Verma Ashish S, Singh Anchal, Mallick Priyadarshini, Dwivedi Premendra D
Pro-Vice-Chancellor, Jadavpur University, Kolkata, West Bengal, India.
Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
J Pharm Bioallied Sci. 2019 Jan-Mar;11(1):23-32. doi: 10.4103/jpbs.JPBS_108_18.
Previously, we have reported the amelioration of ad-AF induced hepatotoxicity with the exogenous supplementation of glutathione (GSH) without compromising the anti-tumor effect of ad-AF in ascites tumor model of mice with transplantable Ehrlich's Ascites Tumor cells. Cellular uptake of glutathione (GSH) has its own limitations, therefore exogenous supplementation of L-cysteine (Cys) was tried to reduce the toxicity of ad-AF by providing -SH contents without compromising the anti-tumor property of adsorbed ascites fluid (ad-AF).
A significant increase in mean survival time (MST) of tumor bearing mice from 18.1 days to 32.9 days with exogenous supplementation of Cys was observed. Cys supplementation did not alter decline in body-weight gain, tumor cell counts as well as decrease in the viability of tumor cells in ascites tumor bearing animals. Similarly, Cys has been helpful to restore the hepatic -SH contents upto the levels of -SH content in tumor control group. The exogenous supplementation of Cys along with ad-AF has been helpful to restore the decline in the activities of phase-I and enhanced levels of glutathione-S-transferase (GST). The changes in the activities of different enzymes of phase-I and phase-II indicate the reduction in toxic insult induced by the therapeutic material (ad-AF). However, ad-AF treatment could not prevent tumor bearers from natural death due to tumor progression but significantly reduced the rate of tumor progression.
Our study suggests that exogenous supplementation of Cys alongwith ad-AF could have a potential to be developed as a modality for the treatment of ascites tumor at least at experimental level.
此前,我们报道了在可移植艾氏腹水瘤细胞的小鼠腹水瘤模型中,外源性补充谷胱甘肽(GSH)可改善腺病毒介导的腹水(ad-AF)诱导的肝毒性,且不影响ad-AF的抗肿瘤作用。谷胱甘肽(GSH)的细胞摄取存在自身局限性,因此尝试外源性补充L-半胱氨酸(Cys),通过提供巯基含量来降低ad-AF的毒性,同时不损害吸附腹水(ad-AF)的抗肿瘤特性。
观察到外源性补充Cys后,荷瘤小鼠的平均生存时间(MST)从18.1天显著增加到32.9天。补充Cys并未改变荷腹水瘤动物体重增加的下降、肿瘤细胞计数以及腹水肿瘤细胞活力的降低。同样,Cys有助于将肝脏巯基含量恢复到肿瘤对照组的巯基含量水平。外源性补充Cys与ad-AF一起有助于恢复I相酶活性的下降以及谷胱甘肽-S-转移酶(GST)水平的升高。I相和II相不同酶活性的变化表明治疗物质(ad-AF)诱导的毒性损伤有所减少。然而,ad-AF治疗无法阻止荷瘤小鼠因肿瘤进展而自然死亡,但显著降低了肿瘤进展的速度。
我们的研究表明,外源性补充Cys与ad-AF一起至少在实验水平上有可能被开发为一种治疗腹水瘤的方法。