Protective effect of Crocus sativus stamens extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney

Samira  MAMRI; Nour Elhouda  DAOUDI; Mohamed  MARGHICH; Sabir  OUAHHOUD; Amine  KHOULATI; Mohammed  CHOUKRI; Abdeslam  ASEHRAOU; Mohamed  BNOUHAM; Ennouamane  SAALAOUI

doi:10.18006/2022.10(1).73.82

Authors

Samira MAMRI Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed First, Boulevard Mohamed VI; BP: 717; 60 000, Oujda, Morocco.
Nour Elhouda DAOUDI Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed First, Boulevard Mohamed VI; BP: 717; 60 000, Oujda, Morocco.
Mohamed MARGHICH Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed First, Boulevard Mohamed VI; BP: 717; 60 000, Oujda, Morocco.
Sabir OUAHHOUD Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed First, Boulevard Mohamed VI; BP: 717; 60 000, Oujda, Morocco.
Amine KHOULATI Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed First, Boulevard Mohamed VI; BP: 717; 60 000, Oujda, Morocco.
Mohammed CHOUKRI Biochemistry Laboratory, Central Laboratory Service - CHU, Mohammed VI, Oujda, Morocco.
Abdeslam ASEHRAOU Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed First, Boulevard Mohamed VI; BP: 717; 60 000, Oujda, Morocco.
Mohamed BNOUHAM Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed First, Boulevard Mohamed VI; BP: 717; 60 000, Oujda, Morocco.
Ennouamane SAALAOUI Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Department of Biology, Faculty of Sciences, University Mohamed First, Boulevard Mohamed VI; BP: 717; 60 000, Oujda, Morocco.

DOI:

https://doi.org/10.18006/2022.10(1).73.82

Keywords:

Stamens, Crocus sativus, Gentamicin, Oxidative stress, Nephroprotective

Abstract

Crocus sativus is a medicinal plant supposedly possessing various biological activities. Currently, it is evaluated only by the medicinal properties of its stigma and many parts of this plant are unused. This work contributes to the valorization of C.sativus stamens by exploring the property of methanolic extract to prevent gentamicin-induced nephrotoxicity in rats. Twenty Wistar rats (weight 250 ± 30g) were assigned into four equal groups (n = 5), and among the assigned groups, group 1 was given only distilled water (Control), group 2 received intraperitoneal (i.p.) injection of gentamicin (GEN) 80 mg/kg/d, group 3 received the combination of gentamicin (80 mg/kg/d, i.p.) and oral administration of a lower dose of C. sativus methanolic extract (250 mg/kg/d), while the group 4 received the combination of gentamicin (80 mg/kg/d, i.p.) and oral administration of a higher dose of C. sativus methanolic extract (500 mg/kg/d). The injection of gentamicin for the nephrotoxicity induction and post-treatment with methanolic extract was carried out once a day for 15 days. For nephrotoxicity evaluation, biochemical and histopathological analyses were performed. The estimation of serum and urinary creatinine, blood urea nitrogen, sodium levels was carried out with the help of Architect Ci 4100 Analyzer. Oxidative stress was assessed by the determination of renal malondialdehyde (MDA) and catalase (CAT) levels. The results of the study suggested that gentamicin injection induced a significant (p < 0.01) elevation in serum renal biochemical parameters and oxidative stress indices. The methanolic extract of C. sativus significantly (p < 0.05) reduced serum creatinine, urea, and sodium levels, with an improvement in the histopathological results of gentamicin-induced alterations. Furthermore, pretreatment with plant extracts improved hepatic antioxidant status, by the elevation of the CAT and reducing the lipid peroxidation level (MDA) in tissues. The present study suggests that the methanolic extract of C. sativus stamens has an interesting nephroprotective effect on the renal lesions induced by GEN in modulating renal parameters and oxidative stress on Wistar rats.

References

Aebi, H. (1984). Catalase in vitro. Methods in Enzymology, 105, 121–126. DOI: https://doi.org/10.1016/S0076-6879(84)05016-3

Akhondzadeh Basti, A., Moshiri, E., Noorbala, A.A., Jamshidi, A.H., Abbasi, S.H., & Akhondzadeh, S. (2007). Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31(2), 439–442. DOI: https://doi.org/10.1016/j.pnpbp.2006.11.010

Ali, B. H. (2003). Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: some recent research. Food and Chemical Toxicology, 41(11), 1447-1452. DOI: https://doi.org/10.1016/S0278-6915(03)00186-8

Balakumar, P., Chakkarwar, V. A., Kumar, V., Jain, A., Reddy, J., & Singh, M. (2008). Experimental models for nephropathy. Journal of the Renin-Angiotensin-Aldosterone System, 9(4), 189–195. DOI: https://doi.org/10.1177/1470320308098343

Bernardi, C., Monetal, D., Brughera, M., Di Salvo, M., Lamparelli, D., Mazué, G., & Iatropoulos, M. J. (1996). Haematology and clinical chemistry in rats: Comparison of different blood collection sites. Comparative Haematology International, 6(3), 160–166. 0 DOI: https://doi.org/10.1007/BF00368460

Choi, J. J., Moffett, B. S., McDade, E. J., & Palazzi, D. L. (2011). Altered gentamicin serum concentrations in obese pediatric patients. The Pediatric Infectious Disease Journal, 30(4), 347–349. DOI: https://doi.org/10.1097/INF.0b013e3181ff023e

Conly, J. M., Gold, W., & Shafran, S. D. (1994). Once-Daily Aminoglycoside Dosing: A New Look at an Old Drug. Canadian Journal of Infectious Diseases, 5, 796138. DOI: https://doi.org/10.1155/1994/796138

Draper, H. H., & Hadley, M. (1990). Malondialdehyde determination as index of lipid peroxidation. Methods in Enzymology, 186, 421–431. DOI: https://doi.org/10.1016/0076-6879(90)86135-I

Edeogu, C. O., Kalu, M. E., Famurewa, A. C., Asogwa, N. T., Onyeji, G. N., & Ikpemo, K. O. (2020). Nephroprotective Effect of Moringa Oleifera Seed Oil on Gentamicin-Induced Nephrotoxicity in Rats: Biochemical Evaluation of Antioxidant, Anti-inflammatory, and Antiapoptotic Pathways. Journal of the American College of Nutrition, 39(4), 307–315. DOI: https://doi.org/10.1080/07315724.2019.1649218

Ghaznavi, H., Fatemi, I., Kalantari, H., Hosseini Tabatabaei, S. M. T., et al. (2018). Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats. Journal of Asian Natural Products Research, 20(12), 1182—1193. DOI: https://doi.org/10.1080/10286020.2017.1384819

Ghaznavi, H., Mehrzadi, S., Dormanesh, B., Tabatabaei, S. M. T. H., et al. (2016). Comparison of the protective effects of melatonin and silymarin against gentamicin-induced nephrotoxicity in rats. Journal of Evidence-Based Complementary & Alternative Medicine, 21(4), NP49–NP55. DOI: https://doi.org/10.1177/2156587215621672

Ghuysen, M. S. (2005). Les médicaments dangereux pour le rein. Archives de Pédiatrie, 390(6), 643 YP – 1059. DOI: https://doi.org/10.1016/j.arcped.2005.04.059

Gilbert, D. N., Wood, C. A., Kohlhepp, S. J., Kohnen, P. W., et al. (1989). Polyaspartic acid prevents experimental aminoglycoside nephrotoxicity. Journal of Infectious Diseases, 159(5), 945–953. DOI: https://doi.org/10.1093/infdis/159.5.945

Hasanvand, A., Tavafi, M., Ahmadvand, H., & Tamjidipoor, A. (2019). Effect of dimethyl sulfoxide in combat with gentamicin induced nephrotoxicity in rats. Journal of Nephropathology, 9(3), e26. DOI: https://doi.org/10.34172/jnp.2020.26

Hosseinzadeh, H., & Younesi, H. M. (2002). Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacology, 2, 7.

Huang, J., Li, J., Lyu, Y., Miao, Q., & Pu, K. (2019). Molecular optical imaging probes for early diagnosis of drug-induced acute kidney injury. Nature Materials, 18(10), 1133–1143. DOI: https://doi.org/10.1038/s41563-019-0378-4

Janjua, A., Waheed, A., & Bakhtiar, S. (2014). Protective effect of metformin against gentamicin induced nephrotoxicity in rabbits. Pakistan Journal of Pharmaceutical Sciences, 27(6), 1863–1872.

Josiah, S. S., Crown, O. O., Akinmoladun, A. C., & Olaleye, M. T. (2020). Renoprotective property of the flavonoid-rich extract of Kigelia africana fruits on gentamicin-induced nephrotoxicity in rats. Comparative Clinical Pathology, 29(4), 815–828. DOI: https://doi.org/10.1007/s00580-020-03140-w

Kang, C., Lee, H., Hah, D. Y., Heo, J. H., et al. (2013). Protective effects of Houttuynia cordata Thunb. on gentamicin-induced oxidative stress and nephrotoxicity in rats. Toxicological Research, 29(1), 61–67. DOI: https://doi.org/10.5487/TR.2013.29.1.061

Karie, S., Launay-Vacher, V., Deray, G., & Isnard-Bagnis, C. (2010). Toxicité rénale des médicaments. Néphrologie & Thérapeutique, 6(1), 58–74. DOI: https://doi.org/10.1016/j.nephro.2009.02.006

Khan, M., Hanif, M. A., Ayub, M. A., Jilani, M. I., & Shahid Chatha, S. A. (2020). Saffron. In Hanif, M.A., Nawaz, H., Khan, M.M., Byrne, H.J. (eds), Medicinal Plants of South Asia (pp. 587–600), Elsevier Publication. DOI: https://doi.org/10.1016/B978-0-08-102659-5.00043-4

Khan, S. A., Priyamvada, S., Farooq, N., Khan, S., Khan, M. W., & Yusufi, A. N. K. (2009). Protective effect of green tea extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Pharmacological Research, 59(4), 254–262. DOI: https://doi.org/10.1016/j.phrs.2008.12.009

Khoulati, A., Ouahhoud, S., Mamri, S., Alaoui, K., et al. (2019). Saffron extract stimulates growth, improves the antioxidant components of Solanum lycopersicum L., and has an antifungal effect. Annals of Agricultural Sciences, 64(2), 138–150. DOI: https://doi.org/10.1016/j.aoas.2019.10.002

Lahmass, I., Ouahhoud, S., Elmansuri, M., Sabouni, A., et al. (2018). Determination of Antioxidant Properties of Six By-Products of Crocus sativus L. (Saffron) Plant Products. Waste and Biomass Valorization, 9(8), 1349–1357. DOI: https://doi.org/10.1007/s12649-017-9851-y

Montoro, P., Maldini, M., Luciani, L., Tuberoso, C. I. G., Congiu, F., & Pizza, C. (2012). Radical scavenging activity and LC-MS metabolic profiling of petals, stamens, and flowers of Crocus sativus L. Journal of Food Science, 77(8), C893-900. DOI: https://doi.org/10.1111/j.1750-3841.2012.02803.x

Morales-Alvarez, M. C. (2020). Nephrotoxicity of Antimicrobials and Antibiotics. Advances in Chronic Kidney Disease, 27(1), 31–37. DOI: https://doi.org/10.1053/j.ackd.2019.08.001

Moshiri, E., Basti, A. A., Noorbala, A.A., Jamshidi, A.H., Hesameddin Abbasi, S., & Akhondzadeh, S. (2006). Crocus sativus L. (petal) in the treatment of mild-to-moderate depression: a double-blind, randomized and placebo-controlled trial. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 13(9–10), 607–611. DOI: https://doi.org/10.1016/j.phymed.2006.08.006

Okokon, J. E., Nwafor, P. A., & Noah, K. (2011). Nephroprotective effect of Croton zambesicus root extract against gentimicin-induced kidney injury. Asian Pacific Journal of Tropical Medicine, 4(12), 969—972. DOI: https://doi.org/10.1016/S1995-7645(11)60228-9

Omidi, A., Riahinia, N., Montazer Torbati, M. B., & Behdani, M.A. (2014). Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats. Avicenna Journal of Phytomedicine, 4(5), 330–336. DOI: https://doi.org/10.4081/vsd.2015.5821

Ouahhoud, S., Touiss, I., Khoulati, A., Lahmass, I., et al. (2021). Hepatoprotective effects of hydroethanolic extracts of Crocus sativus tepals, stigmas and leaves on carbon tetrachloride induced acute liver injury in rats. Physiology & Pharmacology, 25(2), 10.32598/ppj.25.2.30. DOI: https://doi.org/10.32598/ppj.25.2.30

Ouahhoud, S., Lahmass, I., Bouhrim, M., Khoulati, A., et al. (2019). Antidiabetic effect of hydroethanolic extract of Crocus sativus stigmas, tepals and leaves in streptozotocin-induced diabetic rats. Physiology and Pharmacology, 23 (1) :9-20.

Ozbek, E. (2012). Induction of oxidative stress in kidney. International Journal of Nephrology, 2012, 465897. DOI: https://doi.org/10.1155/2012/465897

Raju, S., Kavimani, S., Uma Maheshwara rao, V., Sreeramulu Reddy, K., & Vasanth Kumar, G. (2011). Floral extract of Tecoma stans: A potent inhibitor of gentamicin-induced nephrotoxicity in vivo. Asian Pacific Journal of Tropical Medicine, 4(9), 680–685. DOI: https://doi.org/10.1016/S1995-7645(11)60173-9

Reiter, R. J., Tan, D.X., Sainz, R. M., Mayo, J. C., & Lopez-Burillo, S. (2002). Melatonin: reducing the toxicity and increasing the efficacy of drugs. The Journal of Pharmacy and Pharmacology, 54(10), 1299–1321. DOI: https://doi.org/10.1211/002235702760345374

Salama, A. A., Abd El-Wahed, A. S., & Mostafa, A. E. (2020). Protective effect of some plants against the toxicity of kidneys caused by gentamicin. Journal of Medicine in Scientific Research, 3(1), 5.

Sánchez-Vioque, R., Rodríguez-Conde, M. F., Reina-Ureña, J. V., Escolano-Tercero, M. A., Herraiz-Peñalver, D., & Santana-Méridas, O. (2012a). In vitro antioxidant and metal chelating

properties of corm, tepal and leaf from saffron (Crocus sativus L.). Industrial Crops and Products, 39(1), 149–153.

Sánchez-Vioque, R., Rodríguez-Conde, M. F., Reina-Ureña, J. V, Escolano-Tercero, M. A., Herraiz-Peñalver, D., & Santana-Méridas, O. (2012b). In vitro antioxidant and metal chelating properties of corm, tepal and leaf from saffron (Crocus sativus L.). Industrial Crops and Products, 39, 149–153. DOI: https://doi.org/10.1016/j.indcrop.2012.02.028

Vysakh, A., Abhilash, S., Kuriakose, J., Midhun, S. J., Jyothis, M., & Latha, M. S. (2018). Protective effect of Rotula aquatica Lour against gentamicin induced oxidative stress and nephrotoxicity in Wistar rats. Biomedicine & Pharmacotherapy, 106, 1188–1194. DOI: https://doi.org/10.1016/j.biopha.2018.07.066

Wali, A. F., Alchamat, H. A. A., Hariri, H. K., Hariri, B. K., et al. (2020). Antioxidant, Antimicrobial, Antidiabetic and Cytotoxic Activity of Crocus sativus L. Petals. Applied Sciences, 10(4), 1519. DOI: https://doi.org/10.3390/app10041519