Administration of Thymoquinone Offer a Protective Effect through the Apoptogenic and Antioxidant Pathway in Acute Liver Failure induced by Taxol
Thymoquinone and Taxol effects on liver
AbstractObjectives Due to the increasing use of chemotherapy drug and herbs in medicine, this study was designed to assess the effects of Thymoquinone and Taxol on apoptogenic, oxidative and histomorphometric changes in liver.
Methods Sixty-four male rats were assigned to 8 groups including control groups (normal group and Taxol (20 mg/kg group), Thymoquinone groups (4.5, 9, 18 mg/kg) and Taxol + Thymoquinone (TT) treated groups. All experimental groups were treated intraperitoneally daily for two weeks. The relative expression level of apoptotic genes and hepatocyte apoptotic index were analyses. Also, Nitrite oxide (NO), lipid peroxidation (LP), total antioxidant capacity (TAC), hepatic enzymes and histomorphometric parameters were evaluated.
Results In the Taxol control group (TCG) all parameters investigated in this study significantly increase except TAC level, which was decreased in compared to the normal control group (NCG) (P < 0.01). Additionally, all evaluated parameters were reduced in Thymoquinone and TT groups, except TAC level (which was increased) as compared to the TCG (P < 0.01).
Conclusion Our results discovered that Thymoquinone successfully moderate liver injury induced by Taxol through the activation of antioxidant pathways, reduce the apoptogenic and the regeneration of histopathological alterations.
2. Nazhand A, Durazzo A, Lucarini M, Mobilia MA, Omri B, Santini A. Rewiring cellular metabolism for heterologous biosynthesis of Taxol. Nat Prod Res. 2020;34(1):110-21.
3. Salahshoor MR, Roshankhah S, Hosseni P, Jalili C. Genistein Improves Liver Damage in Male Mice Exposed to Morphine. Chin Med J 2018;131:1598-604.
4. Firozi-Niyaki M, Barari AR, Abbassi-Daloii A. The effect of endurance training and taxol consumption on cyclooxygenase-2 and prostaglandin E2 levels in the liver tissue of mice with cervical cancer. J kashan univ med sci. 2018;22:517-24.
5. Karaduman D, Eren B, Keles ON. The protective effect of beta-1, 3-D-glucan on taxol-induced hepatotoxicity: a histopathological and stereological study. Drug Chem Toxicol. 2010;33:8-16.
6. Salahshoor MR, Vahabi A, Roshankhah Sh, Shabanizadeh Darehdori A, Jalili C. The effects of Thymoquinone against morphine-induced damages on male mice liver. Int J Prev Med. 2018;9:8
7. Salahshoor MR, Abdolmaleki A, Jalili C, Roshankhah S, Ziapour A. Determination of histopathological and biomedical parameters in protective effects of Petroselinum crispum on hepatotoxicity induced by dichlorvos in male Wistar rats. Comp Clin Path. 2020;2:1-9.
8. Ali BM, Velavan B, Sudhandiran G, Sridevi J, Nasar AS. Radical dendrimers: Synthesis, anti-tumor activity and enhanced cytoprotective performance of TEMPO free radical functionalized polyurethane dendrimers. Eur Polym J. 2020;122:109354.
9. Jayakumar T, Huang HC, Hsia CW, Fong TH, Khamrang T, Velusamy M, et al. Ruthenium derivatives attenuate LPS-induced inflammatory responses and liver injury via suppressing NF-κB signaling and free radical production. Bioorg Chem. 2020;96:103639.
10. Karaduman D, Eren B, Keles ON. The protective effect of beta-1, 3-D-glucan on taxol-induced hepatotoxicity: a histopathological and stereological study. Drug Chem Toxicol. 2010;33:8-16.
11. Mazaheri Y, Torbati M, Azadmard-Damirchi S, Savage GP. Effect of roasting and microwave pre-treatments of Nigella sativa L. seeds on lipase activity and the quality of the oil. Food Chem. 2019;274:480-6.
12. Mukhtar H, Qureshi AS, Anwar F, Mumtaz MW, Marcu M. Nigella sativa L. seed and seed oil: potential sources of high-value components for development of functional foods and nutraceuticals/pharmaceuticals. Essent oil res. 2019;14:1-3.
13. Kausar H, Mujeeb M, Ahad A, Moolakkadath T, Aqil M, Ahmad A, et al. Optimization of ethosomes for topical Thymoquinone delivery for the treatment of skin acne. J Drug Deliv Sci Technol. 2019;49:177-87.
14. Geng D, Zhang S, Lan J. Analysis on chemical components of volatile oil and determination of Thymoquinone from seed of Nigella glandulifera. Zhongguo Zhong Yao Za Zhi. 2009;34:2887-90.
15. Daba MH. Hepatoprotective activity of Thymoquinone in isolated rat hepatocytes. Toxicol Lett. 1998;95:23-9.
16. Esfandiari E, Roshankhah S, Mardani M, Hashemibeni B, Naghsh E, Kazemi M, et al. The effect of high frequency electric field on enhancement of chondrogenesis in human adipose-derived stem cells. Iran J Basic Med Sci. 2014;17:571-76.
17. Bridgewater JA, Pugh SA, Maishman T, Eminton Z, Mellor J, Whitehead A, et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2020;21:398-411.
18. Zhang Y, Wu Z, Yu H, Wang H, Liu G, Wang S, et al. Chinese Herbal Medicine Wenxia Changfu Formula Reverses Cell Adhesion-Mediated Drug Resistance via the Integrin β1-PI3K-AKT Pathway in Lung Cancer. J Cancer. 2019;10:293-304.
19. Dera A, Rajagopalan P. Thymoquinone attenuates phosphorylation of AKT to inhibit kidney cancer cell proliferation. J Food Biochem. 2019;e12793.
20. Gani M. Evalution of hepatoprotective effect of nigaella satival. J Pharm Pharm Sci. 2013;4:428-30.
21. Meshkini A, Yazdanparast R. Involvement of oxidative stress in taxol-induced apoptosis in chronic myelogenous leukemia K562 cells. Exp Toxicol Pathol. 2012;64:357-65.
22. Raushan HR, Seth PK. Bihavioral neurochemical and neuromorphological effects of deltamethrin in adult rats. J Toxicol Environ Health. 2010;48:515- 6.
23. Amouoghli Tabrizi B MD. Protective effect of edible turmeric powder on early hepatic injury in diabetic rats. J kashan univ med sci. 2010;14:190-9.
24. Cresteil T, Monsarrat B, Alvinerie P, Tréluyer JM, Vieira I, Wright M. Taxol metabolism by human liver microsomes: identification of cytochrome P450 isozymes involved in its biotransformation. Cancer Res. 1994;54:386-92.
25. Bai T, Lian LH, Wu YL, Wan Y, Nan JX. Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells. Int J Immunopharmacol. 2013;15:275-81.
26. Nagi MN, Almakki HA, Sayed-Ahmed MM, Al-Bekairi AM. Thymoquinone supplementation reverses acetaminophen-induced oxidative stress, nitric oxide production and energy decline in mice liver. Food Chem Toxicol. 2010;48:2361-5.
27. Kumar GN, Walle UK, Walle T. Cytochrome P450 3A-mediated human liver microsomal taxol 6 alpha-hydroxylation. J Pharmacol Exp Ther. 1994;268:1160-5.
28. Nili-Ahmadabadi A, Tavakoli F, Hasanzadeh GR, Rahimi HR, Sabzevari O. Protective effect of pretreatment with Thymoquinone against Aflatoxin B1 induced liver toxicity in mice. Daru. 2011;19:282.
29. Harris JW, Rahman A, Kim BR, Guengerich FP, Collins JM. Metabolism of taxol by human hepatic microsomes and liver slices: participation of cytochrome P450 3A4 and an unknown P450 enzyme. Cancer Res. 1994;54:4026-35.
30. Harris JW, Rahman A, Kim BR, Guengerich FP, Collins JM. Metabolism of taxol by human hepatic microsomes and liver slices: participation of cytochrome P450 3A4 and an unknown P450 enzyme. Cancer Res. 1994;54:4026-35.
31. Pari L, Sankaranarayanan C. Beneficial effects of Thymoquinone on hepatic key enzymes in streptozotocin–nicotinamide induced diabetic rats. Life Sci. 2009;85:830-4.
32. Al Humayed S, Al-Hashem F, Haidara MA, El Karib AO, Kamar SS, Amin SN, et al. Resveratrol pretreatment ameliorates p53-Bax axis and augments the survival biomarker B-cell lymphoma 2 modulated by paracetamol overdose in a rat model of acute liver injury. Pharmacol. 2020;105:39-46.
33. Minero VG, De Stefanis D, Costelli P, Baccino FM. and in vivo conditional sensitization of hepatocellular carcinoma cells to TNF-induced apoptosis by Taxol. Cell cycle.2020;14:1090-1102.
34. Chae IG, Song NY, Kim DH, Lee MY, Park JM, Chun KS. Thymoquinone induces apoptosis of human renal carcinoma Caki-1 cells by inhibiting JAK2/STAT3 through pro-oxidant effect. Food Chem Toxicol. 2020;9:253-259.
35. De A, De A, Sharma R, Suo W, Sharma M. Sensitization of Carboplatinum-and Taxol-Resistant High-Grade Serous Ovarian Cancer Cells Carrying p53, BRCA1/2 Mutations by Emblica officinalis (Amla) via Multiple Targets. J Cancer. 2020;11:1927-39.