D-Galaktoz ile İndüklenen Farelerde Yaşlanma Modelinin Nefropatisi Üzerine Mirisitrin ve Vitamin E’nin Koruyucu Etkileri

Abstract

Amaç: Fizyolojik koşullarda oksidatif strese bağlı olarak hücre ve dokularda yaşlanma meydana gelir. D-galaktoz (DG), hayvan çalışmalarında yaşlanmaya neden olmak için yaygın olarak kullanılmaktadır. Bu çalışmada, DG ile indüklenen farelerde yaşlanma modelinde mirisitrin ve vitamin E’nin renal koruyucu etkileri değerlendirildi. Gereç ve Yöntemler: Yaşlanma modelinin uyarılması için subkutan DG enjeksiyonu uygulandı. 72 dişi fare rastgele şekilde altı gruba ayrıldı: Tüm gruplara altı hafta boyunca 500 mg/kg/gün DG verildi. Uygulamanın son 28 günü mirisitrin ile tedavi edilen gruplara subkutan olarak 5, 10 ve 20 mg/kg/gün, E vitamini grubuna ise gavaj yoluyla 100 mg/kg/gün uygulandı. İdrar ve plazma albümini, BUN, kreatinin seviyeleri, MDA, TAC ile böbrek histolojik değişiklikleri değerlendirildi. Bulgular: Kontrol grubu ile karşılaştırıldığında, DG grubunda plazma albumin düzeyi önemli ölçüde azalırken (p=0.001), idrar albümini (p=0.001), BUN (p<0.001) ve kreatinin (p=0.010) düzeylerinde anlamlı bir artış gözlendi. Ayrıca MDA düzeylerinde anlamlı artış (p=0.002) ile birlikte TAC’de de anlamlı düşüş (p=0.012) gözlendi. Kontrol ile karşılaştırıldığında, eritrosit konjesyonu (p<0.001), inflamatuar hücrelerin infiltrasyonu (p<0.001) ve proksimal tübül hücre hasarı (p=0.004) gibi histopatolojik değişiklikler önemli ölçüde artarken, glomerül çapı önemli ölçüde azaldı (p=0.038). Mirisitrin ve E vitamininin uygulanması, çalışılan tüm değişkenler üzerinde önemli bir iyileştirici etki göstermiştir. Sonuç: Mirisitrinin DG’nin neden olduğu böbrek hasarı üzerindeki iyileştirme etkileri yaklaşık olarak E vitaminine eşdeğer idi. Mirisitrin ve E vitamini, yaşlanma modelinin nefropatisi üzerinde faydalı etkilere sahip olabilir.

Keywords

• Yaşlanma
• D-galaktoz
• Nefropati
• Fareler
• Myrisitrin

Protective Effects of Myricitrin and Vitamin E on Nephropathy of Aging Mice Model Induced By D-Galactose

Abstract

Aim: Aging occurs in cells and tissues due to oxidative stress in physiological conditions. D-galactose (DG) is widely used to cause aging in animal studies. In this study, the renal protective effects of myricitrin and vitamin E in the aging mice model induced by DG was evaluated. Material and Methods: Subcutaneous DG injection was used for induction of the aging model. 72 female mice were randomly divided into six groups: All groups were received DG at 500 mg/kg/d for six weeks. In the last 28 days, the groups treated with myricitrin subcutaneously received 5, 10, and 20 mg/kg/d, and the vitamin E group received 100 mg/kg/d by gavage. Urine and plasma albumin, BUN, creatinine levels, MDA, TAC, and kidney histological changes were evaluated. Results: Plasma albumin was significantly decreased (p=0.001), but a significant increase in urine albumin (p=0.001), BUN (p<0.001), and creatinine (p=0.010) levels was observed in the DG group when compared with the control. Also, a significant increase in MDA levels (p=0.002) along with a significant decrease in TAC (p=0.012) was observed. Histopathological changes such as congestion of erythrocytes (p<0.001), infiltration of inflammatory cells (p<0.001), and proximal tubule cell damage (p=0.004) significantly increased, while glomerulus diameter significantly decreased (p=0.038) in comparison to the control. Administration of myricitrin and vitamin E showed a significant ameliorative effect on all studied variables. Conclusion: The improvement effects of myricitrin on DG-induced kidney damage was approximately equivalent to vitamin E. Myricitrin and vitamin E could have beneficial effects on the nephropathy of aging model.

Keywords

• Aging
• D-galactose
• Nephropathy
• Mice
• Myricitrin

References

1. Diamanti-Kandarakis E, Dattilo M, Macut D, Duntas L, Gonos ES, Goulis DG, et al. MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview. Eur J Endocrinol. 2017;176(6):R283-308.
2. Peter JS, Shalini M, Giridharan R, Basha KS, Lavinya UB, Evan Prince S. Administration of coenzyme Q10 to a diabetic rat model: changes in biochemical, antioxidant, and histopathological indicators. Int J Diabetes Dev Ctries. 2020;40(1):143-52.
3. Ahangarpour A, Ramezani-Aliakbari F. Protective effects of Olea europaea fruit extracts on metabolic disorders associated with sucrose-induced metabolic syndrome in rats. Avicenna J Med Biochem. 2018;6(1):8-14.
4. Ahangarpour A, Alboghobeish S, Rezaei M, Khodayar MJ, Oroojan AA, Zainvand M. Evaluation of diabetogenic mechanism of high fat diet in combination with Arsenic exposure in male mice. Iran J Pharm Res. 2018;17(1):164-83.
5. Karaçor K, Çam M, Orhan N, Coşgun E, Demirin H. High fatty diet effects on rat liver. Eur J Gen Med. 2014;11(2):99-108.
6. Huang CC, Chiang WD, Huang WC, Huang CY, Hsu MC, Lin WT. Hepatoprotective effects of swimming exercise against D-galactose-induced senescence rat model. Evidence-Based Complement Alternat Med. 2013;2013:275431.
7. Hakimizadeh E, Hassanshahi J, Kaeidi A, Nematollahi MH, Taghipour Z, Rahmani M, et al. Ceftriaxone improves hepatorenal damages in mice subjected to D-galactose-induced aging. Life Sci. 2020;258:118119.
8. Xu Y, Zhang J, Liu J, Li S, Li C, Wang W, et al. Luteolin attenuate the D-galactose-induced renal damage by attenuation of oxidative stress and inflammation. Nat Prod Res. 2015;29(11):1078-82.

9. de Oliveira MC, Schoffen JPF. Oxidative stress action in cellular aging. Braz Arch Biol Technol. 2010;53(6):1333-42.
10. Aloud AA, Veeramani C, Govindasamy C, Alsaif MA, El Newehy AS, Al-Numair KS. Galangin, a dietary flavonoid, improves antioxidant status and reduces hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats. Redox Rep. 2017;22(6):290-300.
11. Xiang D, Wang CG, Wang WQ, Shi CY, Xiong W, Wang MD, et al. Gastrointestinal stability of dihydromyricetin, myricetin, and myricitrin: an in vitro investigation. Int J Food Sci Nutr. 2017;68(6):704-11.
12. Zhang B, Shen Q, Chen Y, Pan R, Kuang S, Liu G, et al. Myricitrin alleviates oxidative stress-induced inflammation and apoptosis and protects mice against diabetic cardiomyopathy. Sci Rep. 2017;7:44239.
13. Dua TK, Joardar S, Chakraborty P, Bhowmick S, Saha A, De Feo V, et al. Myricitrin, a glycosyloxyflavone in Myrica esculenta bark ameliorates diabetic nephropathy via improving glycemic status, reducing oxidative stress, and suppressing inflammation. Molecules. 2021;26(2):258.
14. Kongkham S, Sriwong S, Tasanarong A. Protective effect of alpha tocopherol on contrast-induced nephropathy in rats. Nefrologia. 2013;33(1):116-23.
15. Omidi M, Ahangarpour A, Mard SA, Khorsandi L. The effects of myricitrin and vitamin E against reproductive changes induced by D-galactose as an aging model in female mice: An experimental study. Int J Reprod Biomed. 2019;17(11):789-98.
16. Mojadami S, Ahangarpour A, Mard SA, Khorsandi L. Diabetic nephropathy induced by methylglyoxal: gallic acid regulates kidney microRNAs and glyoxalase1-Nrf2 in male mice. Arch Physiol Biochem. 2021;[Epub ahead of print]. doi: 10.1080/13813455.2020.1857775.
17. Ho SC, Liu JH, Wu RY. Establishment of the mimetic aging effect in mice caused by D-galactose. Biogerontology. 2003;4(1):15-8.
18. Amraoui W, Adjabi N, Bououza F, Boumendjel M, Taibi F, Boumendjel A, et al. Modulatory role of selenium and vitamin E, natural antioxidants, against bisphenol A-induced oxidative stress in Wistar albinos rats. Toxicol Res. 2018;34(3):231-9.
19. Barnes P, Yeboah JK, Gbedema W, Saahene RO, Amoani B. Ameliorative effect of Vernonia amygdalina plant extract on heavy metal-induced liver and kidney dysfunction in rats. Adv Pharmacol Pharm Sci. 2020;2020:2976905.
20. Dunn SR, Qi Z, Bottinger EP, Breyer MD, Sharma K. Utility of endogenous creatinine clearance as a measure of renal function in mice. Kidney Int. 2004;65(5):1959-67.
21. Niu HS, Liu IM, Niu CS, Ku PM, Hsu CT, Cheng JT. Eucommia bark (Du-Zhong) improves diabetic nephropathy without altering blood glucose in type 1-like diabetic rats. Drug Des Devel Ther. 2016;10:971-8.
22. Karakose S. Serum uric acid level and cardiovascular disease development risk in stage 3-5 chronic kidney disease patients. Duzce Med J. 2020;22(3):171-4.
23. Ichii O, Nakamura T, Irie T, Otani Y, Hosotani M, Masum MA, et al. Age-related glomerular lesions with albuminuria in male cotton rats. Histochem Cell Biol. 2020;153(1):27-36.
24. Feng Y, Yu YH, Wang ST, Ren J, Camer D, Hua YZ, et al. Chlorogenic acid protects D-galactose-induced liver and kidney injury via antioxidation and anti-inflammation effects in mice. Pharm Biol. 2016;54(6):1027-34.
25. Abo-Elmaaty AMA, Behairy A, El-Naseery NI, Abdel-Daim MM. The protective efficacy of vitamin E and cod liver oil against cisplatin-induced acute kidney injury in rats. Environ Sci Pollut Res. 2020;27(35):44412-26.
26. Li R, Hu L, Hu C, Wang Q, Lei Y, Zhao B. Myricitrin protects against cisplatin-induced kidney injury by eliminating excessive reactive oxygen species. Int Urol Nephrol. 2020;52(1):187-96.
27. Yousefi M, Mohammadi S, Jalali M, Beheshti F. Effect of different doses of curcumin on sperm parameters and oxidative stress in testis of d-galactose induced aging mice model. J Babol Univ Med Sci. 2019;21(1):53-60.
28. Michelis R, Kristal B, Zeitun T, Shapiro G, Fridman Y, Geron R, et al. Albumin oxidation leads to neutrophil activation in vitro and inaccurate measurement of serum albumin in patients with diabetic nephropathy. Free Radic Biol Med. 2013;60:49-55.
29. Karakaş H, Eren MA, Koyuncu İ, Kırhan İ, Sabuncu T. The evaluation of SCUBE-1 and sCD40L levels in diabetic nephropathy. Duzce Med J. 2019;21(3):243-7.
30. Morales AI, Vicente-Sánchez C, Sandoval JM, Egido J, Mayoral P, Arévalo MA, et al. Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in rats is based on its antioxidant properties. Food Chem Toxicol. 2006;44(12):2092-100.
31. Li DD, Li WJ, Kong SZ, Li SD, Guo JQ, Guo MH, et al. Protective effects of collagen polypeptide from tilapia skin against injuries to the liver and kidneys of mice induced by d-galactose. Biomed Pharmacother. 2019;117:109204.
32. Gadi R, Samaha FF. Dyslipidemia in type 2 diabetes mellitus. Curr Diab Rep. 2007;7(3):228-34.
33. Pandhare R, Sangameswaran B. Extract of Adenanthera pavonina L. seed reduces development of diabetic nephropathy in streptozotocin-induced diabetic rats. Avicenna J Phytomed. 2012;2(4):233-42.
34. Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E. Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007;2007:45673.
35. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126-67.
36. John S, Kale M, Rathore N, Bhatnagar D. Protective effect of vitamin E in dimethoate and malathion induced oxidative stress in rat erythrocytes. J Nutr Biochem. 2001;12(9):500-4.