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ORIGINAL ARTICLE
Year : 2014  |  Volume : 17  |  Issue : 3  |  Page : 343-345

Effects of N-acetyl cysteine on lipid levels and on leukocyte and platelet count in rats after splenectomy


1 Department of General Surgery, Medical Faculty, Abant Izzet Baysal University Hospital, Bolu, Turkey
2 Department of Biochemistry, Abant Izzet Baysal University Hospital, Bolu, Turkey
3 Department of Internal Medicine, Abant Izzet Baysal University Hospital, Bolu, Turkey

Date of Acceptance03-Oct-2013
Date of Web Publication9-Apr-2014

Correspondence Address:
M Sit
Department of General Surgery, Medical Faculty, Abant Izzet Baysal University, Bolu
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1119-3077.130237

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   Abstract 

Introduction: Many of studies have shown that increased lipid levels play a significant role in the pathogenesis of atherosclerosis after splenectomy. We investigated the effects of N-acetyl cysteine (NAC) on lipid parameters and leukocyte and platelet (PLT) levels following splenectomy.
Materials and Methods: 32 Sprague-Dawley rats weighing from 200 to 250 g were placed into four experimental groups. For 42 days post-operatively, all rats were fed standard rat food and water and the rats in the first group ( n = 8) received no intraperitoneal infusion. Rats in the second group ( n = 6) were given a 50 mg/kg saline solution (SF); those in the third group ( n = 8) received 50 mg/kg NAC and the rats in the fourth group ( n = 8) were administered a 100 mg/kg NAC infusion intraperitoneally.
Results: All parameters other than white blood cell count were significantly different between the four groups. There were no significant differences between the control and SF groups in terms of total cholesterol and PLT levels. Triglyceride (TG), very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) levels were significantly elevated in the SF group compared with the control rats. There was no statistically significant difference between the SF and NAC 50/100 groups in terms of low-density lipoprotein levels. Total cholesterol, TG, HDL and VLDL levels were significantly reduced and the PLT level was significantly elevated in the NAC 50 and NAC 100 groups compared with the SF group.
Conclusion: Serum VLDL and TG levels should be monitored in patients after splenectomy. For reduction in these lipid parameters, early NAC treatment should be initiated. More prospective larger studies are needed to confirm our results.

Keywords: High-density lipoprotein, low-density lipoprotein, N-acetyl cysteine, splenectomy, triglyceride


How to cite this article:
Sit M, Yilmaz E E, Tosun M, Aktas G. Effects of N-acetyl cysteine on lipid levels and on leukocyte and platelet count in rats after splenectomy. Niger J Clin Pract 2014;17:343-5

How to cite this URL:
Sit M, Yilmaz E E, Tosun M, Aktas G. Effects of N-acetyl cysteine on lipid levels and on leukocyte and platelet count in rats after splenectomy. Niger J Clin Pract [serial online] 2014 [cited 2019 Nov 14];17:343-5. Available from: http://www.njcponline.com/text.asp?2014/17/3/343/130237


   Introduction Top


Many of the studies have shown that increased lipid levels play a significant role in the pathogenesis of atherosclerosis after splenectomy due to trauma, cysts and hypersplenism. Numerous animal studies have indicated that lipid and platelet (PLT) parameters could be restored after splenectomy if splenic autotransplantation were performed. [1],[2]

N-acetyl cysteine (NAC) is a hydrophilic glutathione predecessor. Increased glutathione levels provide a decrease in tissue damage and a reduction in oxidative damage and lipid peroxidation. [3] NAC increases high-density lipoprotein (HDL) cholesterol levels, but has no effect on other lipid-lipoprotein parameters. [4] Leukocytosis and thrombocytosis often occur after splenectomy. [5],[6]

We aimed to investigate the effects of NAC on lipid parameters and leukocyte and PLT levels following splenectomy. We also observed whether impaired lipid parameters improved after splenectomy with NAC treatment. Furthermore, we investigated white blood cell (WBC) and PLT levels in the post splenectomy period after the application of NAC.


   Materials and Methods Top


32 Sprague-Dawley rats weighing about 200-250 g were grouped into four experimental groups. They had been fasting for 12 h before surgery. All surgical interventions were performed in sterile rooms and under anaesthesia with 40 mg/kg ketamine and 5 mg/kg xylasine. The abdominal skin was shaved and sterilized with a povidine iodine solution. Splenectomy was performed for all rats on the same day by the same surgical staff.

For 42 days post-operatively, all rats were fed with standard rat food and water and the rats in the first group (n = 8) received no intraperitoneal infusion. Rats in the second group (n = 6) were given a 50 mg/kg SF, while rats in the third group (n = 8) received 50 mg/kg NAC. The rats in the fourth group (n = 8) were administered a 100 mg/kg NAC infusion intraperitoneally.

At the end of the experimental protocol, a total volume of 3 ml blood samples were obtained from the intracardiac space from all rats under anaesthesia. The centrifuged plasma was stored at −80 ° C until the biochemical evaluation. Malondialdehyde, lipid peroxidase, glutathione peroxidase, myeloperoxidase, low-density lipoprotein (LDL), oxide LDL, very-low-density lipoprotein (VLDL), triglyceride (TG), HDL, total cholesterol and hemogram parameters were assessed from the blood and plasma samples.

Statistical analyses

The statistical package for the social sciences (SPSS) software (version 17 for Windows; SPSS Inc., Chicago, IL, US) was used to analyse the data. The Shapiro-Wilk test was used to detect whether the distributions of continuous variables were normal. Homogeneity of variances was evaluated with the Levene test. Data are shown as means ± standard deviations or medians (interquartile range), where appropriate. One-way analysis of variance (ANOVA) was performed to compare the mean differences between groups. Otherwise, the Kruskal-Wallis test was used for comparisons of median values. When the P values from the one-way ANOVA or Kruskal-Wallis test statistics were statistically significant, a post hoc Tukey honestly significant difference or Conover's non-parametric multiple comparison tests was used to determine which groups differed from the others. P < 0.05 was considered to indicate statistical significance. To control type I errors, the Bonferroni adjustment was performed for all multiple comparisons.


   Results Top


All parameters other than WBC count were significantly different between the four groups. There were no significant differences between the control and SF groups in terms of total cholesterol and PLT levels. TG, VLDL, and HDL levels were significantly elevated in the SF group compared with the control rats. However, LDL levels were significantly reduced in the SF group compared with the control group. There was no statistically significant difference between control rats and the NAC 50 group in terms of TG and VLDL levels. Total cholesterol, HDL and LDL levels were significantly reduced in the NAC 50 group compared to the control group. However, PLT levels were significantly elevated in this group compared to the control rats, while VLDL and HDL levels were not significantly different between the NAC 100 group and the control rats. Total cholesterol and LDL levels were significantly reduced and TG and PLT levels were significantly elevated in the NAC 100 group when compared to the control group.

There was no statistically significant difference between the SF and NAC 50/100 groups in terms of LDL levels. Total cholesterol, TG, HDL, and VLDL levels were significantly reduced, and the PLT count was significantly elevated in the NAC 50 and NAC 100 groups compared to the SF group. There was no significant difference between the NAC 50 and the NAC 100 groups.

[Table 1] shows a comparison of the laboratory parameters of the groups and [Table 2] presents the differences of the parameters between groups.
Table 1: Comparison of the laboratory parameters of the groups


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Table 2: Differences of the parameters between groups


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   Discussion Top


We found that LDL was reduced and the PLT count was increased after splenectomy. HDL levels were elevated following splenectomy but reduced after NAC treatment. The PLT count did not change after splenectomy in rats that received SF. In contrast, the PLT counts of the rats that were given NAC (both 50 and 100 mg) were elevated. Total cholesterol levels were reduced after splenectomy in the groups that received NAC (both 50 and 100 mg). TG levels were elevated after splenectomy in the SF and NAC 100 groups.

An elevation in PLT count is very common after splenectomy. [7] Our results were similar to those found in the literature. NAC treatment did not reverse the elevation in PLT count following splenectomy. Fatouros et al. reported an increase in TG and a decrease in HDL levels after splenectomy. [8] Similarly, we found that TG levels were elevated after splenectomy, but were reduced after NAC treatment. Therefore, the TG elevation seen in patients who have undergone splenectomy should be treated with NAC.

NAC has been reported to increase HDL levels. [9] In contrast, we found that NAC reduced elevated HDL levels following splenectomy. Fatouros et al. report had similar findings to our results. [8] These results are confusing; why did NAC reduce both TG and HDL levels?

Elevated VLDL levels after splenectomy were reduced by NAC in the present study. However, we could not found a similar association for LDL levels. The splenectomy procedure itself caused a decrease in LDL levels. NAC treatment did not produce a further decrease or increase. Aviram et al. reported that splenectomy caused an elevation in LDL levels. [10] Another report in literature suggested Aviram et al.'s results. [11]

Increased splenic function and splenomegaly may act in opposition to the splenectomy condition. A previous study pointed out that TG, total cholesterol and LDL levels were elevated in patients with splenomegaly compared to controls without splenomegaly. [12] However, splenectomy should have the opposite effect. In our study, although LDL levels were reduced after splenectomy, TG, HDL and VLDL levels all increased after splenectomy. The spleen may be a storage reservoir for TG, HDL and VLDL; therefore, splenectomy may cause an elevation in their serum concentrations.


   Conclusion Top


Serum VLDL and TG levels should be monitored in patients after splenectomy. For reduction in these lipid parameters, early NAC treatment should be initiated. More prospective larger studies are needed to confirm our results.

 
   References Top

1.Petroianu A, Veloso DF, Alberti LR, de Souza Vasconcellos L. Plasma lipid alterations after total splenectomy, subtotal splenectomy and splenic auto-implants in rats. J Gastroenterol Hepatol 2008;23:e221-4.  Back to cited text no. 1
    
2.Akan AA, Sengül N, Simºek S, Demirer S. The effects of splenectomy and splenic autotransplantation on plasma lipid levels. J Invest Surg 2008;21:369-72.  Back to cited text no. 2
    
3.Eskiocak S, Altaner S, Bayir S, Cakir E. The effect of N-acetylcysteine on brain tissue of rats fed with high-cholesterol diet. Turk J Biochem 2008;33:58-63.  Back to cited text no. 3
    
4.Franceschini G, Werba JP, Safa O, Gikalov I, Sirtori CR. Dose-related increase of HDL-cholesterol levels after N-acetylcysteine in man. Pharmacol Res 1993;28:213-8.  Back to cited text no. 4
    
5.Pisters PW, Pachter HL. Autologous splenic transplantation for splenic trauma. Ann Surg 1994;219:225-35.  Back to cited text no. 5
    
6.Toutouzas KG, Velmahos GC, Kaminski A, Chan L, Demetriades D. Leukocytosis after posttraumatic splenectomy: A physiologic event or sign of sepsis? Arch Surg 2002;137:924-8.  Back to cited text no. 6
    
7.Boxer MA, Braun J, Ellman L. Thromboembolic risk of postsplenectomy thrombocytosis. Arch Surg 1978;113:808-9.  Back to cited text no. 7
[PUBMED]    
8.Fatouros M, Bourantas K, Bairaktari E, Elisaf M, Tsolas O, Cassioumis D. Role of the spleen in lipid metabolism. Br J Surg 1995;82:1675-7.  Back to cited text no. 8
    
9.Kinscherf R, Cafaltzis K, Röder F, Hildebrandt W, Edler L, Deigner HP, et al. Cholesterol levels linked to abnormal plasma thiol concentrations and thiol/disulfide redox status in hyperlipidemic subjects. Free Radic Biol Med 2003;35:1286-92.  Back to cited text no. 9
    
10.Aviram M, Brook JG, Tatarsky I, Levy Y, Carter A. Increased low-density lipoprotein levels after splenectomy: A role for the spleen in cholesterol metabolism in myeloproliferative disorders. Am J Med Sci 1986;291:25-8.  Back to cited text no. 10
[PUBMED]    
11.Gilbert HS, Ginsberg H, Fagerstrom R, Brown WV. Characterization of hypocholesterolemia in myeloproliferative disease. Relation to disease manifestations and activity. Am J Med 1981;71:595-602.  Back to cited text no. 11
[PUBMED]    
12.Wysocki A, Drozdz W, Dolecki M. Splenomegaly and plasma lipids. Przegl Lek 1998;55:365-7.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2]


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