LIVER TISSUE DAMAGE BY EFFECT OF TEMOZOLOMIDE DRUG
Keywords:
Liver, Histopathology, Temozolomide, Comet assay
Abstract
The new drug, Temozolomide, has been promising in the treatment of malignant gliomas and other tumours. Temozolomide is a new class of imidazotetrazine second-generation medications spontaneously converted into the active alkylating agent under physiological conditions. Use 30 of male albino rats for this purpose, divided into 3 groups, consisting of 10 rats in each group. A physiologic solution (normal saline 0.9 percent) was injected in Group 1 (controls), the drug was given to group 2 for 50 mg/kg/b.w/weekly and drug was received in group 3 for 12 weeks, with 80 mg/kg/b.w/weekly. The animals were killed at the end of the dose; the liver was excised for histologica. Histological exam of Temozolomide group liver tissues showed that histopathological changes increased with the increased dose of the treatments compared with the control group such as shows chronic hepatic edema around blood vessels with fibrosis, As well as there is chronic hepatic edema around blood vessels with fibrosis. Hepatocyte necrosis with ballooning degeneration in hepatocyte. Analysis of DNA damage through the use of the comet assessment kit. This result of comet assay showed that damage in DNA of liver cells at 12 weeks of treatment with Temozolomide different doses in four parameters comet high, comet medium, comet low, and no damage. With 50 mg/kg and 75 mg/kg of Temozolomide groups increase in comet high, comet medium percentage, decrease in comet low, and no damage percentage. The result of the present study indicated that 50 mg/kg/b.w. and 75 mg/kg/b.w. doses of Temozolomide able to induce Male albino rats' DNA liver damage.
References
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29. Zhang, J., M. F. Stevens, and T. D. Bradshaw. (2012). Temozolomide: mechanisms of action, repair and resistance. Curr. Mol. Pharmacol. 5:102–114.
2. Avgeropoulos, N. G., and Batchelor, T. T. (1999). New treatment strategies for malignant gliomas. Oncologist, 4: 209–224,
3. Bianchi, R., Citti, L., Beghetti, R., Romani, L., D’Incalci, M., Puccetti, P., and Fioretti, M. C. (1992). O6 -Methylguanine-DNA methyltransferase activity and induction of novel immunogenicity in murine tumor cells treated with methylating agents. Cancer Chemother. Pharmacol., 29: 277–282,
4. Bobola, M. S., M. Alnoor, J. Y. Chen, D. D. Kolstoe, D. L. Silbergeld, R. C. Rostomily, et al. (2015). O 6-methylguanine-DNA methyltransferase activity is associated with response to alkylating agent therapy and with MGMT promoter methylation in glioblastoma and anaplastic glioma. BBA Clin. 30:1.
5. Bull, V. L., and Tisdale, M. J. (1987). Antitumour imidazotetrazines-XVI macromolecular alkylation by 3-substituted imidazotetrazinones. Biochem. Pharmacol., 36: 3215–3220,
6. Colvin M. (2010). Alkylating agents and platinum antitumor compounds. In: Kufe DW, Frei E, Holland JF, et al, eds. Holland-Frei Cancer Medicine. 8th ed. Shelton, Connecticut: People’s Medical Publishing House.
7. De Boeck, M., Touil, N., De Visscher, G., Vande, P.A. and Kirsch– Volders, M. (2000). Validation and implementation of an internal standard in comet assay. Mutat.Res.469, 181-197.
8. Drummond, J. T., Li, G. M., Longley, M. J., and Modrich, P. (1995). Isolation of an hMSH2–p160 heterodimer that restores DNA mismatch repair to tumor cells. Science (Washington, DC), 268: 1909–1912,
9. Goldbecker A, Tryc AB, Raab P, et al. (2011); Hepatic encephalopathy after treatment with temozolomide. J Neurooncol. 103:163–166.
10. Goldbecker A, Tryc AB, Raab P, et al. (2011); Hepatic encephalopathy after treatment with temozolomide. J Neurooncol. 103:163–166.
11. Grewal J, Dellinger CA, Yung WK. (2007), Fatal reactivation of hepatitis B with temozolomide. N Engl J Med 356:1591-1592.
12. Hickman, J. A., Stevens, M. F. G., Gibson, N. W., Langdon, S. P., Fizames, C., Lavelle, F., Atassi, G., Lunt, E., and Tilson, R. M. (1985). Experimental antitumor activity against murine tumor model systems of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)- one (mitozolomide), a novel broad-spectrum agent. Cancer Res., 45: 3008–3013,
13. Karran, P., and Bignami, M. (1992). Self-destruction and tolerance in resistance of mammalian cells to alkylation damage. Nucleic Acids Res., 20: 2933–2940,
14. Karran, P., Macpherson, P., Ceccotti, S., Dogliotti, E., Griffin, S., and Bignami, M. (1993). O6 -methylguanine residues elicit DNA repair synthesis by human cell extracts. J. Biol. Chem., 268: 15878–15886,
15. Losa, M., F. Bogazzi, S. Cannavo, F. Ceccato, L. Curtò, L. De Marinis, et al. (2016). Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas. J. Neurooncol. 26:519–525.
16. Melchardt T, Magnes T, Weiss L, et al. (2014); Liver toxicity during temozolomide chemotherapy caused by Chinese herbs. BMC Complement Altern Med. 14:115.
17. Newlands ES, Stevens MF, Wedge SR, Wheelhouse RT, Brock C: (1997). Temozolomide: a review of its discovery, chemical properties, preclinical development and clinical trials. Cancer Treat Rev 23:35-61.
18. Patel, M., McCully, C., Godwin, K., and Balis, F. (1995). Plasma and cerebrospinal fluid pharmacokinetics of temozolomide. Proc. Am. Soc. Clin. Oncol., 14: 461,
19. Plowman, J., Waud, W. R., Koutsoukos, A. D., Rubinstein, L. V., Moore, T. D., and Grever, M. R. (1994). Preclinical antitumor activity of temozolomide in mice: efficacy against human brain tumor xenografts and synergism with 1,3-bis(2-chloroethyl)-1-nitrosourea. Cancer Res., 54: 3793–3799,
20. Puigvert, J. C., K. Sanjiv, and T. Helleday. (2016). Targeting DNA repair, DNA metabolism and replication stress as anti-cancer strategies. FEBS J. 283:232–245.
21. Rosner, B. (2010). Fundamentals of Biostatistics; Brooks/cole / cengage learning. Inc. Boston, USA.
22. Stevens, M. F. G., Hickman, J. A., Langdon, S. P., Chubb, D., Vickers, L., Stone, R., Baig, G., Goddard, C., Gibson, N. W., Slack, J. A., Newton, C., Lunt, E., Fizames, C., and Lavelle, F. (1987). Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4( 3H)-one (CCRG 81045: M & B39831), a novel drug with potential as an alternative to dacarbazine. Cancer Res., 47: 5846–5852,
23. Stevens, M. F. G., Hickman, J. A., Stone, R., Gibson, N. W., Baig, G. U., Lunt, E., and Newton, C. G. (1984). Antitumor imidazotetrazines. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d ]-1,2,3,5-tetrazin-4(3H)-one, a novel broad-spectrum antitumor agent. J. Med. Chem., 27: 196–201,
24. Suvarna, S.K., Layton, C. and Bancroft, J.D. (2013). Bancroft theory and practice of histological techniques.7th ed. Elsevier Lim, China.
25. Tajiri K, Shimizu Y. (2008). Practical guidelines for diagnosis and early management of drug-induced liver injury. World J Gastroenterol. 14:6774–6785.
26. Taverna, P., Catapano, C. V., Citti, L., Bonfanti, M., and D’Incalci, M. (1992). Influence of O6 -methylguanine on DNA damage and cytotoxicity of temozolomide in L1210 mouse leukemia sensitive and resistant to chloroethylnitrosoureas. Anticancer Drugs, 3: 401–405,
27. Tentori, L., Graziani, G., Gilberti, S., Lacal, P. M., Bonmassar, E., and D’Atri, S. (1995). Triazene compounds induce apoptosis in O6 -alkylguanine-DNA alkyltransferase deficient leukemia cell lines. Leukemia, 9: 1888–1895,
28. Wedge, S. R., Porteous, J. K., and Newlands, E. S. (1997). Effect of single and multiple administration of an O6 -benzylguanine/temozolomide combination: an evaluation in a human melanoma xenograft model. Cancer Chemother. Pharmacol., 40: 266–272,
29. Zhang, J., M. F. Stevens, and T. D. Bradshaw. (2012). Temozolomide: mechanisms of action, repair and resistance. Curr. Mol. Pharmacol. 5:102–114.
Published
2024-01-31
How to Cite
Hassan, S. S. A. (2024). LIVER TISSUE DAMAGE BY EFFECT OF TEMOZOLOMIDE DRUG. Central Asian Journal of Medical and Natural Science, 5(1), 511-523. Retrieved from https://cajmns.centralasianstudies.org/index.php/CAJMNS/article/view/2364
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