Buradasınız

DENEYSEL DÎYABETÎK NEFROPATÎDE ENALAPRİL VE L-KARNİTİN ETKİLERİ

EFFECTS OF ENALAPRİL AND L-CARNITINE IN EXPERIMANTAL DIABETIC NEPHROPATHY

Journal Name:

Publication Year:

Keywords (Original Language):

Abstract (2. Language): 
Hyperglisemia, increased angiotensin II ATİ reseptör activity, oksidativestress, decreasing intracellular ATP play an important rol in occurance diabetic nephropathy (DN). In our study, effects of angiotensin converting enzyme inhibitor (ACEi) as enalapril (EN), and L-Carnitine (LC) were investigated on DN in streptozotocin-induced diabetic rats. Except healthy, patient control (HK, PK) groups, 2.5mg/kg/day EN and 100 mg/kg/day LC were given in a water for six weeks. After 24 hrs urine collection, bloodwith-drownedby cardiacpunction then, rats were sucrified. Erythrocytes count (Er), hemoglobin (Hb), hematocrit (Hct) in blood; and glucose, HbAlc, urea, creatinine (pCr), uric acid (UA), P04, Ca2*, Na, K*, albumin (Alb) in plasma;superokside dismutase enzyme (SOD) as an antioxidant, malonyl dialdehyte (MDA) as lipidperoxidationproduct (ROS) were measured in eryhtrocyte were measured. Daily excretion of urinary glucose (UG), albumin (UAE), N-acetyl-b-D-glucosaminidase (NAG) were measured. FractionalNa*(FANA) excretion and GFR were calculated. İmmunuhistochemical kollagene type IV accumulation and renal histopathology were investigated on light microscopy. After STZ injection DN was established with increased glucose, HbAlc, UG, UAE, NAG (P<.000), urea, pKr (P<005). According to PKgroup, lower UG (P<000), NAG, urine volume, P04, and higher Alb (P<05) in EN group, higher Er, Hb, lower urine volume, UG, NAG (P<.05) in LC groups were found. According to HK, nonsignificant increased MDA in PK, unchanged in EN and LC groups were found. Tubulo-glomerular basal membrane thickness and accumulation tip IVkollagen as DN findings significant in PK, moderate EN, and mild degree in LC group were found. Ourfindings suggests that, LC have protective effect on diabetic nephropathy like ACEi.
Abstract (Original Language): 
Diabetik nefropati (DN) oluşmasında hiperglisemi, anjiotensin II ATİ reseptör aktivasyon ve oksidatif stres artısı, hücre içi ATP azalması önemli rol alır. Çalışmamızda, streptozosin (STZ) ile diyabet oluşturulan rotlarda anjiotensin /converting enzim inhibitörü (ACEi) olan Enalapril (EN) ve L-Karnitin (LK) in DNye etkileri araştırıldı. Dokuz ratlıkgruplarda, sağlıklı (SK) ve hastalıklı (HK) kontrol dışındakilere içme suyu ile 2.5 mg/kg gün EN velOO mg/kg/gün LK altı hafta verildi. Çalışma sonunda 24st lik idrar toplandı, kardiak ponksiyonla kan alınarak ratlar sakrifiye edildi. Kanda; eritrosit sayısı (Er), hemoglobin (Hb), hematokrit (Hct), plazmada;glukoz, HbAlC, üre, kreatinin (pKr), ürik asit (ÛA), PO4, Ca2*, Na\K+, albumin (Alb) ve Er içi antioksidan enzim olarak süperoksit dismutase (SOD) ve lipid peroksidasyon ürünü (ROS) malonyldialdehid (MDA) ölçüldü. İdrarla atılan glukoz (UG), albumin (UAE) ve N-acetyl-B-D glukozaminidase (NAG) incelendi. Böbrek dokusu ışık mikroskobunda ve immunohistokimyasal Tip IV kollajen birikimi incelendi. STZileglukoz, HbAlc, UG, UAE, NAG(P<000), üre, pKr (P<.005) artışı ile DN oluştu. HK grubuna göre, EN grubunda UG (P<.000), NAG, idrar volümü ve PO4 düşük (P<.05), Albyüksek (P<.05) veLKgrubunda Er, Hb yüksek, UG, NAG ve idrar volümü düşük (P<.05) bulundu. SK'egöre MDA değeri HK grubunda anlamsız arttı, EN ve LK grubunda değişmedi. DN bulguları olan glomerüler ve tubuler bazal membranda kalınlaşma ve tip IVkollajen birikimiHK'da belirgin, EN'de orta, LKgrubunda hafif derecede bulundu. Bulgularımız, ACEi'ne benzer şekilde LK'in DN gelişimini azaltıcı etki yaptığını düşündürmektedir.
FULL TEXT (PDF): 

REFERENCES

References: 

1. Parving H-H, Qsterby R, Ritz E. Diabetic Nephropathy. In
Brenner BM (editor). The kidney, 6th edn. Philadelphia: WB Saunders; 2000. pp. 1731-73
2. Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T: Diabetic Nephropathy in Type 1 (Insulin-dependent diabetes: An epidemiological study. Diabetologia 1983; 25: 496-501
3. Horie K, Miyata T, Maeda K, et al. Immunohistochemical
colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. J Clin Invest 1997; 100: 2995-3004
4. Hashimoto Y, Ideura T, Yoshimura A, Koshikawa S. Autoregulation of renal blood flow in streptozocin-induced
diabetic rats. Diabetes 1989; 38: 1109-13
5. Mclennan SV, Fisher E, Marthell SY, et al. Effects of
glucose on matrix metalloproteinase and plasmin activities in mesangial cells: Possible role in diabetic nephropathy. Kidney Int 2000; 58 (77): S-80-S-87
6. Catherwood MA, Powell LA, Anderson P, McMaster D,
Sharpe PC, Trimble E. Glucose-induced oxidative stress in mesangial cells. Kidney Int 2002; 61: 599-608
7. Leehey DJ, Singh AK, Alavi N, Singh R. Role of
anjiotensin II in diabetic nephropathy. Kidney Int 2000; 58 (77): S-93-S-98
8. Tang Z, Shou I, Wang LN, Fukui M, Tomino Y. Effects of
antihypertensive drugs or glycemic control on antioxidant enzyme activities in spontaneously hypertensive rats with
diabetes. Nephron 1997; 76: 323-30
9. Massry SG, Smogorzewski M. Role of elevated cystosolic calcium in the pathogenesis of complications in diabetes
mellitus. Miner Electrolyte Metab 1997; 23: 253-60
10. Tahiliani AG, McNeill JH. Diabetes-induced abnormalities in the myocardium. Life Sci 1986; 38: 959¬74
11. Piepper GM, Murray WJ. In vivo and in vitro intervention with L-Camitine prevents abnormal energy metabolism in isolated diabetic rat heart: chemical and phosphorous-31
NMR evidence. Biochim Med Metabol Biol 1987; 38;
111-20
12. Arduini A, Tyurin V, Tyuruna Y, Martelli EA, Molajoni F, Federici G. Acyl-traficking in membrane phospolipid fatty acid from the acyl-L-carnitjne pool to membrane phospholipids in intact human erythrocytes in hemodialysis patients. Biochem Biophys Res Commun 1992; 187: 353-358
13.
Şe
n S, Yüksel M, Üstündağ S. Diyaliz hastalarında eritropoietin ve L-karnitin tedavisinin anemi, eritrosit yaşam ve osmotik frajilkeye etkisi. Türk Nefrol Diyal
Transplant 2001; 10: 109-14
14. Arduini A. Carnitine and its acetyl esters as secondary antioxidants? Am Heart J 1992; 123: 1726-27
15. Miralles JM, Velasco J, Villabona V, Sanchez-Bemal C, Perez N, Corrales JJ, Garcia Diez LC, Villar E. Prospective study of the enzymatic activities in urine of N-acetyl-beta-D-glucosidases, alpha and beta-Dglucosidases, alpha-L and beta-D-fructosidases, and beta-Dgalactosidase
in type I diabetes mellitus with early nephropathy.
Diabetes Complications 1993; 7:199-203
16. Messerli FH, Frohlich ED, Dreslinski GR, et al. Serum uric acid in essential hypertension: An indicator of renal vascular involvement. Ann Intern Med 1980; 93: 817-21
17. Vallon V, Richter K, Blantz RC, Thompson S, Osswald H. Glomerular Hyperfiltration in experimental diabetes mellitus: Potential role of tubular reabsorption. J Am Soc
Nephrol 1999; 100: 2569-76
18. Pedrinelli R. Microalbuminuria in essential hypertension. A marker of systemic vascular damage? Nephrol Dial
Transplant 1997; 12: 379-98
19. Parving H-H, Hovind P, Rossing K, Andersen S. Evolving strategies for renoprotection: diabetic nephropathy. Curr Opin Nephrol Hypertens2001; 10: 515-22
20. Adler SG, Kang S-W, Feld S, et al. Glomerular mRNAs in human type 1 diabetes: Biochemical evidence for microalbuminuria as a manifestation of diabetic nephropathy. Kidney Int 2001; 60: 2330-36
21. Uchiyama-Tanaka Y, Matsubara H, Nozawa Y, et al. Anjiotensin II signaling and HB-EGF shedding via metalloproteinase in glomerular mesangial cells. Kidney Int 2001; 60: 2153-63
22. Schoonmaker GC, Fallet RW, Carmines PK. Superoxide anion curbs nitric oxide modulation of afferent arteriolar ANG II responsiveness in diabetes mellitus. Am J Physiol (Renal Physiol) 2000; 278: F302-F309
2 3. Onozato ML, Tojo A, Goto A, Fujita T, Wilcox CS. Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: Effects of ACEi and ARB. Kidney Int 2002; 61:186-94
24. Schnackenberg CG, Wilcox C. The SOD mimetic tempol restores vasodilation in affernt arterioles of experimental
diabetes. Kidney Int 2001; 59: 1859-64
2 5 . Craven PA, Derubertis FR, Kagan VB, Melhem M, Studer RK. Effects of supplementation with vitamin C or E on albuminuria, glomerular TGF-beta, and glomerular size in diabetes. J Am Soc Nephrol 1997; 8: 1405-14
26. Tamamoğullan N, Siliğ Y, Uçağasıoğlu S, Atalay A. Carnitine deficiency in diabetes mellitus complications. J
DiabCompl 1999;13:251-3
27. Terada R, Matsubara T, Koh N, Nakamura J, Hotta N.
Effects of propionyl-L-carnitine on cardiac dysfunction in streptozotocin-diabetic rats. Eur J Pharmacol 1998; 357: 185-91
28. Cameron NE, Cotter MA. Neurovascular effects of L-camitine treatment in diabetic rats. Eur J Pharmacol 1997; 319:239-244
29. Rodrigues B, Xiang H, McNeill JH. Effect of L-Carnitine
treatment on lipid metabolism and cardiac performance in chronically diabetic rats. Diabetes 1998; 37: 1358-64

Thank you for copying data from http://www.arastirmax.com