Influence of Polyalthia longifolia (Sonn) leaves on oxidative stress biomarkers in the kidney of cadmium-induced toxicity rats

  • Ajibade O. OyeyemiEmail author
  • Olatunde A. Oseni
  • Olorunfemi R. Molehin
  • Adebimpe O. Babatunde
Original Article


Polyalthia longifolia (Sonn.) (False ashoka) is well-known in traditional system of medicine for its medicinal and therapeutic uses. However, the ameliorative effect of this plant against cadmium-induced oxidative stress in rat model has not been reported. Hence, this preliminary study investigates the prophylactic and the curative effects of aqueous and methanolic leaf extracts of Polyalthia longifolia against cadmium-induced nephrotoxicity in rats. Animals in group I served as control and administered distilled water only; group II was administered cadmium (4 mg/kg/body weight) every other day for 14 days; rats of groups III and IV served as the prophylactic group and were pre-treated with P. longifolia aqueous and methanolic leaf extract for 7 days and then exposed to cadmium for 7 days; and groups V, VI, VII, and VIII served as curative groups and were firstly exposed to cadmium for 7 days and then post-treated with 100 mg and 200 mg/kg body weight of aqueous extract and 100 mg and 200 mg/kg body weight of methanolic extract P. longifolia for another 7 days. Cd intoxication significantly (p < 0.05) increased the activities of serum creatinine and C-reactive protein levels. Cd exposure caused a significant increase (p < 0.05) in tissue total cholesterol and triglyceride levels. The levels of renal antioxidant parameters: glutathione-s-transferase, superoxide dismutase, catalase, glutathione reductase, and reduced glutathione, were significantly (p < 0.05) decreased in Cd-intoxicated rats with concomitant elevation of lipid peroxidation. Histopathological examination confirms the biochemical findings. Pre- and post-treatment with P. longifolia restored antioxidant status, improved lipid profiles, and attenuated the lesions in the tissues. Both extracts of P. longifolia protects against Cd-induced kidney toxicities via antioxidant activities.


Polyalthia longifolia Cadmium Nephrotoxicity Oxidative stress Antioxidant Histopathology 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All institutional and national standards for the care and use of laboratory animals were followed. This article does not contain any studies with human participants performed by any of the authors.


  1. Adam-Vizi V, Seregi M (1982) Receptor dependent stimulatory effect of noradrenaline on Na+/K+ ATPase in rat brain homogenate: role of lipid peroxidation. Biochem Pharmacol 31:2231–2236PubMedCrossRefGoogle Scholar
  2. Adaramoye OA, Akanni OO (2016) Modulatory effects of methanol extract of Artocarpus altilis (Moraceae) on cadmium-induced hepatic and renal toxicity in male Wistar rats. Pathophysiol 23:1–9CrossRefGoogle Scholar
  3. Adesanoye OA, Adekunle AE, Adewale OB, Mbagwu AE, Delima AA, Adefegha SA, Molehin OR, Farombi EO (2016) Chemoprotective effect of Vernonia amygdalina Del. (Astereacea) against 2-acetylaminofluorene-induced hepatotoxicity in rats. Toxicol Ind Health 32(1):47–58PubMedCrossRefPubMedCentralGoogle Scholar
  4. Asru KS (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394CrossRefGoogle Scholar
  5. Bulat Z, Đukić-Ćosić D, Antonijevic B, Bulat P, Vujanovic D, Buha A, Matović V (2012) Effect of magnesium supplementation on the distribution patterns of zinc, copper, and magnesium in rabbits exposed to prolonged cadmium intoxication. The Scientific World J 2012:572514. CrossRefGoogle Scholar
  6. Bulat Z, Dukic-Cosic D, Antonijevic B, Buha A, Bulat P, Pavlovic Z, Matovic V (2017) Can zinc supplementation ameliorate cadmium-induced alterations in the bioelement content in rabbits? Arh Hig Rada Toksikol 68:38–45PubMedCrossRefPubMedCentralGoogle Scholar
  7. Cuypers A, Plusquin M, Remans T, Jozefczak M (2010) Cadmium stress: an oxidative challenge. BioMetals 23(5):927–940PubMedCrossRefPubMedCentralGoogle Scholar
  8. David CW, Lau, Dhillon B, Yan H, Szmitko PE, Adipokines VS (2005) Molecular links between obesity and atheroslcerosis. Am J Physiol Heart Circ Physiol 288:H2031–H2041CrossRefGoogle Scholar
  9. Disbrey BD, Rack JH (1970) Book of histological laboratory methods. Harcourt Brace/ChurchillLivingstone, LondonGoogle Scholar
  10. Ekor M (2013) The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 4:177–180Google Scholar
  11. Elliott AJ, Scheiber SA, Thomas C, Pardini RS (1992) Inhibition of glutathione reductase by flavonoids. A structure activity study. Biochem Pharmacol:1603–1608PubMedCrossRefPubMedCentralGoogle Scholar
  12. Eneman JD, Potts RJ, Osier M, Shukla GS, Lee CH, Chin JF (2000) Suppressed oxidant-induced apoptosis in cadmium adapted alveolar epithelial cells and its potential involvement in cadmium carcinogenesis. Toxicol 147:215–228CrossRefGoogle Scholar
  13. El-Maraghy SA, Gad MZ, Fahim AT, Hamdy MA (2001) Effect of cadmium and aluminum intake on the antioxidant status and lipid peroxidation in rat tissues. J Biochem Mol Toxicol 15(4):207–214PubMedCrossRefPubMedCentralGoogle Scholar
  14. El-Sayed YS, El-Neweshy MS (2009) Impact of lead toxicity on male rat reproduction at hormonal and histopathological levels. Toxicol Lett 189:S219–S220CrossRefGoogle Scholar
  15. Farooq T (2009) Phytochemical and pharmacological investigation of the leaves of Carica papaya Linn. East West University, Dhaka, pp 26–37Google Scholar
  16. Faizi S, Khan RA, Azher S, Khan SA, Tauseef S, Ahmad A (2003) New antimicrobial alkaloids from the roots of Polyalthia longifolia var. pendula. Planta Med 69:350–355PubMedCrossRefPubMedCentralGoogle Scholar
  17. Flora S, Flora G, Saxena G (2006) Environmental occurrence, health effects and management of lead poisoning. In: Casas JS, Sordo J (eds) Lead: chemistry, analytical aspects, environmental impact and health effects. Elsevier Science, Amsterdam, pp 158–228CrossRefGoogle Scholar
  18. Halliwell B, Gutteridge JMC (1999) In: Sies H (ed) Free radicals in biology and medicine, vol 1999. Oxford University Press, New York, pp 617–783Google Scholar
  19. Jarup L, Hellstrom L, Alfven T, Carlsson MD, Grubb A, Persson B (2000) Low level exposure to cadmium and early kidney damage. The OSCAR study Occup Environ Med 57(668):72Google Scholar
  20. Jurczuk M, Brzoska MM, Moniuszko-Jakoniu J, Galazyn-Sidorczuk M, Kulikowska-Karpinska E (2004) Antioxidant enzymes activity and lipid peroxidationin liver and kidney of rats exposed to cadmium and ethanol. Food Chem Toxicol 42:429–438PubMedCrossRefPubMedCentralGoogle Scholar
  21. Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR (1974) Bromobenzene induced liver necrosis: protective role of glutathione and evidence for 3,4 bromobenzene oxide as the hepatotoxic metabolite. Pharmacol 11:151–169CrossRefGoogle Scholar
  22. Kara H, Karatas F, Canatan H, Servi K (2005) Effects of exogenous metallothionein on acute cadmium toxicity in rats. Biol Trace Elem Res 104(3):223–232PubMedCrossRefPubMedCentralGoogle Scholar
  23. Katkar KV, Suthar AC, Chauhan VS (2010) The chemistry, pharmacologic, and therapeutic applications of Polyalthia longifolia. Pharm Rev 4(7):62–68CrossRefGoogle Scholar
  24. Kayama F, Yoshida T, Elwell MR, Luster MI (1995) Role of tumor necrosis factor- _in cadmium-induced hepatotoxicity. Toxicol Appl Pharmacol 131:224–223PubMedCrossRefPubMedCentralGoogle Scholar
  25. Kirtikar KR, Basu BD (1995) Indian Medicinal Plants, vol 1. International Book Distributors, Uttarakhand, p 562Google Scholar
  26. Sashidhara KV, Singh SP, Srivastava A, Puri A (2011) Identification of the antioxidant principles of Polyalthia longifolia var. pendula using TEAC assay. Nat Prod Res 25(9):918–926PubMedCrossRefPubMedCentralGoogle Scholar
  27. Lawerence RA, Burk RF (1961) Glutathione peroxidase activity in selenium-deficient rats liver. Biochem Biophys Res Commun 71:952–958CrossRefGoogle Scholar
  28. Liu D, Yang J, Wang L (2013) Cadmium induces ultra-structural changes in the hepatopancreas of the freshwater crab Sinopotamon henanense. Micron 47:24–32PubMedCrossRefPubMedCentralGoogle Scholar
  29. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  30. Luparello C, Sirchia R, Longo A (2011) Cadmium as a transcriptional modulator in human cells. Crit Rev Toxicol 41(1):75–82PubMedCrossRefGoogle Scholar
  31. Malairajan P, Gopalakrishnan G, Narasimhan S, Veni KJ (2008) Evalution of anti-ulcer activity of Polyalthia longifolia (Sonn.) Thwaites in experimental animals. Indian J Pharmacol 40(3):126–128Google Scholar
  32. Martínez-Paz P, Morales M, Martín R, Martínez-Guitarte JL, Morcillo G (2014) Characterization of the small heat shock protein Hsp27 gene in Chironomusriparius (Diptera) and its expression profile in response to temperature changes and xenobiotic exposures. Cell Stress Chaperones 19:529–540PubMedCrossRefGoogle Scholar
  33. Matés JM (2000) Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicology 153(1–3):83–104PubMedCrossRefGoogle Scholar
  34. Misra HP, Fridovich I (1972) The generation of superoxide radical during the antioxidant of hemoglobin. J Biol Chem 247:6960–6962PubMedGoogle Scholar
  35. Molehin OR, Adeyanju AA, Adefegha AA, Akomolafe SF (2018) Protocatechuic acid mitigates adriamycin-induced reproductive toxicities and hepatocellular damage in rats. Comp Clin Pathol 27:1681–1689CrossRefGoogle Scholar
  36. Murthy MM, Subramanyam M, Hima BM, Annapurna J (2005) Antimicrobial activity of clerodane diterpenoids from Polyalthia longifolia seeds. Fitoterapia 76(3–4):336–339PubMedCrossRefGoogle Scholar
  37. Nair R, Chanda S (2006) Evaluation of polyalthia longifolia (sonn.) thw. leaf extracts for anti-fungal activity. J Cell Tissue Res 6(1):581–584Google Scholar
  38. Nair R, Shukla V, Chanda S (2007) Assessment of Polyalthia longifolia var. pendula for hypoglycemic and antihyperglycemic activity. J Clin Diagn Res 1:116–121Google Scholar
  39. Navaneethan D, Rasool M (2014) p-Coumaric acid, a common dietary polyphenol, protects cadmium chloride-induced nephrotoxicity in rats. Ren Fail 36:244–251PubMedCrossRefPubMedCentralGoogle Scholar
  40. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358PubMedPubMedCentralCrossRefGoogle Scholar
  41. Ojo OA, Ajiboye BO, Oyinloye BE, Ojo AB (2014) Prophylactic effects of ethanolic extract of Irvingia gabonensis stem bark against cadmium-induced toxicity in albino rats. Adv Pharm 10(1155)Google Scholar
  42. Onyema OO, Farombi EO, Emerole GO, Ukoha AI, Onyeze GO (2006) Effect of vitamin E on monosodium glutamate induced hepatotoxicity and oxidative stress in rats. Indian J Biochem Biophys 43:20–24PubMedPubMedCentralGoogle Scholar
  43. Orororo OC, Asagba SO, Tonukari NJ, Okandeji OJ, Mbanugo JJ (2018) Effects of Hibiscus Sabdarrifa L. anthocyanins on cadmium-induced oxidative stress in Wistar rats. J Appl Sci Environ Manag 22(4):465–470Google Scholar
  44. Pasceri VI, Willerson JT, Yeh ET (2000) Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 102(18):2165–2168PubMedCrossRefPubMedCentralGoogle Scholar
  45. Prabu SM, Muthumani M, Shagirtha K (2013) Quercetin potentially attenuates cadmium induced oxidative stress mediated cardiotoxicity and dyslipidemiain rats. Eur Rev Med. Pharmacol Sci 17:582–595Google Scholar
  46. Renuga-devi J, Prabu SM (2009) Naringenin protects against cadmium-induced oxidative renal dysfunction in rats. Toxicol 256:128–134CrossRefGoogle Scholar
  47. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH (1998) Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 98:731–733PubMedCrossRefPubMedCentralGoogle Scholar
  48. Roccheri M, Agnello M, Bonaventura R, Matranga V (2004) Cadmium induced the expression of specific stress proteins in sea urchin embryo. Biochem Biophys Res Commun 321:80PubMedCrossRefPubMedCentralGoogle Scholar
  49. Roopha PD, Padmalatha C (2004) Effect of herbal preparation on heavy metal (cadmium) induced antioxidant system in female Wistar rats. J Med Toxicol 8(2012):101–107Google Scholar
  50. Salinska A, Włostowski T, Ole’nska E (2013) Differential susceptibility to cadmium-induced liver and kidney injury in wild and laboratory-bred bank voles Myodes glareolus. Arch Environ Contam Toxicol 65:324–331PubMedPubMedCentralCrossRefGoogle Scholar
  51. Samuel JB, Stanley JA, Roopha DP, Vengatesh G, Anbalagan J, Banu SKMM, Aruldhas MM (2011) Lactational hexavalent chromium exposure-induced oxidative stress in rat uterus is associated with delayed puberty and impaired gonadotropin levels. Hum Exp Toxicol 30:91–101PubMedCrossRefPubMedCentralGoogle Scholar
  52. Schauder A, Avital A, Malik Z (2010) Regulation and Gene Expression of Heme Synthesis under heavy metal exposure. J Environ Pathol Toxicol Oncol 29(2):137–158PubMedCrossRefPubMedCentralGoogle Scholar
  53. Stohs SJ, Bagchi D, Hassoun E, Bagchi M (2000) Oxidative mechanisms in the toxicity of chromium and cadmium ions. J Environ Pathol Toxicol Oncol 20:77–88Google Scholar
  54. Tanna A, Nair R, Chanda S (2009) Assessment of anti-inflammatory and hepatoprotective potency of Polyalthia longifolia var. pendula leaf in wistar albino rats. J Nat Med 63:80–85PubMedCrossRefPubMedCentralGoogle Scholar
  55. Thévenod F (2010) Catch me if you can! Novel aspects of cadmium transport in mammalian cells. BioMetals 23(5):857–875PubMedCrossRefPubMedCentralGoogle Scholar
  56. Valko M, Morris H, Cronin MTD (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208PubMedCrossRefPubMedCentralGoogle Scholar
  57. Vesey DA (2010) Transport pathways for cadmium in the intestine and kidney proximal tubule: focus on the interaction with essential metals. Toxicol Lett 198(1):13–19PubMedCrossRefPubMedCentralGoogle Scholar
  58. Wallace DR, Spandidos DA, Tsatsakis A, Schweitzer A, Djordjevic V, Djordjevic AB (2019) Potential interaction of cadmium chloride with pancreatic mitochondria: implications for pancreatic cancer. Int J Mol Med 44(1):145–156PubMedPubMedCentralGoogle Scholar
  59. Wang B, Shao C, Li Y, Tan Y, Cai L (2012) Cadmium and its epigenetic effects. Curr Med Chem 19(16):2611–2620PubMedCrossRefPubMedCentralGoogle Scholar
  60. Wang L, Li H, Wei H, Wu X, Ke L (2013) Identification of cadmium-induced Agaricus blazei genes through suppression subtractive hybridization. Food Chem Toxicol 63:84–90PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of Biochemistry, Faculty of ScienceEkiti State University, Ado-EkitiAdo-EkitiNigeria
  2. 2.Department of Medical Biochemistry, College of MedicineEkiti State University, Ado-EkitiAdo- EkitiNigeria

Personalised recommendations