Reducing the side effects of cancer chemotherapy is an important task for clinicians and researchers. The role of free radical processes in carcinogenesis is established and  studies of free radical scavengers are intensive. In our study on the  activity of KP972 (derivative of pyridopyrazolopyrimidine i.e. 4-phenyl-2-(4'-trifluoromethyl-beta-styryl)pyrido (2',3':3,4)pyrazolo(1,5-a)pyrimidine in comparison with  cisplatin, we found that cisplatin toxicity is associated significantly with the generation of free radicals [1,2]. This is  also confirmed by the clinical observations (an increase of MDA-malondialdehyde in the urine of patients) [3]. There is information about beneficial effects of antioxidants (vitamins C and E, N-acetylcysteine​​) in the treatment of cisplatin [4] Our in vitro study demonstrated that oxidative stress caused by xenobiotics can be in some of cases effectively inhibited by coenzyme Q10 (CoQ10) [5].

Currently presented research concerns the assessment of the effectiveness of a new soluble in water form of coenzymeQ10- P40 (PureSorb-Q ^TM40) in relation to cisplatin. The study was performed on an in vitro model of human erythrocyte. The degree of lipid peroxidation in the erythrocytes was measured as the TBARS (thiobarbituric active reagent species)level according to Stocke’s method. The hydroxyl radical (OH·) concentration was determined by deoxyribose degradation, while the activity of antioxidant enzymes : SOD (superoxide dismutase) and GPx (glutathione peroxidase), using Randox kits. Final verification of the suitability of a new form P40 as an antioxidant has been leading as a series of the same experience with fat-soluble CoQ10.

  In our observations new form - P40 and lipophilic CoQ10 decreased TBARS level in red blood cell. Furthermore, it was observed that both forms of antioxidant acted protectively in concentrations: 1,0 - 120 μg/ml in oxidative stress induced by cisplatin. Inhibition of lipid peroxidation, elevated after  exposure to cisplatin, was  more effective in the higher doses   (20 -120 μg/ml) of P40 or CoQ10. The influence of P40 on antioxidant enzymes activity was  varied, causing both an increase and decrease of their activity. During our in vitro studies we didn’t obtained  significant differences between the effects of the two forms of CoQ10 on lipid peroxidation. It can be assumed that the solubility in water of P40 is important rather at the stage of absorption in vivo  but not during action in cells.

References:

1.        1. Sawicka E., Długosz A., Poręba K., Chowaniec A.: Difssimilar effects of cisplatin and the pyridopyrazolopyrimidine derivative of KP972 on free radical. Adv. in Clin. Exp. Med. 2009 , 18, 6, 551-557.

2.  Sawicka E., Długosz A., Jędrzejczyk J:   Antioxidative Enzyme Activities After Exposure to KP972 and Cisplatin. Adv. in Clin. Exp. Med. 2011, 20,5,591-597.

3. Chirino Y., Pedraza-Chaverri J.: Role of oxidative and nitrosative stress in cisplatin-   induced nephrotoxicity. Exp. Toxicol. Pathol., 2009, 61, 223-242.

4. Maliakel D., Kagiya T., Krishnan Ch., Nair K.: Prevention od cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and α-tocopherol. Exp. Toxicol. Pathol., 2008, 60, 521-527.

5.    Sawicka E., Długosz A., Średnicka D.:    Działanie łączne wyciągu z tarczycy bajkalskiej i koenzymu Q10 w stresie oksydacyjnym wywołanym związkami chromu.  Environmental Medicine 2010, 13(1), 72-77.

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