Deneysel Diyabetik Ratlarda Ardıç (Juniperus communis L.) Yağının Nefropati Üzerine Etkileri

Hiperglisemi aracılı oksidatif stres diyabetik nefropatinin (DN) patogenezinde önemli bir rol oynar. Bu çalışmada, streptozotosin (STZ) ile indüklenmiş diyabetik ratlarda ardıç (Juniper berry; JB) yağının renoprotektif etkisinin araştırılması amaçlandı. Bu amaçla, 40 adet erkek Wistar albino rat rastgele seçilerek; kontrol, diyabetes mellitus (DM), DM+akarboz, DM+ardıç yağı ve ardıç yağı olmak üzere beş gruba ayrıldı. Deneysel diyabet, tek dozluk (55 mg/kg, periton içi [i.p]) STZ enjeksiyonu ile oluşturuldu. DM+ardıç ve ardıç grubu ratların yemlerine 50 ml/kg JB yağı katılarak verildi. 28 günlük deneme süresi sonunda ratlar sakrifiye edilerek kan ve doku örnekleri alındı. Böbrek dokusunda histopatolojik değişiklikler, immunohistokimyasal olarak caspase-3 (Kaspaz-3) ekspresyonu, biyokimyasal olarak malondialdehit (MDA) ve glutasyon (GSH) konsantrasyonları ve katalaz aktiviteleri çalışıldı. Serumda ise üre ve kreatinin düzeyleri incelendi. DM grubu ratlarda, histopatolojik olarak tubulus epitel hücrelerinde dejenerasyon ve nekroz, glomerular yapıda bozulma gözlemlenirken, immunohistokimyasal olarak tubul epitel hücrelerinde caspase-3 immun reaktivitesi yüksek saptandı. Biyokimyasal olarak DM grubu ratların böbrek dokusunda, MDA konsantrasyonu kontrol grubuna göre anlamlı olarak yüksek ve GSH konsantrasyonu ve katalaz aktivitesi anlamlı olarak düşük bulundu. Ayrıca DM grubunda serum üre ve kreatinin konsantrasyonları kontrol grubundan anlamlı olarak yüksek bulundu. DM+ardıç grubu ratlarda ise, ardıç tedavisi sonucu histopatolojik değişikliklerin düzeldiği, caspase-3 immun reaktivitesinin azaldığı ve biyokimyasal parametrelerin iyileştiği tespit edildi. Sonuç olarak, ardıç yağının denysel diyabetik ratlarda böbreği koruyucu etkileri olduğu belirlendi.

Anahtar Kelimeler:

Ardıç yağı, Diyabetik nefropati, Caspase-3, Rat

Effects of Juniperus communis L. Oil on Nephropathy in Experimental Diabetic Rats

Hyperglycaemia-mediated oxidative stress plays an important role in the pathogenesis of diabetic nephropathy. The present study investigated the renoprotective effect of Juniper (Juniper berry; JB) oil in rats with streptozotocin (STZ)-induced diabetes. For this, 40 male Wistar albino rats were divided into five group, namely, control, diabetes mellitus (DM), DM+acarbose, DM + JB oil and JB oil groups. Experimental diabetes was established by injecting the rats with a single dose (55 mg/kg) of STZ intraperitoneally. The rats in the DM+ardıç oil and ardıç oil groups received 50 ml JB oil/kg diet. After 28 days, the rats were sacrificed and their blood and tissue samples were obtained. Histopathological changes, caspase-3 immunoexpression, malondialdehyde MDA and glutathione (GSH) concentration and catalase activities in the kidney tissues of the rats were examined. Moreover, serum urea and creatinine levels were examined. Histopathologically, the rats in the DM group showed degeneration and necrosis of tubular epithelial cells and destruction of glomerular structures. Immunohistochemically, these rats showed increased caspase-3 immunoreactivity in the tubular epithelial cells. Biochemically, MDA concentration was significantly higher in the kidney tissue of the rats in the DM group than that of the rats in the control group. GSH concentration and catalase activities were significantly lower in the kidney tissue of the rats in the DM group than that of the rats in the control group. Moreover, serum urea and creatinine levels were significantly higher in the rats in the DM group than those in the control group. The rats in the DM + JB oil group showed an improvement in STZ-induced histopathological changes. Moreover, these rats showed decreased caspase-3 immunoexpression in the kidney tissue and improved biochemical parameters. Thus, these results indicate that JB oil exerts protective effects in the kidneys of diabetic rats.

Keywords:

Juniper oil, Diabetic nephropathy, Caspase-3, Rat,

PDF

___

Allen DA, Harwood SM, Varagunam M, Raftery MJ, Yaqoob MM, 2003: High glucose-induced oxidative stress causes apoptosis in proximal tubular epithelial cells and is mediated by multiple caspases. FASEB J, 17(8), 908-910.
Benson L, 1962: Plant taxonomy, methods and principles. Ronald Press. New York, NY.
Beutler E, Duron O, Kelly BM, 1963: Improved method for the determination of blood glutathione. J Lab Clin Med, 61, 882-890.
Bhatti F, Mankhey RW, Asico L, Quinn MT, Welch WJ, Maric C, 2005: Mechanisms of antioxidant and prooxidant effects of a-lipoic acid in the diabetic and non-diabetic kidney. Kidney Int, 67(4), 1371–1380.
Brezniceanu ML, Liu F, Wei CC, Chénier I, Godin N, Zhang SL, Filep JG, Ingelfinger JR, Craven PA, DeRubertis FR, Kagan VE, Melhem M, Studer RK, 1997: Effects of supplementation with vitamin C or E on albuminuria, glomerular TGF-beta, and glomerular size in diabetes. J Am Soc Nephrol, 8, 1405-1414.
Dalla VM, Saller A, Mauer M, Fioretto P, 2001: Role of mesangial expansion in the pathogenesis of diabetic nephropathy. J Nephrol, 14(4), 51–57.
Das J, Sil PC, 2012: Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats. Amino acids, 43(4), 1509-1523.
de Haan JB, Stefanovic N, Nikolic-Paterson D, Scurr LL, Croft KD, Mori TA, Hertzog P, Kola I, Atkins RC, Tesch GH, 2005: Kidney expression of glutathione peroxidase-1 is not protective against streptozotocin-induced diabetic nephropathy. Am J Physiol Renal Physiol, 289, 544-551.
Dormandy TL, 1980: Free radical reactions in biological systems. Ann R Coll Surg Engl, 62, 188-194.
Dunlop M, 2000: Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int, 77, 3-S12.
Filipowicz N, Kamiński M, Kurlenda J, Asztemborska M, Ochocka JR, 2003: Antibacterial and antifungal activity of juniper berry oil and its selected components. Phytother Res, 17(3), 227-231.
Fioretto P, Stehouwer CD, Mauer M, Chiesura-Corona M, Brocco E, Carraro A, Bortoloso E, van Hinsbergh VW, Crepaldi G, Nosadini R, 1998: Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure. Diabetologia, 41(2), 233–236.
Forbes JM, Coughlan MT, Cooper ME, 2008: Oxidative stress as amajor culprit in kidney disease in diabetes. Diabetes, 57, 1446–1454.
Freeman BA, Crapo JD,0 1981: Hyperoxia increases oxygen radical production in rat lung and lung mitochondria. J Biol Chem, 256, 10986-10992.
Ha H, Lee HB, 2000: Reactive oxygen species as glucose signaling molecules in mesangial cells cultured under high glucose. Kidney Int, 58(Suppl. 77), 19-25.
Harris DC, 2001: Tubulointerstitial renal disease. Curr Opin Nephrol Hypertens, 10, 303–313.
Huang THW, Peng G, Kota BP, Li GQ, Yamahara J, Roufogalis BD, Li Y, 2005: Anti-diabetic action of Punica granatum flower extract: activation of PPAR-c and identification of an active component. Toxicol Appl Pharmacol, 207, 160–169.
Kelly DJ, Stein-Oakley A, Zhang Y, Wassef L, Maguire J, Koji T, Thomson N, Wilkinson-Berka JL, Gilbert RE, 2004: Fas-induced apoptosis is a feature of progressive diabetic nephropathy in transgenic (mRen-2)27 rats: attenuation with renin-angiotensin blockade. Nephrology (Carlton), 9, 7-13.
Kikkawa R, Koya D, Haneda M, 2003: Progression of diabetic nephropathy. Am. J. Kidney Dis, 41(3), 19–21.
Kumar D, Robertson S, Burns KD, 2004: Evidence of apoptosis in human diabetic kidney. Mol Cell Biochem, 259, 67-70.
Lalenti S, Moncada M, Rosa D, 1993: Modulation of adjuvant arthritis by endogenous nitric oxide. Brit J Pharmacol, 110, 701- 706.
Larkins RG, Dunlop ME, 1992: The link between hyperglycaemia and diabetic nephropathy. Diabetologia, 35, 499–504.
Lartillot S, Kedziora P, Athias A, 1988: Purification and characterization of a new fungal catalase. Prep Biochem, 18(3), 241-246.
Ledwozyw A, Michalak J, Stepień A, Kadziołka A, 1986: The relationship between plasma triglycerides, cholesterol, total lipids andl ipid peroxidation products during human atherosclerosis. Clin Chim Acta, 155(3), 275- 83.
Lee YM, Kim H, Hong EK, Kang BH, Kim SJ 2000: Water extract of 1:1 mixture of Phellodendron cortex and Aralia cortex has inhibitory effects on oxidative stress in kidney of diabetic rats. J Ethnopharmacol, 73, 429–36.
Lewis JB, 1999: Diabetic nephropathy in patients with type II diabetes. Geriatr Nephrol Urol, 9(3), 167–175.
Li J, Qu X, Bertram JF, 2009: Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice. Am J Pathol, 175(4), 1380-1388.
Liu G, Sun Y, Li Z, Song T, Wang H, Zhang Y, Ge Z, 2008: Apoptosis induced by endoplasmic reticulum stress involved in diabetic kidney disease. Biochem Biophys Res Commun, 370(4), 651-656.
Madhuri K, Naik PR, 2017: Modulatory effect of garcinol in streptozotocin-induced diabetic Wistar rats. Arch Physiol Biochem, 123(5), 322-329.
Manna P, Sinha M, Sil PC, 2008: Amelioration of cadmium-induced cardiac impairment by taurine. Chem Biol Interact, 174, 88-97.
Matough FA, Budin SB, Hamid ZA, Alwahaibi N, Mohamed J, 2012: The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ Med J, 12(1), 5.
Mauer SM, Steffes MW, Ellis EN, Sutherland DE, Brown DM, Goetz FC, 1984: Structural-functional relationships in diabetic nephropathy. J Clin Invest, 74, 1143-1155.
Motshakeri M, Ebrahimi M, Goh YM, Othman HH, Hair-Bejo M, Mohamed S, 2014: Effects of brown seaweed (Sargassum polycystum) extracts on kidney, liver, and pancreas of type 2 diabetic rat model. J Evid Based Complementary Altern Med. Article ID 379407.
Nicolle E, Souard F, Faure P, Boumendjel A, 2011: Flavonoids as promising lead compounds in type 2 diabetes mellitus: molecules of interest and structure activity relationship. Curr Med Chem, 18(17), 2661-2672.
Obrosova IG, Fathallah L, Liu E, Nourooz-Zadeh J, 2003: Early oxidative stress in diabetic kidney: effect of DL-a-lipoic acid. Free Radic Biol Med, 34, 186-95.
Ochacka Jr, Asztemborska M, Zook, Dr, Sybılska D, Perez G, Ossıcını L, 1996: Enantiomers of monoterpenic hydrocarbons in essential oil from Juniperus communis. Phytochemistry, 44, 869-873.
Palsamy P, Subramanian S, 2011: Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1 signaling. Biochim Biophys Acta, 1812, 719-731.
Rajarajeswari N, Pari L, 2011: Antioxidant role of coumarin on streptozotocin-nicotinamide-induced type 2 diabetic rats. J Biochem Mol Toxicol, 25, 355-361.
Reutens AT, 2013: Epidemiology of diabetic kidney disease. Med Clin North Am, 97, 1-18.
Rossing P, Rossing K, Jacobsen P, Parving HH, 1995: Unchanged incidence of diabetic nephropathy in IDDM patients. Diabetes, 44(7), 739–743
Sakulnarmrat K, Konczak I, 2012: Composition of native Australian herbs polyphenolic-rich fractions and in vitro inhibitory activities against key enzymes relevant to metabolic syndrome. Food Chem, 134(2), 1011-1019.
Sellamuthu PS, Arulselvan P, Muniappan BP, Fakurazi S, Kandasamy M, 2013: Mangiferin from Salacia chinensis prevents oxidative stress and protects pancreatic β-cells in streptozotocin-induced diabetic rats. J Med Food, 16(8), 719-727.
Shahidi F, Wanasundara PK, Wanasundara PD, 1992: Phenolic antioxidants. Crit Rev Food Sci Nutr, 32, 67-103.
Sheela N, Jose MA, Sathyamurthy D, Kumar BN, 2013: Effect of silymarin on streptozotocin-nicotinamide-induced type 2 diabetic nephropathy in rats. Iran J Kidney Dis, 7, 117-123.
Subash-Babu P, Alshatwi AA, Ignacimuthu S, 2014: Beneficial antioxidative and antiperoxidative effect of cinnamaldehyde protect streptozotocin-induced pancreatic beta-cells damage in wistar rats. Biomol Ther (Seoul), 22(1), 47-54.
Tan AL, Forbes JM, Cooper ME, 2007: AGE, RAGE, and ROS in diabetic nephropathy. Semin Nephrol, 27(2), 130-143.
Uyar A, Yaman T, Keles OF, Alkan EE, Celik I, Yener Z, 2017: Protective effects of Bryonia multiflora extract on pancreatic beta cells, liver and kidney of streptozotocin-induced diabetic rats: histopathological and immunohistochemical investigations. Indian J Pharm Educ Res, 51(3), Suppl:S403-11.
Wagener FADTG, Dekker D, Berden JH, Scharstuhl A, Van der Vlag J, 2009: The role of reactive oxygen species in apoptosis of the diabetic kidney. Apoptosis, 14(12), 1451-1458.
Winiarska K, Szymanski K, Gorniak P, Dudziak M, Bryla J, 2009: Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits. Biochimie, 91, 261-270.
Yaman T, Uyar A, Celik I, Alkan EE, Keles OF, Yener Z, 2017: Histopathological and immunohistochemical study of antidiabetic effects of Heracleum persicum extract in experimentally diabetic rats. IJPER, 51(3), 450-457.
Yaman T, Yener Z, Celik I, 2016: Histopathological and biochemical investigations of protective role of honey in rats with experimental aflatoxicosis. BMC Complement Altern Med, 16(1), 232.
Yeşilbağ D, Cengiz SS, Cetin I, Meral Y, Biricik H, 2014: Influence of juniper (Juniperus communis) oil on growth performance and meat quality as a natural antioxidant in quail diets. Br Poult Sci, 55(4), 495-500.