Preliminary investigation of organ-protective effects of fullerenol in vivo in acute toxicity during doxorubicin therapy in healthy pigs

Rade Injac, Aleksandar Djordjevic, Borut Strukelj
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Abstract

Abstract Objectives The potential protective effect of fullerenol C60(OH)24, a strong antioxidant, was investigated at a single dose of 25 mg/kg, administered orally (per os; p.o.) and intraperitoneally (i.p.), in the liver, lung, kidney, heart, and spleen of healthy pigs, prior to doxorubicin-induced toxicity at a single i.p. dose of 10 mg/kg. Methods We used the F1 generation of an in vivo pig model (whose parents were Swedish Landrace and Large Yorkshire), to explore whether fullerenol, administered 6 h for p.o. and 30 min for i.p. prior to doxorubicin treatment, could protect organs against damage caused by oxidative stress. Key findings According to the macroscopic, hematological, biochemical, and physiological results, fullerenol exerted a potential protective effect on all investigated organs (heart, liver, lung, spleen, and kidney) in pigs after i.p. administration. However, the results from fullerenol p.o. administration were inconclusive, therefore warranting further investigation. Conclusions Fullerenol at a low dose of 25 mg/kg demonstrated satisfactory organ protection against doxorubicin-induced toxicity in healthy pigs after i.p. injection, However, additional follow-up studies in pig models of cancer and with longer doxorubicin and fullerenol treatment periods would be required to further delineate the optimal and clinically-relevant conditions for fullerenol administration.
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健康猪阿霉素急性毒性治疗中富勒烯醇体内器官保护作用的初步研究
目的研究强抗氧化剂富勒烯醇C60(OH)24单次给药(25 mg/kg)的潜在保护作用。在单次口服剂量为10mg /kg的阿霉素引起毒性之前,在健康猪的肝脏、肺、肾脏、心脏和脾脏中进行腹腔注射(i.p.)。方法采用F1代在体猪模型(亲本为瑞典长白猪和大约克猪),探讨在阿霉素治疗前分别给予6 h po和30 min ig的富勒烯醇是否能保护器官免受氧化应激损伤。根据宏观、血液学、生化和生理学结果,富勒烯醇在给药后对猪的所有器官(心、肝、肺、脾和肾)都有潜在的保护作用。然而,富勒烯醇口服的结果是不确定的,因此需要进一步的调查。结论低剂量(25 mg/kg)的富勒烯醇在健康猪腹腔注射后对多柔比星诱导的器官毒性具有满意的保护作用,然而,需要对猪癌症模型进行进一步的随访研究,并延长多柔比星和富勒烯醇的治疗时间,以进一步确定富勒烯醇给药的最佳条件和临床相关条件。
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