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Effects of single dose administered nandrolone decanoate on serum cytokine levels and some biochemical parameters in male and female rats

Erdal Tasgin1*, Sefa Lök1, Seyfullah Haliloğlu3, Nagehan Demir2 and Hale Ergin3

1Selcuk University, School of Physical Education and Sport, 42075, Konya, Turkey

2Veterinary Doctor 42075, Konya, Turkey

3Department of Biochemistry, Veterinary Faculty, Selcuk University, 42075 Konya, Turkey

*Corresponding Author:
Erdal Tasgin
Selcuk University
School of Physical Education and Sport, Turkey

Accepted date: January 24, 2017

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Abstract

The aim this this study was to determine that administration of single higher dose nandrolone decanoate (40 mg/kg) on serum IL-1β, TNF-α, IL-10 and IL-6 levels and some biochemical parameters during 24 h in male and female rats. The blood samples were taken from 5 male and female rats to obtain their starting values. Then the blood samples were taken from 6 rats in sampling time at 1st, 2nd, 4th, 8th, 12th and 24th h following the nandrolone decanoate administration. There were significant increases determined in the serum IL-1β levels, numerical increases in the TNF-α levels whereas decreased IL-6 levels were determined. IL-10 levels did not change during experimental period. While serum GGT and BUN levels increased towards the last h of the study, increased ALP levels were observed only female rats. There was no any significance changes were determined in the other biochemical (ALT, AST, CKMB and LDH) values. As a result, increased IL-1β and TNF-α levels, proinflammatory cytokines, and some biochemical parameters may be reflect that long term used nandrolone decanoate causes organ damages and effect immune system function. However, effects of long term used nandrolone decanoate on the immune system and organ functions should be detailed evaluated.

Keywords

Nandrolone, Cytokines, Organ damages

Introduction

It is stated that use of doping has increased significantly in recent years, and it harms human health and at the same time, it also affects ethical values of sport negatively [1]. Doping refers to taking any impurity into body illegally by athletes in order to gain an advantage over competitor in contests and competitions [2]. After the competitions, a science committee follows traces of various performance enhancers with blood and urine tests. This is very important in terms of protecting justice of the sport with athletes [3]. The fight against doping has become a political issue around the world for more than 60 years [4].

While AAS (Anabolic androgenic steroids) which are ones of synthetic derivatives of male sex hormones and testosterone [5-8] had being used for burns and traumas, radiation therapy and chronic weight loss diseases since 1940s, They became even more important in treatments of AIDS related burnout syndrome and kidney diseases after 1985 [9].

It has been reported that anabolism takes part in enhancing protein synthesis to keep nitrogen in body mass [10], androgens take part in development of the male reproductive system [11].

Materials and Methods

Totally 35 male and 35 female rats were used. 5 male and female rats were accepted as control time (0 hour), and rested 30 male and female rats were received at the doze of 40 mg/kg nandrolone decanoate (IP). After treatments, blood samples were collected at 1, 2, 4, 8, 12 and 24 hour from cardiac puncture under anesthesia. Serum ALP, ALT, AST, CK-MB, GGT, LDH and BUN levels were measured with auto-analyzer, while serum TNF-α, IL-1β, IL-6 and IL-10 levels was determined with ELISA reader. Data were evaluated by ANOVA and Duncan test. P<0.05 was accepted as statistically significant.

Results

Serum biochemical values of male and female rat are shown in Tables 1 and 2, respectively. Increased GGT and BUN levels were determined (P<0.05) in male rats, whereas statistically significant fluctuations were determined (P<0.05) in ALP, GGT, BUN and LDH levels in female rats.

Parameters 0 h 1 h 2 h 4 h 8 h 12 h 24 h
ALP, U/L 120.6 ± 16.0 96.0 ± 10.6 138,5 ± 17.5 110,7 ± 14.5 113,4 ± 19.7 91.8 ± 19.3 116.7 ± 15,74
ALT, U/L 57.3 ± 5.71 52.0 ± 4.39 57.0 ± 4.14 63.8 ± 8.73 51.1 ± 6.95 48.0 ± 3.98 54.45 ± 6.46
AST, U/L 95.1 ± 16.5 100 ± 14.5 120 ± 19.7 154 ± 26.1 104 ± 13.30 94.0 ± 11.9 112.3 ± 14.4
CKMB, U/L 743 ± 160 806 ± 191 730 ± 263 1421 ± 474 674 ± 217 779 ± 251 952 ± 234
GGT, U/L 1.06 ± 0.16b 1.83 ± 0.40ab 2.33 ± 0.80ab 2.00 ± 0.36ab 1.50 ± 0.22ab 1.16 ± 0.16b 2.84 ± 0.66a
LDH, U/L 578 ± 87.7 485 ± 85.5 505 ± 164 731 ± 180 387 ± 55.2 461 ± 86.8 554 ± 148
BUN mg/dl 48.0 ± 1.54c 59.0 ± 3.93abc 54.3 ± 3.33abc 62.6 ± 3.45ab 51.1 ± 2.02bc 66.1 ± 2.46a 64.4 ± 4.6ab

Table 1. Serum biochemical parameters of male rats after Nandrolon decanoate treatment (mean ± SE).

Parameters 0 h 1 h 2 h 4 h 8 h 12 h 24 h
ALP, U/L 74.5 ± 2.98ab 68.6 ± 4.75b 69.3 ± 4.87ab 62.5 ± 11.4b 65.0 ± 8.98b 58.3 ± 4.91b 103 ± 11.9a
ALT, U/L 98.0 ± 28.6 126 ± 23.5 88.0 ± 21.0 72.6 ± 14.7 66.1 ± 5.81 79.0 ± 10.2 76.6 ± 15.0
AST, U/L 152 ± 24.4 205 ± 44.2 159 ± 28.3 122 ± 30.2 117 ± 15.5 154 ± 18.6 165 ± 30.1
CKMB,U/L 814 ± 187 1223 ± 575 843 ± 132 538 ± 49 778 ± 228 707 ± 198 1262 ± 580
GGT, U/L 2.16 ± 0.47ab 1.50 ± 0.22ab 1.16 ± 0.47b 1.66 ± 0.33ab 1.24 ± 0.22b 1.33 ± 0.21b 3.66 ± 0.98a
LDH, U/L 891 ± 101a 774 ± 154ab 523 ± 74ab 287 ± 43b 458 ± 142ab 573 ± 138ab 783 ± 182ab
BUN mg/dl 59.8 ± 12.7ab 48.6 ± 2.26b 59.3 ± 2.33ab 55.0 ± 3.84ab 54.6 ± 1.68ab 78.6 ± 4.33a 53.8 ± 1.88b

Table 2. Serum biochemical parameters of female rats after Nandrolon decanoate treatment (mean ± SE).

Serum cytokine levels are presented in Tables 3 and 4, respectively. Increased IL-1β levels are determined (P<0.05) in male rats, whereas statistically significant fluctuations were determined (P<0.05) in IL-6 levels. Increased IL-1β and decreased IL-6 levels were measured (P<0.05) in female rats.

Parameters 0 h 1 h 2 h 4 h 8 h 12 h 24 h
TNF-α 4.27 ± 0.76 4.54 ± 1.20 4.74 ± 1.34 4.40 ± 0.96 5.41 ± 1.74 6.08 ± 1.86 5.76 ± 1.44
IL-1β 7.52 ± 1.94b 7.24 ± 1.82b 9.68 ± 1.56a 8.74 ± 1.46ab 10.12 ± 2.94a 9.85 ± 1.44a 9.72 ± 1.52a
IL-6 24.48 ± 2.64a 24.90 ± 3.57a 20.48 ± 2.54a 17.1 ± 3.45ab 22.34 ± 5.60a 14.84 ± 3.86b 18.42 ± 2.78ab
IL-10 6.84 ± 1.08 6.76 ± 1.14 7.80 ± 1.06 8.08 ± 2.14 7.96 ± 3.08 8.48 ± 2.17 8.12 ± 2.64

Table 3. Serum cytokine levels of male rats after Nandrolon decanoate treatment (mean ± SE).

Parameters 0 h 1 h 2 h 4 h 8 h 12 h 24 h
TNF-α pg/mL 4.86 ± 0.42 4.78 ± 1.64 5.15 ± 1.06 5.60 ± 0.96 4.88 ± 1.47 5.90 ± 1.64 5.94 ± 1.86
IL-1β pg/mL 6.46 ± 1.25b 6.64 ± 1.48b 8.88 ± 1.94a 8.12 ± 2.15a 6.88 ± 1.06b 8.19 ± 1.22a 8.72 ± 2.92a
IL-6 pg/mL 20.12 ± 3.85a 19.46 ± 2.98a 18.42 ± 2.08a 16.54 ± 1.13a 17.55 ± 3.72a 16.57 ± 2.92ab 14.18 ± 2.44b
IL-10 pg/mL 6.78 ± 1.20 6.66 ± 2.16 7.84 ± 2.26 6.98 ± 2.14 7.89 ± 2.85 7.92 ± 3.02 8.06 ± 2.54

Table 4. Serum cytokine levels of female rats after Nandrolon decanoate treatment (mean ± SE).

Discussion

Today, sudden cardiac death due to cardiovascular disease takes an important place in causes of death [12]. Because use of anti-androgenic drugs for treatment in medicine have increased rates of death due to cardiovascular function [13,14], this situation has revealed that there is a need for more in-depth investigation of the effects of androgenic hormones. It has been seen that application of testosterone above physiological doses decreases eNOS activity and increases oxidative stress [15]. As a matter of fact, in relation to the research done, it is reported that rate of death due to cardiovascular diseases has increased among ones misusing androgens and the reason of this might be due to endothelial dysfunction occurring [16].

Although it is reported that nandrolone decanoate increases TNFα, IL-1β and IL-4 production in cell cultures and suppresses IL-6 mRNA expression [17-19], in some studies, it has been determined that it has no effect on TNFα and IL-1β mRNA expression and IL-2, IL-3 and IL-10 productions [18,20,21]. On the other hand, it has been reported that AAS inhibit activation of nuclear factor Kappa B (NF-κB) [22] allowing expression of genes encoding proinflammatory cytokines [23].

The study done has shown that there is no statistical difference related to serum cytokine levels between male and female rats during first 24 h. After administration of ND, it has been determined in both genders that IL1-β levels increased after 2 h following administration (p<0.05) and non-statistical numerical increase in TNF-α levels was observed. It has been seen that results obtained are compatible with findings of some researchers [17-19], they are not compatible with findings of Corrales et al. stating that there is a decrease in IL1-β and TNF-α levels in individuals receiving testosterone therapy. It has been interpreted that ND has much more androgenic effects than testosterone and this is the reason of using high dose of ND in the study and also 24-hour variation might vary. Also, Parrillo et al. and Dinarello have reported that IL1-β and TNF- α levels might be associated with multiple organ failure. In the light of this information, it has been thought that these increases observed in these two cytokines might be sign of results that may cause multiple organ failures.

In the study done, decreases in serum IL-6 levels have been observed in male and female rats during the h following ND administration and it has been observed that this decrease is compatible with some studies [17-19]. There has not been any change observed in IL-10 levels in male and female rats as compatible with findings of Thompson et al. and when results have been analyzed, it has been seen that although it doesn't make statistical sense, there is numerical increase as compatible with statements of Corrales et al.

In many studies in which effects of ASS on liver enzymes were researched, enzyme activities were examined and different results were obtained in terms of these activities [20-26]. In some studies, any change has not been stated in AAS applications [27,28], but there has been some studies stating increases in AST and ALT activities [27,29-31].

In the study done, while hourly variation in any parameter has not been observed in male rats except GGT and BUN levels, this situation is also accompanied by ALP in females (Tables 4.1 and 4.2). However, when biochemical parameters are examined, there is numerical increase in especially AST and CK-MB levels in terms of h. Even if changes in biochemical parameters occurring in the first 24 h don't support increase in IL1-b and TNF-α levels completely, this has been thought as sign showing that ND applications will lead to various multiple organ failures particularly liver failure. As a matter of fact, although treatment was used in appropriate dose in a study in which ND was administered [32], with findings obtained at the end of 4 weeks, it was concluded that multiple organ failure might be encountered in rats.

Conclusion

As a result, it has been thought that these values are needed to be monitored longer than 24 h in order to understand changes in serum cytokine levels and biochemical parameters examined more clearly.

Acknowledgement

This study was supported by the scientific research coordinator SUBAPK (10401125). A part of the abstract was presented at the “13th International Congress of sport sciences” 07-9 November 2014, Konya,Turkey.

References