The Effects of Alpha Lipoic Acid on Bladder Contractility, Histopathologic Changes and Oxidant/Antioxidant Systems on Experimental Rats with Metabolic Syndrom

Abstract

Objective: To investigate effect of Alpha Lipoic acid (α-LA) on bladder function of experimental rats with metabolic syndrom. Material and Method: In this study, 40 Wistar Albino rats with a mean weight of 180- 200 gr were used. They were divided into four equal groups (n=10). Group I was considered as the control group. The other 3 groups were feeded with 60% fructose enriched diet for 6 weeks. After achieving MetS saline (SF) and α-LA was injected intraperitonealy (i.p.) for 6 weeks to the rats in the group II and III respectively. Group IV received α-LA (i.p.) for 12 weeks. Then all the rats were decapitated and their blood and tissue samples were collected. Plasma triglyceride, LDL, HDL, total cholesterol, glucose and insülin levels, the ratio of total oxidant to total antioxidant level were measured. Routine histological techniques was performe to the bladder tissues from experimental rats and -vitro contraction activity were measured. Results: Plasma glucose, TG, LDL, TOS levels, were decreased and HDL level was increased in the groups with α-LA admission compared to Group II. Plasma TOS levels of Group IV was decreased and the maximum percentage of contractional response of Group IV has increased in group IV compared to Group II. And according to histopathological evaluation the mean number of the vessels in Group II was significantly higher than in the control. Conclusion: It has shown that exogenous α-LA therapy decreases the bladder dysfunction due to metabolic syndrome and improve the response of contractions, and amplitude significantly.

Keywords

• Metabolic syndrome, Bladder, Alpha lipoic acid, Contractility.

Deneysel Metabolik Sendrom Oluşturulan Ratlarda Alfa Lipoik Asit Kullanımının Mesane Kontraktilitesi, Histopatolojik Değişimler ve Oksidan/Antioksidan Sistem Üzerine Olan Etkileri

Öz

Amaç: Metabolik sendrom (MetS) oluşturulan deneysel modelde alfa lipoik asit (α-LA) kullanımının mesane fonksiyonları üzerine olan etkisini araştırmak. Gereç ve Yöntem: Çalışmada 180- 200 gram ağırlığında 40 adet Wistar Albino cinsi rat kullanıldı. Deney hayvanları her grupta 10 hayvan olacak şekilde 4 gruba ayrıldı. Kontrol grubuna (grup 1) herhangi bir işlem yapılmadı. Diğer üç gruba toplam 6 hafta boyunca %60'lık fruktozla zenginleştirilmiş diyet verilip MetS oluşturulduktan sonra grup II'ye 6 hafta süreyle intraperitoneal (i.p.) serum fizyolojik (SF), grup III'e 6 hafta süre ile α-LA (i.p.), Grup IV'e ise 12 hafta i.p α-LA verildi. Çalışma sonucu ratlar dekapite edilerek serum örneklerinde; trigliserit (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), total kolesterol, glukoz ve insülin düzeyleri, total oksidan seviye/total antioksidan seviyeleri (TOS/TAS) çalışıldı. Deney hayvanlarından alınan mesane dokularına rutin histolojik teknikler uygulandı ve in-vitro kontraksiyon aktivitesi ölçüldü. Bulgular: Grup II ile kıyaslandığında α-LA uygulanan gruplardaki serum glukoz, TG, LDL değerlerinin azaldığı, HDL değerlerinin ise arttığı istatistiksel olarak belirlendi. Grup IV'ün total oksidan seviye değerindeki azalmanın istatistiksel olarak anlamlı olduğu, kontraksiyon yanıtının grup II'ye göre istatististiksel olarak anlamlı oranda arttığı tespit edildi. Ayrıca histopatolojik değerlendirmeye göre grup IV'ün ortalama damar sayısının grup II'ye göre anlamlı olarak az olduğu görüldü. Sonuç: Metabolik sendromun neden olduğu mesane disfonksiyonu ve tedavisinde α-LA kullanımının, mesane disfonksiyonunu azalttığı ve kontraksiyon ve amplitüd yanıtı üzerinde anlamlı iyileşmeye yol açtığı gözlendi.

Anahtar Kelimeler

• Metabolik sendrom, Mesane, Alfa lipoik asit, Kontraktilite.

References

1. Moul S, McVary KT. Lower urinary tract symptomps, obesity and the metabolic syndrome. Curr Opin Urol 2010; 20: 7-12.
2. Sand PK, Dmochowski R. Analysis of the standardisation of terminology of lower urinary tract dysfunction: report from the standardization subcommittee of the international continence society. Neurourol Urodyn 2002; 21: 167-78.
3. Abrams P, Blavias JG, Stanton SL, et al. The standardisation of terminology of lower urinary tract function. The International Continence Society Committee on Standardisation of Terminology. Scand J Urol Nephrol Suppl 1988; 114: 5-19.
4. Kreder K, Dmochowski R. Aşırı aktif mesane değerlendirme ve tedavi.1.Baskı, Ankara: Güneş tıp kitap evleri, 2010: 6-9.
5. Tai HC, Chung SD, Ho CH, et al. Metabolic syndrome components worsen lower urinary tract symptoms in women with type 2 diabetes. J Clin Metab 2010; 95: 1143-50.
6. Oğuz A. Kardiyovasküler hastalıkların patogenezinde, önlenmesinde ve tedavisinde doku renin anjiyotensin sistemi. Baskı, İstanbul: Mas Matbaacılık, 2002.
7. Tinel H, Stelte-Ludwig B, Hütter J, et al. Pre-clinical evidence for the use of phosphodiesterase- 5 inhibitors for treating benign prostatic hyperplasia and lower urinary tract symptoms. BJU Int 2006; 98: 1259-63.
8. Dmochowski R, Roehrborn C, Klise S, et al. Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial. J Urol 2010; 183: 1092-7

9. Lee WJ, Park JY, Lee KU. α-Lipoic acid prevents diabetes mellitus and endothelial dysfunction in diabetes-prone obese rats. Packer L, Sies H (editörs). Oxidative stress and ınflammatory mechanisms in obesity, diabetes and the metabolic syndrome. 1.Baskı, Newyork: CRC Press, 2008: 261-89. 11
10. Pershadsingh HA. Alpha-lipoic acid: physiologic mechanisms and indications for the treatment of metabolic syndrome. Expert Opin Investig Drugs 2007; 16: 291-302.
11. Tong YC, Cheng JT. Alterations of M2,3- muscarinic receptor protein and mRNA expression in the bladder of the fructose fed obese rat. J Urol 2007; 178: 1537.
12. Bhatti F, Mankhey RW, Asico L, et al. Mechanisms of antioxidant and pro-oxidant effects of alphalipoic acid in the diabetic and nondiabetic kidney. Kideny Int 2005; 67: 1371-80.
13. Shotton HR, Broadbent S, Lincoln J. Prevention and partial reversal of diabetes-induced changes in enteric nerves of the rat ileum by combined treatment with alpha-lipoid acid and evening primrose oil. Auton Neurosci 2004; 111: 57-65.
14. Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care 2006; 29: 2365-70.
15. Ametov AS, Barinov A, Dyck PJ, et al. The sensory symptoms of diabetic polyneuropathy are improved with α-lipoid acid: the SYDNEY trial. Diabetes Care 2003; 26: 770-6.
16. Levin RM, Danek M, Whitbeck C, et al. Effect of ethanol on the esponse of the rat urinary bladder to in vitro ischemia: protective fect of -lipoic acid. Mol Cell Biochem 2005; 271: 133
17. Halliwell B. Gutteridge JMC. Free radicals in biology and medicine, 2.baskı, Oxford: Clarendon Press 1989.
18. Zeng M, Zhang H, Lowell C, et al. Tumor necrosis factoralpha- induced leukocyte adhesion and microvessel permeability. Am J Physiol Heart Circ Physiol 2002; 283: H2420.