Gebelikte Tütün Dumanı Maruziyetinin Anne Sıçan Böbrek Dokusunda Meydana Getirdiği Değişiklikler Üzerine Alfa Lipoik Asitin Etkilerinin İncelenmesi

Year 2019, Volume: 14 Issue: 1, 52 - 63, 28.04.2019

Elif Erdem Güzel , Nalan Kaya , Gonca Ozan Kocamüftüoğlu DÜRRİN ÖZLEM Dabak PENBE SEMA Temizer Ozan , İBRAHİM ENVER Ozan

https://doi.org/10.17094/ataunivbd.407782

Abstract

Çalışmada gebelikte tütün dumanına maruz kalan anne sıçanların böbrek dokusunda meydana gelen histopatolojik sonuçlar üzerine Alfa lipoik asitin etkilerinin deneysel olarak araştırılması amaçlandı. 28 adet dişi Sprague-Dawley cinsi sıçan kullanıldı. Gebe sıçanlar; Kontrol grubu, Tütün dumanı (TD) grubu, Tütün dumanı + Alfa lipoik asit (TD+ALA) grubu ve Alfa lipoik asit (ALA) grubu olmak üzere rastgele dört eşit gruba ayrıldı. TD ve TD+ALA grubundaki sıçanlar çiftleşmeden önce sekiz hafta ve gebelik süresince günde iki saat tütün dumanına maruz bırakıldı. TD+ALA ve ALA grubundaki sıçanlara ise çiftleşmeden önce sekiz hafta ve gebelik süresince gün aşırı gavaj yolu ile 20 mg/kg ALA verildi. Deney sonunda çıkarılan böbrek dokuları histolojik, immünohistokimyasal ve MDA düzeyi tayini metotları kullanılarak incelendi. TD grubuna ait böbrek kesitlerinde inflamatuar hücre artışı, Bowman boşluğunda artış, tübül lümeninde hiyalin birikimi gibi histopatolojik bulgulara rastlandı. ALA uygulaması ile histopatalojik bulguların büyük bir çoğunluğunda azalma gözlendi. TD grubunda VEGF immünreaktivitesinin kontrol grubuna göre anlamlı artış gösterdiği, TD+ALA grubunda ise TD grubuna göre anlamlı derecede azaldığı belirlendi. MDA seviyelerinde ise TD grubunda, kontrol grubuna göre anlamlı artış olduğu tespit edildi. Sonuç olarak, gebelik boyunca tütün dumanı maruziyetinin böbrek dokularında histopatolojik hasara ve damarlanmada artışa neden olduğu, ALA’nın ise bu etkilere karşı kısmen koruma sağladığı belirlendi.

Keywords

Alfa Lipoik Asit, Böbrek, Gebelik, Sıçan, Tütün Dumanı

Investigation of the Effects of Alfa Lipoic Acid on Changes in Maternal Rat Kidney Caused by Tobacco Smoke Exposure in Pregnancy

Abstract

The aim of this study was to investigate the effects of alpha lipoic acid on histopathological results of kidney tissue of mothers exposed to tobacco smoke during pregnancy. Twenty-eight Spraque-Dawley female rats were used. Rats were randomly divided into four groups: control, tobacco smoke (TS), tobacco smoke + alpha lipoic acid (TS+ALA) and alpha lipoic acid (ALA). Rats in the TS and TS+ALA groups were exposed to TS twice a day for one hour starting from eight weeks before mating and during pregnancy. 20 mg/kg of ALA was administered by gavage to ALA and TS+ALA group. The kidney tissues were examined by histological, immunohistochemical and MDA levels. Histopathological findings such as inflammatory cell increase, enlargement Bowman distance and hyaline casts in the tubule lumen were observed in the TS group. ALA application was found to reduce the majority of histopathological findings. VEGF immunoreactivity was significantly increased in the TS group compared to the control group, whereas in the TS+ALA group, VEGF immunoreactivity was significantly lower than TS group. MDA levels were significantly increased in the TS group compared to the control group. As a result, it has been shown that exposure of tobacco smoke during pregnancy causes an increase in histopathologic damage and vascularity in kidney tissues and that alpha lipoic acid has a partially protective effect against this effects.

Keywords

Alpha Lipoic Acid, Kidney, Pregnancy, Rat, Tobacco Smoke

References

• Referans1. Vanker A., Gie RP., Zar H1.,2017.The association between environmental tobacco smoke exposure and childhood respiratory disease: a review. Expert Rev Respir Med,11,661-673.Referans2.Thielen A., Klus H., Muller L.,2008. Tobacco smoke: unraveling a controversial subject. Exp. Toxicol. Pathol, 60,141–156. Referans3. Keith RJ., Rifai M., Defilippis AP.,2016. Tobacco Use, Insulin Resistance, and Risk of Type 2 Diabetes: Results from the Multi-Ethnic Study of Atherosclerosis. PLos ONE,11,1-24.Referans4. Lucini D., Bertocchi F., Malliani A., Pagani M.,1996. A controlled study of the autonomic changes produced by habitual cigarette smoking in healthy subjects. Cardiovascular Research, 31,633–9.Referans5. Karcaaltincaba D., Kandemir Ö., Yalvac S., Güvendağ Güven ES., Yildirim BA., Haberal A.,2009. Cigarette smoking and pregnancy: results of a survey at a turkish women's hospital in 1,020 patients. J Obstet Gynaecol, 29,480- 486.Referans6. Niemann B., Rohrbach S., Miller MR., Newby DE., Fuster V., Kovacic JC.,2017.Oxidative Stress and Cardiovascular Risk: Obesity, Diabetes, Smoking, and Pollution: Part 3 of a 3-Part Series. J Am Coll Cardiol,70,230-251.Referans7. Blann AD., McCollum CN., 1993. Adverse Influence of Cigarette Smoking on the Endothelium. Thrombosis and Haemostasis, 70, 707-711.Referans8. Boor P., Casper S., Celec P., 2009. Renal, vascular and cardiac fibrosis in rats exposed to passive smoking and industrial dust fibre amosite. J Cell Mol Med, 13, 4484–4491.Referans9. Shibuya M. Vascular endothelial growth factordependent and -independent regulation of angiogenesis,2008. BMB Rep, 41,278-286.Referans10. Wang Y., Zang QS., Liu Z., Wu Q., Maass D., Dulan G.,. Shaul PW., Melito L., Frantz DE., Kilgore JA., Williams NS., Terada, LS., Nwariaku FE.,2011. Regulation of VEGF-induced endothelial cell migration by mitochondrial reactive oxygen species. Am J Physiol Cell Physiol,301,695-704.Referans11. Ushio-Fukai M., Tang Y., Fukai T., Dikalov SI., Ma Y., Fujimoto M., Quinn MT., Pagano PJ., Johnson C., Alexander RW.,2002. Novel role of gp91(phox)-containing NAD(P)H oxidase in vascular endothelial growth factor-induced signaling and angiogenesis. Circ Res, 91,1160-1167.Referans12. Takaoka M., Ohkita M., Kobayashi Y., Yuba M., Matsumura Y.,2002. Protective effect of alpha-lipoic acid against ischaemic acute renal failure in rats . Clin. Exp. Pharmacol. Physiol,29, 189 – 194.Referans13. Al Ghafli MHM., Padmanabhan R., Kataya HH., Berg B.,2004. Effects of α-lipoic acid supplementation on maternal diabetes-induced growth retardation and congenital anomalies in rat foetuses. Mol cell Biochem,1–13. Referans14. Placer ZA., Cushmann LL., Johnson BC.,1966. Estimation of products of lipid peroxidation (as malondialdehyde) in biochemical systems. Analytical Biochemistry, 16, 359-364.Referans15. Ejerblad E., Fored CM., Lindblad P., Fryzek J., Dickman PW., Elinder CG., McLaughlin JK., Nyrén O.,2004. Association between smoking and chronic renal failure in a nationwide population-based case-control study. J Am Soc Nephrol, 15,2178-85.Referans16. Mercado C., Jaimes EA.,2007. Cigarette smoking as a risk factor for atherosclerosis and renal disease: novel pathogenic insights. Curr Hypertens Rep, 9, 66-72.Referans17. Xie X., Liu Q., Wu J., Wakui M., 2009. Impact of cigarette smoking in type 2 diabetes development. Acta Pharmacol Sin, 30, 784–787.Referans18. Bickerstaff M., Beckmann M.,Gibbons K., Flenady V.,2012. Recent cessation of smoking and its effect on pregnancy outcomes. Aust. N. Z. J. Obstet. Gynaecol, 52, 54–58.Referans19. Terry PD., Weiderpass E., Ostenson C., Cnattingius S.,2003. Cigarette smoking and the risk of gestational diabetes and pregestational diabetes in two consecutive pregnancies. Diabetes Care,26,2994-8.Referans20. Zhang C., Tobias DK., Chavarro JE., Bao W., Wang D., Ley SH., Hu FB., 2014. Adherence to healthy lifestyle and risk of gestational diabetes mellitus: prospective cohort study. BMJ,349,1-25.Referans21. Cooper RG.,2006. Effect of tobacco smoking on renal function. Indian J Med,124,261-268.Referans22. Orth SR.,2000. Smoking--a renal risk factor. Nephron,86, 12-26.Referans23. Rahman MM., Laher I.,2007. Structural and functional alteration of blood vessels caused by cigarette smoking: an overview of molecular mechanisms. Curr vasc Pharmacology,5,276-292.Referans24. Csiszar A., Podlutsky A., Wolin MS., Losonczy G., Pacher P., Ungvari Z.,2009. Oxidative stress and accelerated vascula raging:implications for cigarette smoking. Front Biosci, 14,3128-3144.Referans25. Fakhruddin S., Alanazi WA., Jackson KE.,2017.Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury. J Diabetes Res,1-30.Referans26. Şahin E., Demirci T., Gedikli S.,2017. Kronik Stres ve Böbrek: Sıçan Modeli Üzerinde Morfometrik ve Histopatolojik Çalışma. Sakarya Tıp Dergisi,7,168-175.Referans27. Adedayo AD.,Tijani AA., Adeniyi TD.,2011. Histological Study of Smoke Extract of Tobacco Nicotiana on the Heart, Liver, Lungs, Kidney, and Testes of Male Sprague-Dawley Rats. Niger Med J,52,217-222.Referans28. Hultberg B., Isaksson A., Brattström L., Israelsson B.,1992. Elevated urinary excretion of betahexosaminidase in smokers. Eur J Clin Chem Clin Biochem, 30,131-133.Referans29. Kumari S., Badana AK.,, Murali MG., Shailender G., Malla R.,2018. Reactive Oxygen Species: A Key Constituent in Cancer Survival. Biomarker Insights,13,1–9.Referans30. Stevens A., Lowe J.,2005. Human Histology. 3rd ed.,232, Elsevier Mosby, Philadelphia. 2005.Referans31. Hayman SR., Leung N., Grande JP., Garovic VD.,2012. VEGF Inhibition, Hypertension, and Renal Toxicity Curr Oncol Rep,14,285–294. Referans32. Cha DR., Kım NH., Yoon JW, Jo SK., Cho WY., Kim HK., Won NH.,2000. Role of vascular endothelial growth factor in diabetic nephropathy. Kidney Int,58,104–112.Referans33. Whittle C., Gillespie K., Harrison R., Mathieson PW., Harper SJ.,1999. Heterogeneous vascular endothelial growth factor (VEGF) isoform mRNA and receptor mRNA expression in human glomeruli, and the identification of VEGF148 mRNA, a novel truncated splice variant. Clin Sci,97,303–312.Referans34. Dvorak HF.,2001. Vascular permeability factor/vascular endothelial growth factor: A critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol,20,4368–4380.Referans35. Heeschen C., Jang JJ., Pathak A., Kaji S., Hu BS., Tsao P., Johnson F., Cooke JP.,2001. Nicotine is an agent of angiogenesis: a pathophysiological link to cancer and atherosclerosis. Nat Med,7, 833-839.Referans36. Conklin BS., Zhao W., Zhong DS., Chen C.,2002. Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells. Am J Pathol,160, 413-418.Referans37. Ushio-Fukai M., Alexander RW.,2004. Reactive oxygen species as mediators of angiogenesis signaling:role of NAD(P)H oxidase. Mol Cell Biochem,264,85-97.Referans38. Kaner RJ., Ladetto JV., Singh R., Fukuda N., Matthay MA., Crystal RG.,2000. Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am. J. Respir. Cell Mol. Biol,22, 657–664.Referans39. Brausewetter F., Jehle PM., Jung MF., Boehm BO., Brueckel J., Hombach V., Osterhues HH.,2001. Microvascular permeability is increased in both types of diabetes and correlates differentially with serum levels of insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF). Horm Metab Res,33,713–720.Referans40. de Vriese AS., Tilton RG., Elger M., Stephan CC., Kriz W., Lameire NH.,2001. Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol, 12,993–1000.Referans41. Veron D., Reidy KJ., Bertuccio C., Teichman J., Villegas G., Jimenez J., Shen W., Kopp JB., Thomas DB., Tufro A.,2010. Overexpression of VEGF‐A in podocytes of adult mice causes glomerular disease.Kidney Int,77, 989‐999.Referans42. Schrıjvers BF., Flyvbjerg A., VRIESE AS.,2004. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney International, 65,2003–2017.Referans43. Krueger JK., Rohrich RJ.,2001. Clearing the smoke: The scientific rationale for tobacco abstention with plastic surgery. Plast Reconstr Surg,108,1063-73.Referans44. KIRAL F., ULUTAS PA., FIDANCI UR.,2008. Lipid peroxidation and antioxidant enzymes in rats exposed to cigarette smoke. Ankara Üniv Vet Fak Derg, 55, 145-148.Referans45. Phaniendra A., Jestadi DB., Periyasamy L.,2015. Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases. Indian J Clin Biochem,30,11-26. Referans46. Çakır T., Polat C., Baştürk A., Gül M., Aslaner A., Durgut H., Şehirli AÖ., Aykaç A., Bahar L., Sabuncuoglu MZ.,2015.The effect of alpha lipoic acid on rat kidneys in methotrexate induced oxidative injury. Eur Rev Med Pharmacol Sci,19,2132-9.