The Protective Effects of Saffron Stigma Alcoholic Extract against Vincristine Sulfate Drug-Induced Renal Toxicity in Rat Saffron extract mitigate vincristine-induced renal toxicity
Iranian Journal of Pharmaceutical Sciences,
Vol. 15 No. 4 (2019),
1 October 2019
,
Page 83-94
https://doi.org/10.22037/ijps.v15.40466
Abstract
Vincristine (VCR) is a potential anti-cancer drug which is highly toxic for renal tissue. This study aims to evaluate the protective effect of alcoholic extract of saffron stigma against vincristine renal toxicity in male rats. A total of 50 rats were randomly divided into 10 groups. Different doses of VCR (0.25, 0.5 and 0.75mg/kg) and saffron (0.5 and 1mg/kg) were used to treat vincristine-induced renal toxicity in rats. Serum levels of creatinine (Cr), uric acid and blood urea nitrogen (BUN) were measured using specific kits at the end of the experimental period. Serum total antioxidant capacity (TAC) and malondialdehyde (MDA) values were measured using Ferric reducing antioxidant of power (FRAP) and Thiobarbituric acid reaction (TBAR) methods, respectively. Administration of VCR caused severe renal injury with significant increase in the levels of Cr, uric acid and BUN. VCR administration (at concentration of 0.75mg/kg) significantly increased the mean level of MDA (0.51±0.021 nmol/ml; p<0.001), while TAC value was declined significantly (243.17±16.24 μmol/l; p<0.001). These effects were dose-dependently. Treatment with saffron extract decreased the level of Cr, BUN, and MDA values in VCR-exposed rats with a significant enhancement in serum TAC content. This effect was notable for rats that received 1mg/kg plant extract. Administration of saffron, especially at higher concentration, can reduce VCR-induced renal toxicity, depletion of total antioxidant and lipid peroxidation, possibly due to its antioxidative properties.
Keywords:
- Vincristine
- saffron extract
- renal toxicity
- TAC
- MDA
- oxidative stress
How to Cite
Beigi Harchegani, A. ., Sohrabiyan, M. ., Bakhtiari Kaboutaraki, H. ., Shirvani, H. ., & Shahriary, A. . (2019). The Protective Effects of Saffron Stigma Alcoholic Extract against Vincristine Sulfate Drug-Induced Renal Toxicity in Rat: Saffron extract mitigate vincristine-induced renal toxicity. Iranian Journal of Pharmaceutical Sciences, 15(4), 83–94. https://doi.org/10.22037/ijps.v15.40466
References
[1] Kumar A, et al. Isolation, purification and characterization of vinblastine and vincristine from endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus. PLoS One. (2013) 8 (9) p.e71805.
[2] Silverman JA and Deitcher SR, Marqibo(R) (vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother Pharmacol. (2013) 71(3) 555-64.
[3] Gidding CE, et al. Vincristine revisited. Crit. Rev.Oncol. Hematol. (1999) 29(3): 267-87.
[4] van Tellingen O, et al. Pharmacology, bio-analysis and pharmacokinetics of the vinca alkaloids and semisynthetic derivatives (review). Anticancer. Res.(1992) 12 (5): 1699-715.
[5] Blajeski AL, et al. G(1) and G(2) cell-cycle arrest following microtubule depolymerization in human breast cancer cells. J. Clin. Invest. (2002) 110(1): 91-9.
[6] Jordan MA, Thrower D, Wilson L. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J. Cell Sci. (1992).102 ( Pt 3): 401-16.
[7] Geyp M, Ireland CM, Pittman SM. Resistance to apoptotic cell death in a drug resistant T cell leukaemia cell line. Leukemia. (1996) 10(3): 447-55.
[8] Takano Y, Okudaira M, Harmon BV. Apoptosis induced by microtubule disrupting drugs in cultured human lymphoma cells. Inhibitory effects of phorbol ester and zinc sulphate. Pathol Res Pract. (1993) 189
(2): 197-203.
[9] Thakur V, et al. Vincristine sulfate loaded dextran microspheres amalgamated with thermosensitive gel offered sustained release and enhanced cytotoxicity in THP-1, human leukemia cells: In vitro and in vivo
study. Mater. Sci. Eng. C. Mater. Biol. Appl. (2016).61: 113-22.
[10] el Saghir NS, Hawkins KA. Hepatotoxicity following vincristine therapy. Cancer (1984) 54(9):2006-8.
[11] Schrek R, Stefani SS. Inhibition by ionophore A23187 of the cytotoxicity of vincristine, colchicine and X-rays to leukemic lymphocytes. Oncology (1976) 33(3): 132-5.
[12] Nevalainen TJ. Cytotoxicity of vinblastine and vincristine to pancreatic acinar cells. Virchows Arch B. Cell Pathol. (1975) 18(2): 119-27.
[13] Ogunc Y, et al. Vincristine and varepsilonviniferine-loaded PLGA-b-PEG nanoparticles:pharmaceutical characteristics, cellular uptake and cytotoxicity. J. Microencapsul (2017) 34 (1): 38-46.
[14] Mashmoul M, et al. Saffron: A Natural Potent Antioxidant as a Promising Anti-Obesity Drug.Antioxidants (Basel). (2013) 2 (4): 293-308.
[15] Verma SK, Bordia A. Antioxidant property of Saffron in man. Indian J. Med Sci. (1998) 52 (5):205-7.
[16] Nair SC, Kurumboor SK, Hasegawa JH. Saffron chemoprevention in biology and medicine: a review.Cancer Biother. (1995) 10(4): 257-64.
[17] Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats. Indian Heart J. (2017) 69 (2): 151-159.
[18] Kamalipour M, Akhondzadeh S. Cardiovascular effects of saffron: an evidence-based review. J.Tehran Heart Cent. (2011) 6(2): 59-61.
[19] Assimopoulou AN, Sinakos Z, Papageorgiou VP.Radical scavenging activity of Crocus sativus L.extract and its bioactive constituents. Phytother Res.(2005) 19 (11): 997-1000.
[20] He SY, et al. Effect of crocin on experimental atherosclerosis in quails and its mechanisms. Life Sci.(2005) 77 (8): 907-21.
[21] Benzie IF, Strain J. The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power":the FRAP assay. Anal Biochem. (1996) 239(1): 70-6.
[22] Tavilani H, Doosti M, Saeidi H.Malondialdehyde levels in sperm and seminal plasma of asthenozoospermic and its relationship with semen parameters. Clin. Chim. Acta. (2005) 356(1-2): 199-203.
[23] Hosseinzadeh H, et al. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemiareperfusion-induced oxidative damage in rats. J.Pharm. Pharm. Sci. (2005) 8(3): 387-93.
[24] Mahmoudzadeh L, et al. Anti-inflammatory and protective effects of saffron extract in ischaemia/reperfusion-induced acute kidney injury.Nephrology (Carlton) (2017) 22 (10): 748-754.
[25] Chahine N, et al. Cardioprotective effect of saffron extracts against acute doxorubicin toxicity in isolated rabbit hearts submitted to ischemiareperfusion injury. Z. Naturforsch C. (2014) 69 (11-12): 459-70.
[26] El-Beshbishy HA, et al. Crocin "saffron" protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antioxidant enzymes. Ecotoxicol
Environ. Saf. (2012) 83: 47-54.
[27] Shati AA, Alamri SA. Role of saffron (Crocus sativus L.) and honey syrup on aluminum-induced hepatotoxicity. Saudi Med. J. (2010) 31 (10): 1106-13.
[28] Omidi A, et al. Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats. Avicenna J Phytomed.(2014) 4 (5): 330-6.
[29] Mashmoul M, et al. Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats. BMC.Complement. Altern. Med. (2016) 16 (1): 401.
[30] Harrington M. Saffron offers protection from liver cancer. Lab Anim. (NY). (2011) 40 (10): 289.
[31] Amin A, et al. Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses. Recent Pat. Anticancer Drug Discov. (2016) 11 (1): 121-33.
[32] Hosseini A, et al. Effect of saffron on liver metastases in patients suffering from cancers with liver metastases: A randomized, double blind,placebo-controlled clinical trial. Avicenna J.Phytomed. (2015) 5(5): 434-40.
[33] Martins DB, et al. Lipid peroxidation in rats treated with vincristine sulphate and nandrolone decanoate. Arq. Bras. Med. Vet. Zootec. (2011) 63:107-113.
[34] Pan TL, et al. Functional proteomics reveals the protective effects of saffron ethanolic extract on hepatic ischemia-reperfusion injury. Proteomics.(2013) 13 (15): 2297-311.
[35] Ghaffari S, Hatami H, Dehghan G. Saffron ethanolic extract attenuates oxidative stress, spatial learning, and memory impairments induced by local injection of ethidium bromide. Res. Pharm. Sci.(2015) 10 (3): 222-32.
[36] Samarghandian S, Azimi-Nezhad M. Samini F.Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced
experimental diabetes mellitus. Biomed. Res. Int.(2014) 2014: 920857.
[37] Das I, Das S, Saha T. Saffron suppresses oxidative stress in DMBA-induced skin carcinoma: A histopathological study. Acta Histochem. (2010) 112 (4): 317-27.
[38] Koul A, Abraham SK. Intake of saffron reduces gamma-radiation-induced genotoxicity and oxidative stress in mice. Toxicol. Mech. Methods (2017) 27 (6):428-434.
[39] Ben Salem I, et al. Crocin, the main active saffron constituent, mitigates dichlorvos-induced oxidative stress and apoptosis in HCT-116 cells.Biomed. Pharmacother. (2016) 82: 65-71.
[40] Premkumar K, et al. Protective effects of saffron (Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice. Phytother. Res.(2003) 17 (6): 614-7.
[2] Silverman JA and Deitcher SR, Marqibo(R) (vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother Pharmacol. (2013) 71(3) 555-64.
[3] Gidding CE, et al. Vincristine revisited. Crit. Rev.Oncol. Hematol. (1999) 29(3): 267-87.
[4] van Tellingen O, et al. Pharmacology, bio-analysis and pharmacokinetics of the vinca alkaloids and semisynthetic derivatives (review). Anticancer. Res.(1992) 12 (5): 1699-715.
[5] Blajeski AL, et al. G(1) and G(2) cell-cycle arrest following microtubule depolymerization in human breast cancer cells. J. Clin. Invest. (2002) 110(1): 91-9.
[6] Jordan MA, Thrower D, Wilson L. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J. Cell Sci. (1992).102 ( Pt 3): 401-16.
[7] Geyp M, Ireland CM, Pittman SM. Resistance to apoptotic cell death in a drug resistant T cell leukaemia cell line. Leukemia. (1996) 10(3): 447-55.
[8] Takano Y, Okudaira M, Harmon BV. Apoptosis induced by microtubule disrupting drugs in cultured human lymphoma cells. Inhibitory effects of phorbol ester and zinc sulphate. Pathol Res Pract. (1993) 189
(2): 197-203.
[9] Thakur V, et al. Vincristine sulfate loaded dextran microspheres amalgamated with thermosensitive gel offered sustained release and enhanced cytotoxicity in THP-1, human leukemia cells: In vitro and in vivo
study. Mater. Sci. Eng. C. Mater. Biol. Appl. (2016).61: 113-22.
[10] el Saghir NS, Hawkins KA. Hepatotoxicity following vincristine therapy. Cancer (1984) 54(9):2006-8.
[11] Schrek R, Stefani SS. Inhibition by ionophore A23187 of the cytotoxicity of vincristine, colchicine and X-rays to leukemic lymphocytes. Oncology (1976) 33(3): 132-5.
[12] Nevalainen TJ. Cytotoxicity of vinblastine and vincristine to pancreatic acinar cells. Virchows Arch B. Cell Pathol. (1975) 18(2): 119-27.
[13] Ogunc Y, et al. Vincristine and varepsilonviniferine-loaded PLGA-b-PEG nanoparticles:pharmaceutical characteristics, cellular uptake and cytotoxicity. J. Microencapsul (2017) 34 (1): 38-46.
[14] Mashmoul M, et al. Saffron: A Natural Potent Antioxidant as a Promising Anti-Obesity Drug.Antioxidants (Basel). (2013) 2 (4): 293-308.
[15] Verma SK, Bordia A. Antioxidant property of Saffron in man. Indian J. Med Sci. (1998) 52 (5):205-7.
[16] Nair SC, Kurumboor SK, Hasegawa JH. Saffron chemoprevention in biology and medicine: a review.Cancer Biother. (1995) 10(4): 257-64.
[17] Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats. Indian Heart J. (2017) 69 (2): 151-159.
[18] Kamalipour M, Akhondzadeh S. Cardiovascular effects of saffron: an evidence-based review. J.Tehran Heart Cent. (2011) 6(2): 59-61.
[19] Assimopoulou AN, Sinakos Z, Papageorgiou VP.Radical scavenging activity of Crocus sativus L.extract and its bioactive constituents. Phytother Res.(2005) 19 (11): 997-1000.
[20] He SY, et al. Effect of crocin on experimental atherosclerosis in quails and its mechanisms. Life Sci.(2005) 77 (8): 907-21.
[21] Benzie IF, Strain J. The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power":the FRAP assay. Anal Biochem. (1996) 239(1): 70-6.
[22] Tavilani H, Doosti M, Saeidi H.Malondialdehyde levels in sperm and seminal plasma of asthenozoospermic and its relationship with semen parameters. Clin. Chim. Acta. (2005) 356(1-2): 199-203.
[23] Hosseinzadeh H, et al. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemiareperfusion-induced oxidative damage in rats. J.Pharm. Pharm. Sci. (2005) 8(3): 387-93.
[24] Mahmoudzadeh L, et al. Anti-inflammatory and protective effects of saffron extract in ischaemia/reperfusion-induced acute kidney injury.Nephrology (Carlton) (2017) 22 (10): 748-754.
[25] Chahine N, et al. Cardioprotective effect of saffron extracts against acute doxorubicin toxicity in isolated rabbit hearts submitted to ischemiareperfusion injury. Z. Naturforsch C. (2014) 69 (11-12): 459-70.
[26] El-Beshbishy HA, et al. Crocin "saffron" protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antioxidant enzymes. Ecotoxicol
Environ. Saf. (2012) 83: 47-54.
[27] Shati AA, Alamri SA. Role of saffron (Crocus sativus L.) and honey syrup on aluminum-induced hepatotoxicity. Saudi Med. J. (2010) 31 (10): 1106-13.
[28] Omidi A, et al. Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats. Avicenna J Phytomed.(2014) 4 (5): 330-6.
[29] Mashmoul M, et al. Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats. BMC.Complement. Altern. Med. (2016) 16 (1): 401.
[30] Harrington M. Saffron offers protection from liver cancer. Lab Anim. (NY). (2011) 40 (10): 289.
[31] Amin A, et al. Saffron-Based Crocin Prevents Early Lesions of Liver Cancer: In vivo, In vitro and Network Analyses. Recent Pat. Anticancer Drug Discov. (2016) 11 (1): 121-33.
[32] Hosseini A, et al. Effect of saffron on liver metastases in patients suffering from cancers with liver metastases: A randomized, double blind,placebo-controlled clinical trial. Avicenna J.Phytomed. (2015) 5(5): 434-40.
[33] Martins DB, et al. Lipid peroxidation in rats treated with vincristine sulphate and nandrolone decanoate. Arq. Bras. Med. Vet. Zootec. (2011) 63:107-113.
[34] Pan TL, et al. Functional proteomics reveals the protective effects of saffron ethanolic extract on hepatic ischemia-reperfusion injury. Proteomics.(2013) 13 (15): 2297-311.
[35] Ghaffari S, Hatami H, Dehghan G. Saffron ethanolic extract attenuates oxidative stress, spatial learning, and memory impairments induced by local injection of ethidium bromide. Res. Pharm. Sci.(2015) 10 (3): 222-32.
[36] Samarghandian S, Azimi-Nezhad M. Samini F.Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced
experimental diabetes mellitus. Biomed. Res. Int.(2014) 2014: 920857.
[37] Das I, Das S, Saha T. Saffron suppresses oxidative stress in DMBA-induced skin carcinoma: A histopathological study. Acta Histochem. (2010) 112 (4): 317-27.
[38] Koul A, Abraham SK. Intake of saffron reduces gamma-radiation-induced genotoxicity and oxidative stress in mice. Toxicol. Mech. Methods (2017) 27 (6):428-434.
[39] Ben Salem I, et al. Crocin, the main active saffron constituent, mitigates dichlorvos-induced oxidative stress and apoptosis in HCT-116 cells.Biomed. Pharmacother. (2016) 82: 65-71.
[40] Premkumar K, et al. Protective effects of saffron (Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice. Phytother. Res.(2003) 17 (6): 614-7.
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