Afsar Tayyaba, Razak Suhail, Almajwal Ali, Rashid Khan Muhammad
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
BMC Complement Altern Med. 2017 Jun 12;17(1):307. doi: 10.1186/s12906-017-1824-y.
Cisplatin (CP) is recommended as a first-line chemotherapeutic agent for solid tumors, however its usage outcomes in severe adverse effects. Acacia hydaspica possesses various phytochemicals and pharmacological activities. The current study aimed to investigate the protective effect of A. hydaspica ethyl acetate extract (AHE) against CP induced aberrations in lipid profile and hepatotoxicity.
Rats were randomly separated into six groups (n = 6). Group 1 (control) received distilled water orally for 21 days. Groups 2 (CP control) received a single dose of CP (7.5 mg/kg bw, i.p) on day 16, group 3 (Plant control) received AHE (400 mg/kg b.w, oral) for 21 days, group 4 (post treated group); CP received on day 16 and AHE (400 mg/kg b.w/day, p.o.) was administered after CP till day 21, Group 5 (pretreated group) received AHE (400 mg/kg b.w/day, p.o.) for 21 days and CP (7.5 mg/kg b.w., i.p.) on day 16, group 6 (Silymarin + CP) received 100 mg/kg b.w., p.o. (11 doses/21 days) and CP (7.5 mg/kg b.w., i.p.) on day 16. Lipid profile, liver functional tests, oxidative stress markers, antioxidant enzymes status and histopathological changes were examined.
The present study revealed that CP caused body weights loss and increase liver index. CP significantly increased serum total lipid, triglycerides and LDL-cholesterol levels. Conversely, it significantly decreased serum HDL-cholesterol level. CP induced marked deteriorations in serum liver function biomarkers, reduced antioxidant enzymes in tissue, while elevated tissue oxidative stress markers along with morphological injuries compared to control rats. Treatment with AHE ameliorated CP induced alterations in lipid profile, serum ALT, AST, ALP and total bilirubin levels and liver weight. Furthermore AHE treatment improved the total protein and antioxidant enzymes levels while decreased the level of MDA, HO, and NO. The altered parameters were returned to the control level with AHE pretreatment. Histopathological analysis also supported the biochemical findings. Pretreatment seems to be more effective compared to post treatment indicating protective effect.
These results reveal that treatment of AHE may be useful in the prevention of CP induced hepatotoxicity due to its antioxidant potential and polyphenolic constituents.
顺铂（CP）被推荐作为实体瘤的一线化疗药物，然而其使用会导致严重的不良反应。阿拉伯胶具有多种植物化学成分和药理活性。本研究旨在探讨阿拉伯胶水提取物（AHE）对顺铂诱导的脂质谱异常和肝毒性的保护作用。
将大鼠随机分为六组（n = 6）。第1组（对照组）口服蒸馏水21天。第2组（CP对照组）在第16天接受单次剂量的顺铂（7.5 mg/kg体重，腹腔注射），第3组（植物对照组）口服AHE（400 mg/kg体重）21天，第4组（后处理组）在第16天接受顺铂，之后直至第21天给予AHE（400 mg/kg体重/天，口服），第5组（预处理组）口服AHE（400 mg/kg体重/天）21天，并在第16天接受顺铂（7.5 mg/kg体重，腹腔注射），第6组（水飞蓟宾 + CP组）口服100 mg/kg体重（21天内11剂）并在第16天接受顺铂（7.5 mg/kg体重，腹腔注射）。检测脂质谱、肝功能测试、氧化应激标志物、抗氧化酶状态和组织病理学变化。
本研究表明，顺铂导致体重减轻并增加肝脏指数。顺铂显著提高血清总脂质、甘油三酯和低密度脂蛋白胆固醇水平。相反，它显著降低血清高密度脂蛋白胆固醇水平。与对照大鼠相比，顺铂导致血清肝功能生物标志物显著恶化，组织中的抗氧化酶减少，而组织氧化应激标志物升高以及出现形态学损伤。AHE治疗改善了顺铂诱导的脂质谱、血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶和总胆红素水平以及肝脏重量的改变。此外，AHE治疗提高了总蛋白和抗氧化酶水平，同时降低了丙二醛、羟基自由基和一氧化氮水平。经AHE预处理后，改变的参数恢复到对照水平。组织病理学分析也支持了生化结果。预处理似乎比后处理更有效，表明具有保护作用。
这些结果表明，由于其抗氧化潜力和多酚成分，AHE治疗可能有助于预防顺铂诱导的肝毒性。
