Journal of Molecular Histology

, Volume 43, Issue 5, pp 603–613 | Cite as

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in kidney of rats treated with gentamicin sulphate

  • Yildiray Kalkan
  • Kubra Asena Terim Kapakin
  • Adem Kara
  • Tennur Atabay
  • Ali KaradenizEmail author
  • Nejdet Simsek
  • Emre Karakus
  • Ismail Can
  • Serap Yildirim
  • Seckin Ozkanlar
  • Emin Sengul
Original Paper


The protective effects of Panax ginseng (PG) on gentamicin sulphate (GS) induced acute nephrotoxicity were investigated in rats. A total of 32 adult Sprague–Dawley rats were randomly divided into 4 equal groups and treated by intraperitoneous route for 10 days with: 0.5 mL of isotonic saline (group C), GS 100 mg/kg/day (group GS), co treatment PG (100 and 200 mg/kg/day) plus GS (100 mg/kg/day). After the last injection, kidney markers (urea, creatinine and blood urea nitrogen-BUN) and hepatic markers (aspartate aminotransferase-AST, alanine aminotransferase-ALT, gama glutamil transferase-GGT), and biochemical parameters were analyzed using diagnostic kits. Also, kidney changes were evaluated by immunohistochemical and stereological methods. GS treatment induced significant elevation (P < 0.05) in kidney and hepatic markers, most of biochemical parameters, and Bax immunoreactivity as well. However, co treatments with both doses of PG (100 and 200 mg/kg/day) significantly alleviated (P < 0.05) the GS-induced elevations and have partially protected rats from nephrotoxicity (reduction of kidney damage, and of urea, creatinine and BUN concentrations, and of apoptotic index). Both biochemical results and immunohistochemical evidence showed that administration of PG reduced the gentamicin-induced nephrotoxicity.


Panax ginseng Gentamicin sulphate Nephrotoxicity Apoptosis 


Conflict of interest

The authors declare that there are no conflicts of interest.


  1. Ajami M, Eghtesadi S, Pazoki-Toroudi H, Habibey R, Ebrahimi SA (2010) Effect of crocus sativus on gentamicin induced nephrotoxicity. Biol Res 43:83–90PubMedCrossRefGoogle Scholar
  2. Balakumara P, Ankur R, Arunachalam T (2010) Gentamicin-induced nephrotoxicity: do we have a promising therapeutic approach to blunt it? Pharmacol Res 62:179–186CrossRefGoogle Scholar
  3. Ben Ismail TH, Ali BH, Bashir AA (1994) Influence of iron, deferoxamine and ascorbic acid on gentamicin-induced nephrotoxicity in rats. Gen Pharmacol 25:1249–1252PubMedCrossRefGoogle Scholar
  4. Bledsoe G, Crickman S, Mao J, Xia CF, Murakami H, Chao L, Chao J (2006) Kallikrein/kinin protects against gentamicin-induced nephrotoxicity by inhibition of inflammation and apoptosis. Nephrol Dial Transplant 21:624–633PubMedCrossRefGoogle Scholar
  5. Chen XC, Chen Y, Zhu YG, Fang F, Chen LM (2002) Protective effect of ginsenoside Rg1 against MPTP-induced apoptosis in mouse substantia nigra neurons. Acta Pharmacol Sin 23:829–834PubMedGoogle Scholar
  6. Chen S, Liu J, Liu X, Fu Y, Zhang M, Lin Q, Zhu J, Mai L, Shan Z, Yu X, Yang M, Lin S (2011) Panax notoginseng saponins inhibit ischemia-induced apoptosis by activating PI3K/Akt pathway in cardiomyocytes. J Ethnopharmacol 137:263–270Google Scholar
  7. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91:231–241PubMedCrossRefGoogle Scholar
  8. Denamur S, Tyteca D, Marchand-Brynaert J, Van Bambeke F, Tulkens PM, Courtoy PJ, Mingeot-Leclercq MP (2011) Role of oxidative stress in lysosomal membrane permeabilization and apoptosis induced by gentamicin, an aminoglycoside antibiotic. Free Radic Biol Med 51:1656–1665PubMedCrossRefGoogle Scholar
  9. Dixit VR, Jain P, Bhandari K, Purohit AK (1991) Effects of ginseng (G-115) serum lipids of hyperlipidaemic rhesus monkeys (Macaca mulatta). Indian J Pharm Sci 53:88–91Google Scholar
  10. Erdem A, Gondogan NU, Usubatan A, Kilinc K, Erdem SR, Kara A (2000) The protective effect of taurine against gentamicin-induced acute tubular necrosis in rats. Nephrol Dial Transplant 15:1175–1182PubMedCrossRefGoogle Scholar
  11. Forge A, Schacht J (2000) Aminoglycoside antibiotics. Audiol Neurootol 5:3–22PubMedCrossRefGoogle Scholar
  12. Gross A, Mc Donnell JM, Korsmeyer SJ (1999) Bcl-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899–1911PubMedCrossRefGoogle Scholar
  13. Howard CV, Reed MG (1998) Unbiased Stereology: three dimensional measurement in microscopy. Bios Scientific Publishers, Oxford, pp 1–37Google Scholar
  14. Humes DH (1988) Aminoglycoside nephrotoxicity. Kidney Int 33:900–911PubMedCrossRefGoogle Scholar
  15. Hwang SY, Son DJ, Kim IW, Kim DM, Sohn SH, Lee JJ, Kim SK (2008) Korean red ginseng attenuates hypercholesterolemia-enhanced platelet aggregation through suppression of diacylglycerol liberation in high-cholesterol-diet-fed rabbits. Phytother Res 22:778–783PubMedCrossRefGoogle Scholar
  16. Jutila A, Rytomaa M, Kinnunen PK (1998) Detachment of cytochrome c by cationic drugs from membranes containing acidic phospholipids: comparison of lidocaine, propranolol, and gentamycin. Mol Pharmacol 54:722–732PubMedGoogle Scholar
  17. Karadeniz A, Yildirim A, Simsek N, Kalkan Y, Celebi F (2008) Spirulina platensis protects against gentamicin-induced nephrotoxicity in rats. Phytother Res 22:1506–1510PubMedCrossRefGoogle Scholar
  18. Karadeniz A, Cemek M, Simsek N (2009a) The effects of Panax ginseng and Spirulina platensis on hepatotoxicity induced by cadmium in rats. Ecotoxicol Environ Saf 72:231–235PubMedCrossRefGoogle Scholar
  19. Karadeniz A, Yıldırım A, Karakoç A, Kalkan Y, Çelebi F (2009b) Protective effect of Panax ginseng on carbon tetrachloride induced liver, heart and kidney injury in rats. Revue Med Vet 160:237–243Google Scholar
  20. Karahan I, Atessahin A, Yilmaz S, Ceribaşi AO, Sakin F (2005) Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats. Toxicology 215:198–204PubMedCrossRefGoogle Scholar
  21. Karakus E, Karadeniz A, Simsek N, Can I, Kara A, Yildirim S, Kalkan Y, Kisa F (2011) Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl4). J Hazard Mater 195:208–213Google Scholar
  22. Khan SA, Priyamvada S, Farooq N, Khan S, Khan MW, Yusufi AN (2009) Protective effect of green tea extract on gentamicin induced nephrotoxicity and oxidative damage in rat kidney. Pharmacol Res 59:254–262PubMedCrossRefGoogle Scholar
  23. Khan MR, Badar I, Siddiquah A (2011) Prevention of hepatorenal toxicity with Sonchus asper in gentamicin treated rats. BMC Complement Altern Med 11:113PubMedCrossRefGoogle Scholar
  24. Kim EH, Jang MH, Shin MC, Shin MS, Kim CJ (2003) Protective effect of aqueous extract of Ginseng radix against 1-methyl- 4-phenylpyridinium-induced apoptosis in PC12 cells. Biol Pharm Bull 26:1668–1673PubMedCrossRefGoogle Scholar
  25. Kitts DD, Hu C (2000) Efficacy and safety of ginseng. Public Health Nutr 3:473–485PubMedCrossRefGoogle Scholar
  26. Kotnis MS, Patel P, Menon SN, Sane RT (2004) Renoprotective effect of Hemidesmus indicus, a herbal drug used in gentamicin-induced renal toxicity. Nephrology (Carlton) 9:142–152Google Scholar
  27. Kwon BM, Kim MK, Baek NI, Kim DS, Park JD, Kim YK, Lee HK, Kim SI (1999) Acyl-CoA: cholesterol acyltransferase inhibitory activity of ginseng sapogenins, produced from the ginseng saponins. Bioorg Med Chem Lett 9:1375–1378PubMedCrossRefGoogle Scholar
  28. Lang H, Liu C (1997) Apoptosis and hair-cell degeneration in the vestibular sensory epithelia of the guinea pig following a gentamicin insult. Hear Res 111:177–184PubMedCrossRefGoogle Scholar
  29. Laurent G, Kishore BK, Tulkens PM (1990) Aminoglycoside-induced renal phospholipidosis and nephrotoxicity. Biochem Pharmacol 40:2383PubMedCrossRefGoogle Scholar
  30. Li J, Xie ZZ, Tang YB, Zhou JG, Guan YY (2011) Ginsenoside-Rd, a purified component from panax notoginseng saponins, prevents atherosclerosis in apoE knockout mice. Eur J Pharmacol 652:104–110PubMedCrossRefGoogle Scholar
  31. Lietz T, Brya J (1990) The effect of various aminoglycoside antibiotics on glycogen phosphorylase activity in liver and kidney medulla of rabbit. Acta Biochim Pol 37:187–190PubMedGoogle Scholar
  32. Liu Y, Zhang HG, Jia Y, Li XH (2010) Panax notoginseng saponins attenuate atherogenesis accelerated by zymosan in rabbits. Biol Pharm Bull 33:1324–1330PubMedCrossRefGoogle Scholar
  33. Martínez-Salgado C, Eleno N, Tavares P, Rodríguez-Barbero A, García-Criado J, Bolaños JP, López-Novoa JM (2002) Involvement of reactive oxygen species on gentamicin-induced mesangial cell activation. Kidney Int 62:1682–1692PubMedCrossRefGoogle Scholar
  34. Martínez-Salgado C, Eleno N, Morales AI, Pérez-Barriocanal F, Arévalo M, López-Novoa JM (2004) Gentamicin treatment induces simultaneous mesangial proliferation and apoptosis in rats. Kidney Int 65:2161–2171PubMedCrossRefGoogle Scholar
  35. Mattew TH (1992) Drug induced renal disease. Med J Australia 15:724–728Google Scholar
  36. Nakajima T, Hishida A, Kato A (1994) Mechanisms for protective effects of free radical scavengers on gentamicin-mediated nephropathy in rats. Am J Physiol 266:F425–F431PubMedGoogle Scholar
  37. Noorani AA, Gupta KA, Bhadada K, Kale MK (2011) Protective effect of methanolic leaf extract of caesalpinia Bonduc (L) on gentamicin-induced hepatotoxicity and nephrotoxicity in rats. IJPT 10:21–25Google Scholar
  38. Park WH, Lee SK, Kim CH (2005) A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats. Life Sci 76:1675–1690PubMedCrossRefGoogle Scholar
  39. Priuska EM, Clark K, Pecoraro V, Schacht J (1998) NMR spectra of iron-gentamicin complexes and the implications for aminoglycoside toxicity. Inorg Chim Acta 273:85–91CrossRefGoogle Scholar
  40. Qiang H, Zhang C, Shi ZB, Yang HQ, Wang KZ (2010) Protective effects and mechanism of Panax notoginseng saponins on oxidative stress-induced damage and apoptosis of rabbit bone marrow stromal cells. Chin J Integr Med 16:525–530Google Scholar
  41. Recknagel RO, Glender EA Jr, Britton RS (1991) Free radical damage and lipid peroxidation. In: Meeks RG (ed) Hepatotoxicology. CRC Press, Florida, pp 401–436Google Scholar
  42. Rouiller C (1969) General anatomy and histology of the kidney. The kidney, vol 1. Academic Press, New York, pp 61–156Google Scholar
  43. Saikumar P, Venkatachalam MA (2003) Role of apoptosis in hypoxic/ischemic damage in the kidney. Semin Nephrol 23:511–521PubMedCrossRefGoogle Scholar
  44. Servais H, Jossin Y, Van Bambeke F, Tulkens PM, Mingeot-Leclercq MP (2006) Gentamicin causes apoptosis at low concentrations in renal LLC-PK1 cells subjected to electroporation. Antimicrob Agents Chemother 50:1213–1221PubMedCrossRefGoogle Scholar
  45. Silan C, Uzun O, Comunoglu NU, Gokcen S, Bedirhan S, Cengiz M (2007) Gentamicin-induced nephrotoxicity in rats ameliorated and healing effects of resveratrol. Biol Pharm Bull 30:79–83PubMedCrossRefGoogle Scholar
  46. Song BB, Anderson DJ, Schacht J (1997) Protection from gentamicin ototoxicity by iron chelators in guinea pig in vivo. J Pharmacol Exp Ther 282:1–9Google Scholar
  47. Sterio DC (1984) The Unbiased estimation of number and size of arbitrary particles using the dissector. J Microsc 134:127–136PubMedCrossRefGoogle Scholar
  48. Vardi N, Parlakpinar H, Ozturk F, Acet A (2005) Gentamicininduced nephrotoxicity and protective effect of caffeic acid phenethyl ester in rats. Fundam Clin Pharmacol 19:173–177PubMedCrossRefGoogle Scholar
  49. Walker RJ, Duggin GG (1988) Drug nephrotoxicity. Annu Rev Pharmacol Toxicol 28:331–345PubMedCrossRefGoogle Scholar
  50. Wang X, Zheng YL, Li K, Lin N, Fan QX (2009) The effects of ginsenosides Rg3 on the expressions of VEGF and KDR in human lung squamous cancer cells. Zhong Yao Cai 32:1708–1710Google Scholar
  51. Weinberg JM, Humes HD (1980) Mechanisms of gentamicin-induced dysfunction of renal cortical mitochondria I effects on mitochondrial respiration. Arch Biochem Biophys 205:222–231PubMedCrossRefGoogle Scholar
  52. Xu L, Liu JT, Liu N, Lu PP, Pang XM (2011) Effects of Panax notoginseng saponins on proliferation and apoptosis of vascular smooth muscle cells. J Ethnopharmacol 137:226–230Google Scholar
  53. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275:1129–1132PubMedCrossRefGoogle Scholar
  54. Zhu LQ, Fan JP, Huang QF, Sun SL, Gao Y, Zou YH, Zhang Z, He LY, Zheng H (2003) Study on the anti-apopotosis induced by hypoxia/hypoglycemia and reoxygenation of panax notoginseng saponins in cultured rat hippocampal neurons. Zhongguo Zhong Yao Za Zhi 28:52–55 Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Yildiray Kalkan
    • 1
  • Kubra Asena Terim Kapakin
    • 2
  • Adem Kara
    • 3
  • Tennur Atabay
    • 4
  • Ali Karadeniz
    • 5
    Email author
  • Nejdet Simsek
    • 3
  • Emre Karakus
    • 6
  • Ismail Can
    • 3
  • Serap Yildirim
    • 7
  • Seckin Ozkanlar
    • 8
  • Emin Sengul
    • 5
  1. 1.Department of Histology and Embryology, Faculty of MedicineUniversity of RizeRizeTurkey
  2. 2.Department of Pathology, Faculty of Veterinary MedicineUniversity of AtatürkErzurumTurkey
  3. 3.Department of Histology and Embryology, Faculty of Veterinary MedicineUniversity of AtatürkErzurumTurkey
  4. 4.Bornova Veterinary Control and Research InstituteBornovaTurkey
  5. 5.Department of Physiology, Faculty of Veterinary MedicineUniversity of AtatürkErzurumTurkey
  6. 6.Department of Pharmacology and Toxicology, Faculty of Veterinary MedicineUniversity of AtatürkErzurumTurkey
  7. 7.Department of Physiology, Faculty of MedicineUniversity of AtatürkErzurumTurkey
  8. 8.Department of Biochemistry, Faculty of Veterinary MedicineUniversity of AtatürkErzurumTurkey

Personalised recommendations