Bagchi D, Ray S D, Patel D, Bagchi M
Creighton University School of Pharmacy and Allied Health Professions, Omaha, Nebraska, USA.
Drugs Exp Clin Res. 2001;27(1):3-15.
Grape seed proanthocyanidins have been demonstrated to exhibit a broad spectrum of pharmacological, therapeutic and chemoprotective properties. In our previous studies, IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) demonstrated excellent concentration- and dose-dependent free radical scavenging abilities in both in vitro and in vivo models and provided significantly better protection than vitamins C, E and beta-carotene. GSPE demonstrated significant cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mucosal cells and macrophage J774A.1 cells. In this study, the bioavailability and protective ability of GSPE were examined against acetaminophen-induced hepatoxicity, amiodarone-induced pulmonary toxicity, doxorubicin-induced cardiotoxicity, cadmium chloride-induced nephrotoxicity, dimethylnitrosamine-induced spleenotoxicity and O-ethyl-S,S-dipropyl phosphorodithioate (MOCAP)-induced neurotoxicity in mice. In each experiment, half of the test animals were orally fed GSPE for 7-10 days prior to drug/chemical exposure, while the other half received no GSPE. Parameters of analysis included changes in serum chemistry [alanine amino-transferase (ALT), blood urea nitrogen and creatine kinase], histopathology and integrity of genomic DNA. The results indicated that GSPE preexposure prior to the drugs/chemicals such as acetaminophen, amiodarone, doxorubicin, cadmium chloride or dimethylnitrosamine treatment, provided near complete protection in terms of serum chemistry changes (ALT, blood urea nitrogen and creatine kinase) and inhibition of both forms of cell death, e.g., apoptosis and necrosis. DNA damage in various tissues triggered by these agents was significantly reduced. Histopathological examination of the organs evaluated reflected similar patterns to those of the serum chemistry and DNA results. MOCAP exposure showed symptoms of severe neurotoxicity coupled with serum chemistry changes in the absence of any significant genomic change or brain pathology. GSPE afforded only partial protection in the brain tissue. These results suggest that GSPE exposure is bioavailable and provides significant multiorgan protection against drug- and chemical-induced toxic assaults.
葡萄籽原花青素已被证明具有广泛的药理、治疗和化学保护特性。在我们之前的研究中，IH636葡萄籽原花青素提取物（GSPE，商品名为ActiVin）在体外和体内模型中均表现出优异的浓度和剂量依赖性自由基清除能力，且比维生素C、E和β-胡萝卜素提供了显著更好的保护作用。GSPE对人乳腺癌、肺癌和胃腺癌细胞表现出显著的细胞毒性，同时增强正常人胃黏膜细胞和巨噬细胞J774A.1细胞的生长和活力。在本研究中，检测了GSPE对小鼠对乙酰氨基酚诱导的肝毒性、胺碘酮诱导的肺毒性、阿霉素诱导的心脏毒性、氯化镉诱导的肾毒性、二甲基亚硝胺诱导的脾毒性以及O-乙基-S,S-二丙基二硫代磷酸酯（MOCAP）诱导的神经毒性的生物利用度和保护能力。在每个实验中，一半的实验动物在药物/化学物质暴露前口服GSPE 7至10天，而另一半不接受GSPE。分析参数包括血清化学变化[丙氨酸转氨酶（ALT）、血尿素氮和肌酸激酶]、组织病理学以及基因组DNA的完整性。结果表明，在对乙酰氨基酚、胺碘酮、阿霉素、氯化镉或二甲基亚硝胺等药物/化学物质处理之前预先暴露GSPE，在血清化学变化（ALT、血尿素氮和肌酸激酶）以及抑制两种细胞死亡形式（即凋亡和坏死）方面提供了近乎完全的保护。这些药物引发的各种组织中的DNA损伤显著减少。对所评估器官的组织病理学检查反映出与血清化学和DNA结果相似的模式。MOCAP暴露显示出严重神经毒性症状以及血清化学变化，而没有任何显著的基因组变化或脑部病理学改变。GSPE仅对脑组织提供部分保护。这些结果表明，暴露于GSPE具有生物利用度，并对药物和化学物质诱导的毒性攻击提供显著的多器官保护。
