Can crocin play a preventive role in Wistar rats with carbon tetrachloride-induced nephrotoxicity?

Document Type : Original Article


1 Department of Medical Biochemistry, Medical Faculty, Nigde Omer Halisdemir University, Nigde, Turkey

2 Department of Histology and Embryology, Medical Faculty, Inonu University, Malatya, Turkey

3 Department of Medical Biochemistry, Medical Faculty, Karabuk University, Karabuk, Turkey

4 Department of Medical Biochemistry, Medical Faculty, Inonu University, Malatya, Turkey

5 Department of Biostatistics, Medical Faculty, Inonu University, Malatya, Turkey


Objective(s): To investigate protective role of crocin by attempting to create nephrotoxicity with carbon tetrachloride.
Materials and Methods: Ethics committee approval was obtained and 50 male Wistar rats were randomly divided into 5 groups that included 10 rats each: Control, Corn oil, Crocin, Carbon tetrachloride (CCl4), and Crocin + Carbon tetrachloride. Following the experiments, the rats were decapitated under anesthesia and incised kidney tissues were subjected to biochemical and histological examinations.
Results: In the CCl4 administered group, MDA, TOS, Bun, and creatinine levels increased, GSH, SOD, CAT, and TAS levels decreased (P≤0.05), glomerular collapse in kidney sections, narrowing and local occlusion in Bowman’s space in certain glomeruli, inflammatory cell infiltration and congestion were observed when compared to all other groups. There was a significant decrease in increased MDA, TOS, Bun, and creatinine levels, and a significant increase in decreased GSH, SOD, CAT, and TAS levels in CCl4 + crocin administered group compared to the CCl4 group (P≤0.05), local minimal glomerular damage, tubular damage, inflammatory infiltration, and vascular collagen symptoms were observed in kidney sections, however significant improvement was observed in damage findings when compared to the CCl4 group.
Conclusion: At this dose and time interval, against a highly toxic chemical such as CCl4, crocin was able to suppress oxidative stress by playing a protective role in the kidney tissue.


Main Subjects

1. Nasri H, Rafieian-Kopaei M. Protective effects of herbal antioxidants on diabetic kidney disease. J Res Med Sci 2014; 19: 82-83.
2. Nasri H, Rafieian-Kopaei M. Tubular kidney protection by antioxidants. Iran J Publ Health 2013; 42: 1194- 1196.
3. Olagunju JA, Adeneye AA, Fagbohunka BS, Bisuga NA, Ketiku AO. Nephroprotective activities of the aqueous seed extract of Carica papaya Linn. In carbon tetrachloride induced renal injured Wistar rats. Biol Med 2009; 1: 11-19.
4. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harpers Illustrated Biochemistry (Lange Medical Book) 29th ed. McGraw-Hill Medical 2014; 324-328.
5. Elshater AA, Salman MM, Mohamed SA. The hepato ameliorating effect of Salamun nigrum against CCL4 induced liver toxicity in albino rats. Egypt Acad J Biol Sci Physiol Mol Biol 2013; 5: 55-66.
6. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39: 44–84.
7. Dobreva ZG, Popov BN, Georgieva SY, Stanilova SA. Immunostimulatory activities of Haberlea rhodopensis leafextract on the specific antibody response: protective effects against c-radiation-induced immunosuppression. Food AgricImmunol 2015; 26: 381–393.
8. Chin Y-P, Hung C-Y, Yang C-Y, Wang C-Y, Lin Y-L. Immune modulation effects of soya bean fermentation food evaluated by an animal model. Food Agric Immunol 2015; 26: 463–476.
9. Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol 2003; 33: 105–136.
10. Knockaert L, Berson A, Ribault C, Prost PE, Fautrel A, Pajaud J, Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver. Lab Invest 2012; 92: 396–410.
11. Kader M, El-Sayed EM, Kassem SS, Mohamed HA, Eldin S. Protective and antioxidant effects of cynarascolymus leaves against carbon tetrachloride toxicity in rats. Res J Pharm Bio Chem Sci 2014;5: 1373-1380.
12. Amini FG, Rafieian-Kopaei M, Nematbakhsh M, Baradaran A, Nasri H. Ameliorative effects of metformin on renal histologic and biochemical alterations of gentamicin-induced renal toxicity in Wistar rats. J Res Med Sci. 2012; 17: 621-625.
13. Sewell RD, Rafieian-Kopaei M. The history and ups and downs of herbal medicine usage. J HerbMed Pharmacol 2014; 3: 1-3.
14. Bahmani M, Golshahi H, Saki K, Rafieian-Kopaei M, Delfan B, Mohammadi T. Medicinal plants and secondary metabolites for diabetes mellitus control. Asian Pac J Trop Dis. 2014;4 S687-S692.
15. Bahmani M, Shirzad HA, Majlesi M, Shahinfard N, Rafieian-Kopaei M. A review study on analgesic applications of Iranian medicinal plants. Asian Pac J Trop Med 2014; 7: 43-53.
16. Alavizadeh SH, Hosseinzadeh H. Bioactivity assessment and toxicity of crocin: A comprehensive review. Food Chem Toxicol 2014; 64: 65-80.
17. Amin B, Hosseinzadeh H. Evaluation of aqueous and ethanolic extracts of saffron, Crocus sativus L., and its constituents, safranal and crocin in allodynia and hyperalgesia induced by chronic constriction injury model of neuropathic pain in rats. Fitoterapia 2012;  83: 888-895.
18. Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. Extract and its bioactive constituents. Phytother Res 2005; 19: 997-1000.
19. Abdullaev FI, Espinosa‐Aguirre JJ. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Det Prev 2004; 28: 426-432.
20. Hosseinzadeh H, Karimi G, Niapoor M. Antidepressant effects of Crocus sativus stigma extracts and its constituents, crocin and safranal, in mice. J Med Plants 2004; 3: 48-58.
21. Vahdati Hassani F, Naseri V, Razavi B, Mehri S, Abnous K, Hosseinzadeh H. Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. DARU 2014; 22:16.
22. Moshiri M, Vahabzadeh M, Hosseinzadeh H. Clinical applications of saffron (Crocus sativus) and its constituents: a review. Drug Res 2015; 65: 287-95.
23. Rios, J.L., Recio, M.C., Giner, R.M., Manez, S.An update review of saffron and its active constituents. Phytother Res 1996;10, 189–193.
24. Hosseinzadeh H, Modaghegh MH, Saffari Z. Crocus sativus L.(Saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evid Complement Alternat Med 2009; 6: 343–350.
25. Uchiyama M, Mihara M.Determination of MDA precursor in tissue by TBA test. Anal Biochem1978;36: 271-278.
26. Elman G L.Tissue sulphydryl groups. Arch Biochem Biophys1979;95: 351–358.
27. Jolitha AB, Subramanyam MV, Devi SA.Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain: studies on superoxide dismutase isoenzymes and protein oxidation status. Exp Gerontol 2006; 41: 753–763.
28. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265–275.
29. Aebi H, Catalase BH. Methods of enzymatic analysis. Academic Press, New York and London 1974; 673–677.
30. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103-1111.
31. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37: 277-285.
32. Kus I, Ogeturk M, Oner H. Protective effects of melatonin against carbon  tetrachloride ‐induced hepatotoxicity in rats: a light microscopic and biochemical study. Cell  Biochem Funct 2005; 23: 169-174.
33. Brattin WJ, Glende EA, Recknagel RO. Pathological mechanisms in carbon  tetrachloride hepatotoxicity. J Free Radic Biol Med 1985; 1: 27-38.
34. Recknagel RO, Glende EA, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride  toxicity. Pharmacol Ther 1989; 43: 139-154.
35. Muriel P, Escobar Y. Kupffer cells are responsible for liver cirrhosis induced by 416 carbon tetrachloride. J Appl Toxicol 2003; 23: 103-108.
36. Hiroki Yoshioka, Miki Tanaka, Hirohisa Fujii, Tsunemasa Nonogaki. Sasa veitchii extract suppresses carbon tetrachloride-induced hepato- and nephrotoxicity in mice. Environ Health Prev Med 2016; 21: 554–562.
37. Karakuş A,Değer Y, Yıldırım S. Protective effect of Silybum marianum and Taraxacum officinale extracts against oxidative kidney injuries induced by carbon tetrachloride in rats. Ren Fail 2016; 39: 1-6.
38.Mirazi N, Movassagh SH, Kopaei MH. The protective effect of hydro-alcoholic extract of mangrove (Avicennia marina L.) leaves on kidney injury induced by carbon tetrachloride in male rats. J Nephropathol. 2016; 5: 118-22.
39. Yarijani ZM, Najafi H, Madani SM. Protective effect of crocin on gentamicin-induced nephrotoxicity in rats. Iran J Basic Med Sci. 2016; 19: 337–343.
40. Altinoz E, Ozmen T, Oner Z, Elbe H, Erdemli ME, Bag HG. Saffron (its active constituent, crocin) supplementation attenuates lipid peroxidation and protects against tissue injury. Bratisl Med J 2016; 117:381 – 387.
41. Adali F, Gonul Y, Aldemir M, et al Investigation of the effect of crocin pretreatment n renal injury induced by infrarenal aortic occlusion. JSR 2016; 203:145-153.
42. Samarghandian S, Azimi-Nezhad M, Farkhondeh ABT. Effect of crocin on aged rat kidney through inhibition of oxidative stress and proinflammatory state. Phytother. Res 2016; 30: 1345–1353.