetes or other major illness that could affect lipid metabolism. These patients were not treated with any chemotherapy, radiation or surgery before the sample collection.

Sample Collection: Blood samples were collected from Combined Military Hospital, Rawalpindi, Pakistan and NORI Hospital, Islamabad, Pakistan. The patients were fasted overnight before the sample collection. The plasma was stored at -20 oC and levels of plasma lipids were estimated within the 48 hours of sample collection.

ESTIMATION OF PLASMA LIPID PROFILE

Plasma levels of triglycerides, total cholesterol, LDL-cholesterol and HDL-cholesterol were estimated by using spectrophotometer. The method was used by Qadir et al. (2006, 2007, 2008) for estimation of plasma lipids [7-9].

TRIGLYCERIDES:

                Triglycerides were determined by enzymatic method (GPO-PAP Method), using the commercially available kit manufactured by Human, Germany.

Procedure

Three Cuvettes were washed with distilled water and were labeled Blank, standard and sample. 20 ?l distilled water, 20 ?l standard and 20 ?l sample, was pipetted in each cuvette respectively. Chromogen reagent, 2 ml was added to each cuvette. Contents of all the cuvettes were mixed thoroughly and incubated for 5 minutes at room temperature. The wavelength of spectrophotometer was set at 500 nm. Result command was given to spectrophotometer and after some time results were displayed. The blood triglycerides levels were calculated by applying the following formula.

                                               

                                                                                      Absorbance of sample

                    Triglycerides mg/dl      =                                                                  x  200

                                                                                    Absorbance of standard

TOTAL CHOLESTEROL:

Rapid enzymatic determination of the total cholesterol by CHOD-PAP method (10), was performed by using the commercially available kit manufactured by Human, Germany.

Procedure

Three Cuvettes were washed with distilled water and were labeled blank, standard and sample. 20 ?l distilled water, 20 ?l standard and 20 ?l sample was pipetted in each cuvette respectively. Chromogen reagent, 2 ml was added to each cuvette. Contents of all the cuvettes were mixed thoroughly and incubated for 5 minutes at 37°C. The wavelength of spectrophotometer was set at 500 nm. Result command was given to spectrophotometer and after some time results were displayed. The blood cholesterol levels were calculated by applying the following formula.

 

                                                                                 Absorbance of sample

     Cholesterol mg/dl      =      ——————————    x   200                                                     

                                                                Absorbance of standard

LDL-CHOLESTEROL:

LDL-cholesterol was determined by precipitation method. Tests were performed by using the commercially available kit manufactured by Randox, Germany.

Procedure

For sample preparation; 100 ?l sample and 1000 ?l precipitant were placed in a tube. After through mixing the tube was allowed to stand for 15 minutes at room temperature and then was centrifuged at 1500 rpm for 15 minute. Supernatant was separated from the sediment and cholesterol was measured by the CHOD-PAP method. The LDL-cholesterol levels were calculated by applying the following formula.

LDL-cholesterol mg/dl = Total cholesterol – Cholesterol in supernatant.

HDL-CHOLESTEROL:

HDL-cholesterol was determined by using the commercially available kit manufactured by Randox, Germany.

Procedure

For sample preparation; 200 ?l sample and 500 ?l precipitant were placed in a tube. After through mixing the tube was allowed to stand for 10 minutes at room temperature and then was centrifuged at 4000 rpm for 10 minute. Supernatant was separated from the sediment and cholesterol was measured by the CHOD-PAP method.

STATISTICAL ANALYSIS

Computer program SPSS 11.0 version was used for statistical analyses. Student t-test was performed to compare mean values of the parameters. “P” value < 0.05 was considered to be statistically significant.

RESULTS

In the present study, plasma level of Triglycerides in control males was between 130-138 mg/dl with a mean value of 144.27±4.21. Plasma level of Cholesterol in control males was between 133-213 mg/dl with a mean value of 173.42±9.34. Plasma level of LDL-Cholesterol in control males was between 58-89 mg/dl with a mean value of 70.47±8.82. Plasma level of HDL-Cholesterol in control males was between 34-66 mg/dl with a mean value of 48.90±7.54.       

                Plasma level of Triglycerides in control females was between 125-179 mg/dl with a mean value of 152.18±7.06. Plasma level of Cholesterol in control females was between 135-205 mg/dl with a mean value of 170.93±8.47. Plasma level of LDL-Cholesterol in control females was between 52-95 mg/dl with a mean value of 72.16±10.05. Plasma level of HDL-Cholesterol in control females was between 40-71 mg/dl with a mean value of 50.30±5.23.

Comparison  between  mean  values of  plasma  lipid  profile of  control  males and  control  females  showed  statistically  no  significant  difference. Thus mean of the two were taken as reference values. The reference value for triglycerides is 148.22±5.64 mg/dl, for cholesterol is 172.18±8.90 mg/dl, for LDL-cholesterol is 71.32±9.44 mg/dl and for HDL-cholesterol is 49.60±6.38 mg/dl.

In leukemia patients, plasma level of Triglycerides was between 64-155 mg/dl with a mean value of 101.83±5.33. Plasma level of Cholesterol was between 89-147 mg/dl with a mean value of 125.44±9.12. Plasma level of LDL-Cholesterol was between 36-66 mg/dl with a mean value of 54.71±7.21. Plasma level of HDL-Cholesterol was between 27-48 mg/dl with a mean value of 37.35±3.25

Comparison between mean values of plasma lipid profile of control subjects and Leukemia patients is given in Table 1. There is moderate decrease in all plasma levels of Leukemia patients: triglycerides (31.29%, P < 0.01), cholesterol (27.15%, P < 0.01), LDL-cholesterol (23.28%, P < 0.01) and HDL-cholesterol (24.70%, P<0.05).

 

Table1: Plasma Lipid Profile of Control Subjects & Patients of Leukemia (Mean ± SD)

 

Triglycerides

(mg/dl)

Cholesterol

(mg/dl)

LDL-Cholesterol

(mg/dl)

HDL-Cholesterol

(mg/dl)

Control Subjects

148.22±5.64

172.18±8.90

71.32±9.44

49.60±6.38

Leukemia Patients

101.83±5.33*

125.44±9.12*

54.71±7.21*

37.35±3.25**

* P < 0.01 as compared to control

** P<0.05 as compared to control

 

Graphical representation of comparison between mean values of plasma lipid profile of control subjects and leukemia patients is given in figure 1.

 

Figure 1: Comparison between plasma lipid profile of control subjects and leukemia patients

 

DISCUSSION

                Several studies of plasma lipid alterations in animals with neoplasm have been conducted [11, 12]. The first correlation between plasma lipids and human malignancy was reported in women with breast cancer [13, 14]. The return of plasma lipids and lipoproteins towards normal limits during remission confirms the correlation of lipid alterations with primary disease activity [15, 16].

The results of our study suggest that all the plasma lipid components (triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol) of leukemia patients showed significant decrease, when compared with the normal control subjects. P<0.01 for triglycerides, cholesterol and LDL-cholesterol; and P<0.05 for HDL-cholesterol were observed. These results are also in agreement with the reports of Musolino et al., 2002 [17].

The patho-physiologic mechanism implicated in plasma lipid alterations during neoplasm has not been determined. Lipids are major cell membrane components essential for various biological functions including cell growth and division of normal and malignant tissues. Low levels of cholesterol in the proliferating tissues and in blood compartments could be due to the process of carcinogenesis.

CONCLUSION

This study has shown that plasma lipid levels are decreased in leukemia patients. As there is a change in plasma lipid profile of leukemia patients, the plasma lipid profile may be used as adjuvant for identification of the disease along with the standard diagnostics tools.

 

REFERENCES

1.       Robbins, S.L.; Cotran, R.S.; Kumar V. (2003) Neoplasia, In: Robbins Basic Pathology, 7th ed., Saunders, Philadelphia, USA, pp. 165-210. 

2.       Edwards, C.R.W.; Baired, J.D.; Frier, B.M.; Shephered, J.; Toft, A.D. (1995) Ischaemic heart disease. In: Davidsons Principles and Practice of Medicine edited by Edwards CRW, Boucher JAD, Haslett C and Chilvers E, 17th ed., ELBS, Churchill Livingstone: London, UK, pp 245-66.

3.       Fischbach, F.T. (1984) Chemistry Studies. In: A Manual of Laboratory Diagnostic Tests, 2nd ed., J. B. Lippincott Company: Philadelphia, USA. pp 223-358.

4.       Heeren, J.; Grewal, T.; Laatsch, A.; Rottke, D.; Rinninger, F. (2003) Recycling of apoprotein E is associated with cholesterol efflux and HDL internalization. J. Bio. Chem., 278 (16), 14370-78

5.       Murray, R.K.; Granner, D.K.; Mayes, P.A.; Rodwell, V.W. (2000) Lipid transport and storage, Appendix. In:  Harper’s Biochemistry, 25th ed., Appleton & Lange: USA. pp 268-84 and 867-72.

6.       Patel, P.S.; Shah, M.H.; Jha, F.P.; Raval, G.N.; Rawal, R.M.; Patel, M.M.; Patel, J.B.; Patel, D.D. (2004) Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions. Indian J. Canc., 41 (1), 25-31.

  1. Qadir, M.I.; Malik, S.A.; Naveed, A.K.; Ahmad, I. (2006) Plasma lipid profile in sarcoma patients. Pak. J. Pharm. Sci., 19 (2), 155-158.
  2. Qadir, M.I.; Naveed, A.K.; Ahmad, I.; Malik, S.A. (2007) Plasma lipid profile in childhood non-Hodgkin lymphoma patients. Pak. Paed. J., 31(4), 167-70.
  3. Qadir, M.I.; Malik, S.A. (2008) Plasma Lipid Profile in Gynecologic Cancers. Europ. J. Gynecol. Oncol. 29, 158-161.

10.    Allian, C.C.; Poon, L.S.; Chan, C.S.; Richmond, W. (1974) CHOD-PAP method for determination of total cholesterol. Clin. Chem., 20, 470.

11.    Cucuianu, A.; Malide, D.; Petrov, L. (1992) Serum cholesterol, apoprotein B and serum cholesterase activity in selected hematologic malignancies. Res Roum Med Int., 30, 261-268.

12.    Avall-Lundqvist, E.H.; Petersom, C.O. (1996) Serum cholesterol and apolipoprotein B levels may reflect disease activity in ovarian cancer patients. Acta. Oncol., 35, 1007-1010.

13.    Nonogaki, K.; Pan, X.M.; Moser, A.H. (1996) LIF and CNTF, which share the gp 130 transduction system, stimulate hepatic metabolism in rats. Am. J. Physiol., 271, 521-528.

14.    Kritchevsky, S.B.; Kritchevsky, D. (1992) Serum cholesterol and cancer risk: and epidemiologic prospective. Annu. Rev. Nutr., 12, 391-416.

15.    Baroni, S.; Scribano, D.; Zubbi, C. (1996) Prognostic relevance of lipoprotein cholesterol levels in acute lymphcytic and non-lymphocytic leukemia. Acta Haematol., 96, 24-28.

16.    Baroni, S.; Scribano, D.; Pagano, L. (1994) Lipids and lipoproteins in acute lymphoblastic leukemia. Leuk. Res., 18, 643-644.

17.    Musolino, C.; Calabro, L.; Bellomo, G.; Cincotta, M.; Di-Giacomo, V.; Pezzano, C.; Loteta, B.; Rizzo, V.; Guglielmo, S.; Alonci, A. (2002) Lipid profile in hematologic neoplasms. Recenti. Prog. Med. 93 (5), 298-301.


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Welcome to the research group of Prof. Dr. Cornelia M. Keck in Marburg. Cornelia M. Keck is a pharmacist and obtained her PhD in 2006 from the Freie Universität (FU) in Berlin. In 2009 she was appointed as Adjunct Professor for Pharmaceutical and Nutritional Nanotechnology at the University Putra Malaysia (UPM) and in 2011 she obtained her Venia legendi (Habilitation) at the Freie Universität Berlin and was appointed as a Professor for Pharmacology and Pharmaceutics at the University of Applied Sciences Kaiserslautern. Since 2016 she is Professor of Pharmaceutics and Biopharmaceutics at the Philipps-Universität Marburg. Her field of research is the development and characterization of innovative nanocarriers for improved delivery of poorly soluble actives for healthcare and cosmetics. Prof. Keck is executive board member of the German Association of Nanotechnology (Deutscher Verband Nanotechnologie), Vize-chairman of the unit „Dermocosmetics“ at the German Society of Dermopharmacy, active member in many pharmaceutical societies and member of the BfR Committee for Cosmetics at the Federal Institute for Risk Assessment (BfR).

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