Influence of Phoenix dactylifera leaf extract on doxorubicin-induced nephrotoxicity and hepatotoxicity in rats

Abstract :

The research into plant is used to search for new agents with pharmacological activities. This study seeks to evaluate the effects of the palm leaf methanolic extract against nephrotoxicity, hepatotoxicity, and weight loss induced by chemotherapeutic drug doxorubicin in a rat’s model. Five groups of rats (n= 4 in each group) were treated with or without doxorubicin (3.0 mg/kg/day, ip) and with palm leaf methanolic extract (400 mg/kg/day or 1200 mg/kg/day, po), followed by evaluation of renal and hepatic biochemical markers. The findings obtained indicated that palm leaf methanolic extract exerts protective effects against doxorubicin-induced nephrotoxicity and hepatotoxicity. Doxorubicin significantly elevated renal function markers, namely creatinine, uric acid and urea, however, these biomarkers remained within normal levels after treatment with palm leaf methanolic extract (400 mg/kg/day) as compared to the control group. Treating the rats with doxorubicin and palm leaf methanolic extract at doses 400 mg/kg/day and 1200 mg/kg/day, counteracts the doxorubicin-induced elevation of serum creatinine and uric acid compared to the doxorubicin group. Doxorubicin also significantly increased hepatic function tests namely alanine and aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin as compared to the control group. In addition, treating the rats with palm leaf methanolic extract doses and doxorubicin caused a significant decrease in the serum levels of hepatic markers compared to the doxorubicin group. Doxorubicin treatment resulted in a weight loss of 34.1%, the weight loss caused by doxorubicin was prevented by treating the rats with the extract at 1200 mg/kg/day as compared to their baseline body weight. Thus, the results of the current study suggest that the active constituents present in the palm leaf methanolic extract have a protective effect against hepatotoxicity, nephrotoxicity and weight loss-induced by doxorubicin.

References

1. Prasad RB, Rathna VS, Nithish C Sowmya R, Arora A, Buchanalli S (2020) Cancer prevalence in south Indian hospitals: A prospective observational study. International Journal of Medical and Health Research. 6 (2): 48-51. doi. Nil.
2. Roy PS, Saikia BJ (2016) Cancer and cure: A critical analysis. Indian Journal of Cancer. 53 (3): 441-442. doi: 10.4103/0019-50 9X 200658
3. Rakoff-Nahoum S (2006) Cancer issue: why cancer and inflammation? The Yale Journal of Biology and Medicine. 79 (3-4): 123-130. PMID: 17940622. PMCID: PMC1994795.
4. Dejene TD, Seke M, Kidist D, Maureen N, Betelhiem WM, Dagimawi CH, Sophia K K, Tsegahun M (2021) New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Medicine. 9 (6): 1-10. doi: 101177/20503121211034366
5. Chaudhary, R, Karn B K (2012) Chemotherapy-knowledge and handling practice of nurses working in a medical university of Nepal. Journal of Cancer Therapy. 3 (1): 110-114. doi: 10.4236/j2012.31014
6. Huang CY, Ju DT, Chang CF, Reddy PM, Velmurugan BK (2017) A review on the effects of current chemotherapy drugs and natural agents in treating non-small cell lung cancer. Biomedicine. 7 (4): 23. doi: 10.151/bmdcn/2017070423
7. Wang Y, Chao, X, Shi, H, Mehbooh L, Hassan W (2019) Phoenix dactylifera protects against doxorubicin-induced cardiotoxicity and nephrotoxicity. Cardiology Research and Practice. 2019. 2019: 7395239. doi: 10.1155/2019/7. 395239
8. Jadhav A (2023) Doxorubicin: overview and toxicity. International Journal of Creative Research Thoughts. 11 (8): 780-790. doi: Nil.
9. Micallef I, Baron B (2020) Doxorubicin: an overview of the anti-cancer and chemoreistance mechanisms. Annals of Clinical Toxicology. 3 (2): 1031. doi: Nil.
10. Pureti LP, Kaviyarasi R, Abilash VG (2020) New molecular and biochemical insights of doxorubicin-induced hepatotoxicity. Life Sciences. 250 (1): 117599. doi: 10.1016/j.lfs.2020.117599
11. Abushouk AI, Salem AMA, Saad A (2019) Mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy: potential mechanisms, governing factors, and implications of the heart stem cell debate. Frontiers in Pharmacology. 10: 635. doi: 103389/fphar.00635
12. Lee VW, Harris DC (2011) Adriamycin nephropathy: a model of focal segmental glomerulosclerosis. Nephrology. 16 (1): 30-38. doi: 10.1111/J.1440-1797.2010.01383.x
13. Xiang C, Yan Y, Zhang D (2021) Alleviation of the doxorubicin-induced nephrotoxicity by fasudil in vivo and in vitro. Journal of Pharmacological Sciences. 145 (1): 6-15. doi: 10.1016/j.jphs.2020.10.002
14. Ali A, Naheed B, Muhammad T (2016) Phytochemical and therapeutic evaluation of date (Phoenix dactyligera). A Review. Journal of Pharmacy and Alternative Medicine. 9: 11-17. doi: Nil.
15. Laouini SE, Segni L, Ouahrani MR, Gherraf N, Mokni S (2012) Phytochemical analysis, antioxidant and antimicrobial activities of leaves extract of date palm grown in Algeria. Journal of Fundamental and Applied Sciences. 4 (2): 142-154. doi: 10.4314/jfas.v4i2.4
16. Abuelgassim AO (2010) Effect of flax seeds and date palm leaves extracts on serum concentrations of glucose and lipids in alloxan diabetic rats. Pakistan Journal of Biological Sciences. 13 (23): 1141-1145. doi: 10.3923/ pjbs.2010.1141.1145
17. Rania MM, Aisha SMF, Mohamed ME, Isam AMA (2014) Chemical composition, antioxidant capacity, and mineral extractability of Sudanese date palm (Phoenix dactylifera L.) fruits. Food Science and Nutrition. 2 (5): 478-489. doi: 10.1002/fsn 3.123
18. Bugoyne, RW, Tan DHS (2008) Prolongation and quality of life for HIV infected adults treated with highly active antiretroviral therapy (11AART) a balancing act. Journal of Antimicrobial Chemotherapy. 61 (3): 469-473. doi: 10.1093/jac/dkm499
19. Salem G, Shabana A, Diab H, Elsaghayer W, Mjedib M, Hnesh A, Sahue R (2018) Phoenix dactylifera protects against oxidative stress and hepatic injury induced by paracetamol intoxication in rats. Biomedicine and Pharmacotherapy. 104: 366-374. doi: 10.1016/j.biopha.2018.05.049
20. Pan YZ, Wang X, Bai L, Wang I, Zhang XR (2015) Autophagy in drug resistance of the multiple myeloma cell line RPM18226 to doxorubicin. Genetic and Molecular Research. 14 (2): 5621-5629. doi: 10.4238/2015. May.25.14
21. Ghibu S, Delemasure S, Richard C, Guilland J C, Martin L, Gambert S, Vergely C (2012) General oxidative stress during doxorubicin-induced cardiotoxicity in rats: absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid. Biochimic. 94 (4): 932-939. doi: 10.1016/j.biochi.02.015
22. Ayla S, Seckin I, Tanriverdi G, Cengiz M, Eser M, Soner B C, Oktem G (2011) Doxorubicin induced protective effect of nephrotoxicity: nicotinamide. International Journal of Cell Biology. 2011: 1-9. 390238. doi: 10.1155/ 2011 /390238
23. Diab H, El-Ahmer A, Kridis A, El-Gasri S, Sarfaraj H (2018) Evaluation of analgesic activities of Phoenix dactylifera L. leaflets extracts in mice. Advances in Biological Research. 12 (6): 191-198. doi: 10.5829/idosi. abr.2018.191.198
24. Diab H, Kridish A, El-Ahmer A, El-Gasri S, Abaurawi N, El- Karshin N, Abaurawi NO, Tiabin Z, Wqah S, Elginidi A (2018) A study of phytochemical screening and anticonvulsant activities of Phoenix dactylifera L. leaflets in animal models. Journal of Academia. 12 (6): 334-350. doi: Nil.
25. Saad AA, Youssef MI, El-Shennawy LK (2009) Cisplatin induced damage in kidney genomic DNA and nephrotoxicity in male rats: the protective effect of grape seed proanthocyanidin extract. Food and Chemical Toxicology. 47 (7): 1499-1506. doi: 10.1016/J.tct.2009.03.043
26. Ruggiero A, Ferrara P, Attina G, Rizzo D, Riccardi R (2017) Renal toxicity and chemotherapy in children with cancer. British Journal of Clinical Pharmacology. 83 (12): 2605-2614. doi: 10.1111/bcp.133388
27. Sachinthi SA, Anoja PA, lakmini KBM, Kamani AJ (2022) Doxorubicin-induced nephrotoxicity model in Wistar rats: Characterization of biochemical parameters, histological and immunohistochemical assessment. Ceylon Journal of Science. 51 (4): 471-479. doi: 10.4038/cjs.v51i4.8064
28. d'Alessandro LG, Kriaa K, Nikov I, Dimitrov K (2012) Ultrasound assisted extraction of polyphenols from black chokeberry. Separation and Purification Technology. 93: 42-47. doi: 10.1016/j.seppur.2012.03.024
29. Saleh D, Mahmoud S, Hassan A, Sanad E (2022) Doxorubicin-induced hepatic toxicity in rats: Mechanistc protective role of omega-3 fatty acids through Nrf2/HO-1 activation and PI3K/Akt/GSK-3 β axis modulation. Saudi Journal of Biological Sciences. 29 (7): 103308. doi: 10.1016j.sjbs.2022.103308
30. Wang B, Ma Y, Kong X, Ding X, Gu H, Chu T, Ying W (2014) NAD+ administration decreases doxorubicin-induced liver damage of mice by enhancing antioxidation capacity and decreasing DNA damage. Chemico-Biological Interactions. 212: 65-71. doi: 10.1016/j.cbi.2014.01.013
31. Chen X, Zhang Y, Zhu Z, Liu H, Guo H, Xiong C, Xie K, Zhang X, Su S (2016) Protective effect of berberine on doxorubicin-induced acute hepatorenal toxicity in rats. Molecular Medicine Reports. 13 (5): 3953-3960. doi: org/10.3892/mmr.2016.5017

Citation :

Diab et al. (2024) Influence of Phoenix dactylifera leaf extract on doxorubicin-induced nephrotoxicity and hepatotoxicity in rats. Mediterr J Pharm Pharm Sci. 4 (1): 75-83. [Article Number: 146]. https://doi.org/10.5281/zenodo.10711913