Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard, (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
Life Sci. 2011 Sep 26;89(13-14):422-9. doi: 10.1016/j.lfs.2011.06.016. Epub 2011 Jul 7.
Glycyrrhizic acid (GA) is a main sweetening component of licorice roots and has been found to be associated with multiple therapeutic properties. In this study, we used GA as a protective agent against the clastogenic and nephrotoxic effects of cisplatin (CP).
Mice were given a prophylactic treatment of GA orally at doses of 75 and 150mg/kg body weight for seven consecutive days before the administration of a single intraperitoneal dose of CP at 7mg/kg body weight. The modulatory effects of GA on CP-induced nephrotoxicity and genotoxicity were investigated by assaying oxidative stress biomarkers, lipid peroxidation, serum kidney toxicity markers, DNA fragmentation, alkaline unwinding, and micronuclei and by histopathological examination of the kidneys.
A single intraperitoneal dose of cisplatin in mice enhanced renal lipid peroxidation, xanthine oxidase, and H(2)O(2) generation; depleted glutathione content, activities of the anti-oxidant enzymes glutathione peroxidase, glutathione reductase, catalase, glutathione-S-transferase and quinone reductase; induced DNA strand breaks and micronucleus formation (p<0.001); and majorly disrupted normal kidney architecture. Pretreatment with GA prevented oxidative stress by restoring the levels of antioxidant enzymes at both doses. A significant dose-dependent decrease in DNA fragmentation, micronucleus formation (p<0.05), and the kidney toxicity markers BUN (p<0.001), creatinine (p<0.01), and LDH (p<0.001) and restoration of normal kidney histology was observed.
Our study supports the claim that the phytochemical GA has the potential to attenuate the side effects of anticancer drug overdose.
甘草酸（GA）是甘草根中的主要甜味成分，已被发现与多种治疗特性有关。在这项研究中，我们使用 GA 作为保护剂，以对抗顺铂（CP）的致突变和肾毒性作用。
在单次腹腔内给予 CP 7mg/kg 体重之前，连续 7 天每天用 75 和 150mg/kg 体重的 GA 对小鼠进行口服预防性治疗。通过测定氧化应激生物标志物、脂质过氧化、血清肾毒性标志物、DNA 片段化、碱性解旋和微核以及肾组织病理学检查，研究 GA 对 CP 诱导的肾毒性和遗传毒性的调节作用。
单次腹腔内给予 CP 会增强小鼠肾脏的脂质过氧化、黄嘌呤氧化酶和 H₂O₂的产生；消耗谷胱甘肽含量、抗氧化酶谷胱甘肽过氧化物酶、谷胱甘肽还原酶、过氧化氢酶、谷胱甘肽-S-转移酶和醌还原酶的活性；诱导 DNA 链断裂和微核形成（p<0.001）；并主要破坏正常的肾脏结构。GA 的预处理通过在两种剂量下恢复抗氧化酶的水平来防止氧化应激。DNA 片段化、微核形成（p<0.05）和肾毒性标志物 BUN（p<0.001）、肌酐（p<0.01）和 LDH（p<0.001）的显著剂量依赖性降低以及正常肾组织学的恢复均观察到。
我们的研究支持了植物化学物质 GA 具有减轻抗癌药物过量副作用的潜力的说法。
