الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
Infertility is a major health problem affecting 15% of couples in reproductive age group. The male partner is contributory in up to 50% of cases. Growing evidence from clinical and epidemiological studies suggests an increasing incidence of male reproductive problems. The pathogenesis of male infertility can be reflected by defective spermatogenesis due to pituitary disorders, testicular oxidative stress, germ cell aplasia, varicocele and environmental factors. Stressors like smoking nicotine and obesity deeply affect male reproduction.
The relation between obesity and infertility is well documented as obesity has the ability to initiate a secondary hypogonadism by affecting male sex hormones, oxidative stress markers, lipid profile and inflammatory mediators.
Nicotine is a natural ingredient in tobacco leaves which is the major alkaloidal component in cigarettes. It is believed that smoking nicotine is an important cause of male infertility by its negative action on sex hormones, testicular tissue damage, and depletion of body defence enzymes.
The present study aimed to:
1- Elucidate the effect of nicotine and obesity on male sex hormones, oxidative stress, lipid profile and inflammatory mediators.
2- Examine the possible protective effect of either vitamin E or garlic in combination form with nicotine on the studied parameters.
3- Investigate the possible correlations between the studied biochemical parameters.
4- Examine the histopathological changes in testicular tissues following supplementation of nicotine individually or in combined form with vitamin E or garlic.
Selected biochemical parameters to fulfill such requirement were:
1- In serum: testosterone, follicle stimulating hormones (FSH), leuitinizing hormones (LH) and lipid profile.
2- In hepatic tissues: reduced glutathione hydrogenase (GSH), super oxide dismutase (SOD), catalase and malondialdehyde (MDA).
3- In testicular sections: immunohistochemical detection of cycloxygenase-2(COX-2) and 5- lipoxygenase (5-LOX).
Representative samples of testicular tissues were processed for histopathological examination using light microscope, to configurate tissue changes and explore their possible correlations with the selected biochemical parameters.
Experimental Design:
One week after acclimatization, 160 rats were divided into 2 main groups (n=80, each) normal group and obese group.
Part I: Normal rats:
Supplied with standard diet and subdivided into 4 subgroups:
Subgroup (1):
Received saline daily for 6 weeks, utilized as control, (n=20).
Subgroup (2):
Received nicotine (2.5 mg/kg/day) for 6 weeks, by intraperitoneal injection, (n=20).
Subgroup (3):
Received vit E orally (100 mg/kg/day) dissolved in olive oil as a prophylactic dose for 2 weeks, then both vit E (100 mg/kg/day) and nicotine (2.5 mg/kg/day) were supplemented for 4 weeks, (n=20).
Subgroup (4):
Received garlic powder orally (100 mg/kg/day) body weight daily suspended in distilled water for 2 weeks as a prophylactic dose, then both garlic powder (100 mg/kg/day) and nicotine (2.5 mg/kg/day) were given for 4 weeks, (n=20).
Part II: Obese rats:
Rats rendered obese by supplementation with high fat diet and intra lipid 10% for 14 weeks, then subdivided into 4 subgroups:
Subgroup (1):
Received High fat diet and intralipid (10%) for 14 weeks and utilized as control, (n=20).
subgroup (2):
Obese rats received nicotine orally (2.5 mg/kg/day) for 6 weeks with continuous high fat diet and intralipid, (n=20).
Subgroup (3):
Obese rats, received vit E orally (100 mg/kg/day) dissolved in olive oil as a prophylactic dose for 2 weeks ,Then both vit E (100 mg/kg/day) and nicotine (2.5 mg/kg/day) were given for 4 week in addition to high fat diet and intralipid, (n=20).
Subgroup (4):
Obese rats received garlic powder orally (100 mg/kg/day) suspended in distilled water as a prophylactic dose for 2 weeks, then both garlic (100 mg/kg/day) and nicotine (2.5 mg/kg/day) were given for 4 weeks. They were fed high fat diet and Intralipid, (n=20).
Results:
Normal rats received nicotine demonstrated significant decrease in serum testosterone, FSH, LH, HDL-c and hepatic (GSH, SOD, catalase). Meanwhile, serum lipid profile (TC, TAG and LDL-c) were markedly increased as compared to control rats. Immunohistochemistry of testicular tissues indicated a remarkable increase in biosynthesis of COX-2 and 5-LOX.
Histopathological examination of testicular tissues indicated that nicotine administration induced distortion of seminiferous tubules. These tubules have wide lumina& reduced epithelial lining. Few sperms and desquamated cells are seen in their lumina.
Garlic in combination with nicotine increased serum level of testosterone, FSH, LH, HDL-c and improved oxidative stress parameters (GSH, SOD, catalase and MDA). On the other hand, a significant decrement in serum TC, TAG, LDL-c levels was detected.
Immunohistochemistry of testicular tissues indicated a slight decrease in COX-2 and 5-LOX levels.
Histopathological examination of testicular tissues indicated that, intake of garlic in combination with nicotine resulted in an improvement as most of the seminiferous tubules appears relatively normal, and fewer ones still have abnormal lining and empty lumina.
Intake of nicotine-vitamin E combined form induced an increase in serum level of testosterone, FSH, LH, HDL-c and improved oxidative stress parameters (GSH, SOD, catalase and MDA), and significantly reduced TC, TAG, LDL-c levels.
Immunohistochemistry of testicular tissues indicated that rats treated with nicotine-vitamin E combined form still have a remarkable increase in biosynthesis of COX-2 and 5-LOX.
Histopathological examination of testicular tissues demonstrated that, rats treated with nicotine and vit E, showed that some seminiferous tubules have normal epithelial lining and sperms in their lumina while others still have reduced epithelial lining and empty lumina.
Rats received high fat diet showed a remarkable reduction in sex hormones (testosterone, FSH, LH), scavenging enzymes (SOD, catalase, GSH) and HDL-c compared with control group. On the other hand, significant elevations in TC, TAG, LDL-c and MDA levels were demonstrated.
Immunohistochemistry of testicular tissues showed that obesity alone cannot elevate COX-2 and 5-LOX expressions, meanwhile obese rats treated with nicotine showed a remarkable increase in their expressions compared with normal rats treated with nicotine.
Histopathological examination of testicular tissues of obese rats indicated that, obesity resulted in distorted seminiferous tubules, with reduced epithelial lining and empty lumina. Wide separation between the cells and few sperms are noticed in some tubules. .
Obese rats treated with nicotine illustrated significant reduction in serum testosterone, FSH, LH and HDL-c and lower hepatic GSH, catalase and SOD as compared to control obese group.
Nicotine injection induced a significant elevation in serum TC, TAG, LDL-c and MDA levels in obese rats.
Immunohistochemistry of testicular tissues showed that obese rats treated with nicotine demonstrated highly significant increase in COX-2 and 5-LOX levels.
Histopathological examination of testicular tissues of obese rats treated with nicotine showed that most tubules are lined with reduced epithelium and have empty lumina. Wide separation between cells can be noticed in some tubules with exfoliated cells in the lumina.
Obese rats treated with garlic in combination with nicotine showed a significant improvement in male sex hormone levels (testosterone, FSH, LH), oxidative stress markers (GSH, catalase, SOD) and HDL-c.
In contrary, significant reduction in serum TC, TAG, LDL-c and MDA levels were elucidated.
Immunohistochemistry of testicular tissues of obese rats treated with garlic in combination with nicotine indicated that there is lower COX-2 and 5-LOX levels can be noticed.
Histopathological examination of testicular tissues of obese rats treated with garlic in combination with nicotine demonstrated that most of seminiferous tubules have normal stratification of their epithelial lining.
Obese rats treated with vitamin E in combination with nicotine showed significant increment in male sex hormone levels (testosterone, FSH, LH), oxidative stress markers (GSH, catalase, SOD) and HDL-c.
On the other hand, significant decrements in serum levels of TC, TAG, LDL-c and MDA were observed.
Immunohistochemistry of testicular tissues of obese rats treated with vitamin E in combination with nicotine indicated that there is no change in COX-2 and 5-LOX levels as compared with obese nicotine treated ones.
Histopathological examination of testicular tissues of obese rats treated with vitamin E in combination with nicotine demonstrated that some seminiferous tubules with stratification of their epithelial lining. Others still have disorganized epithelial lining and few sperms in the lumina.
Using the combined results from all treated animals, serum level of total testosterone recorded positive correlation with serum FSH, serum LH, serum HDL-c and hepatic SOD.
On the other hand it was negatively correlated with hepatic MDA.
Conclusion:
Taken together, the results reported in this study suggested that nicotine administration induced hypogonadism as illustrated by decreased sex hormones levels (testosterone, FSH and LH), depletion of antioxidants, dyslipidemia and remarkable increase in inflammatory mediators.
High fat diet administration to experimental rats induced evident high body weight joined with significant reduction in male sex hormones (testosterone, FSH and LH), increased oxidative stress, disturbed lipogram pattern and increased inflammatory markers.
Vitamin E-nicotine co-therapy demonstrated a protective effect; it significantly elevated serum testosterone, FSH and LH levels, improved the disturbed lipogram pattern, increased antioxidants but not affect inflammatory mediators.
Garlic supplementation in combination with nicotine showed a protective effect. This was illustrated by increased sex hormones levels, decreased oxidative stress markers, improvement in lipogram pattern and reduced inflammatory mediators.
In conclusion, and parallel to the current results, it is evident that nicotine administration and obesity may cause a secondary hypogonadism associated with hyperlipidemia and damage of testicular tissue which are mediated by inflammation and oxidative stress.
This current study recommended dietary supplementation of garlic for obese smoking male to limit associated infertility through improving male gonadal function, lipogram pattern, decreased oxidative stress markers and reduced inflammatory mediators.
Obviously, further studies are required to provide mechanistic insight as well as potential therapeutic benefit.