Abstract

Garcinia kola seed is used to manage liver diseases in ethnomedicine. However, there is limited information on its role in Cisplatin (CIS)-induced toxicity. Here, we investigated the potential of hexane extract of Garcinia kola (HEGK) in lessening CIS-induced hepatorenal- and gene- toxicity. Male mice (22 ± 3 g) randomly assigned into groups (n = 5) were treated for five days: Corn oil only, HEGK (200 mg/kg), CIS (20 mg/kg; i.p; 48-hours), CIS + HEGK (100 mg/kg), CIS + HEGK (200 mg/kg), CIS + Quercetin (25 mg/kg), and Quercetin(25 mg/kg). Corn oil, HEGK, and Quercetin were administered daily by gavage. GC-MS revealed the presence of 9,19-Cyclolanost-24-en-3-ol as the most abundant component in HEGK, with an LC₅₀ of 1023 µg/mL. HEGK significantly (p < 0.05) scavenged DPPH, inhibited lipid peroxidation and exhibited reducing activity dose-dependently. CIS treatment increased (p < 0.05) urinary albumin and creatinine by 18 and 56%, respectively, serum levels of total bilirubin, creatinine, and hepatic transaminases, while albumin decreased (p < 0.05) by 57%. CIS treatment increased renal and hepatic malondialdehyde (MDA) levels by 67 and 70% individually, while the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels were decreased (p < 0.05). Furthermore CIS-induced the formation of mononucleated polychromatic erythrocytes (mnPCEs) 150% in the bone marrow of mice. Histology revealed necrosis of hepatocytes, congestion of renal interstitial vessel, and hyperplasia of the Kupffer cells. Pretreatment with HEGK reduced the levels of MDA, mnPCEs, and increased the activities of antioxidant enzymes and restored GSH to levels comparable in control mice. Taken together, HEGK ameliorated CIS-toxicity via the activation of the antioxidative pathways and mitigated genotoxicity by mitigating mnPCEs formation in mice.

摘要

藤黄可乐种子用于治疗民族医学中的肝脏疾病。然而，关于其在顺铂 (CIS) 诱导的毒性中的作用的信息有限。在这里，我们研究了藤黄果己烷提取物(HEGK) 在减轻 CIS 诱导的肝肾和基因毒性方面的潜力。雄性小鼠 (22 ± 3 g) 随机分组 ( n  = 5) 治疗 5 天：仅玉米油、HEGK (200 mg/kg)、CIS (20 mg/kg; ip; 48 小时)、CIS + HEGK (100 mg/kg)、CIS + HEGK (200 mg/kg)、CIS + 槲皮素 (25 mg/kg) 和槲皮素 (25 mg/kg)。玉米油、HEGK 和槲皮素每天通过管饲法给药。GC-MS 显示 9,19-Cyclolanost-24-en-3-ol 是 HEGK 中最丰富的成分，LC ₅₀1023 µg/mL。HEGK 显着 ( p  < 0.05) 清除 DPPH，抑制脂质过氧化并表现出剂量依赖性降低活性。CIS 治疗使 尿白蛋白和肌酐分别增加 18% 和 56%，血清总胆红素、肌酐和肝转氨酶水平分别增加 (p < 0.05)，而白蛋白降低了 ( p <  0.05) 57%。CIS 治疗使肾脏和肝脏丙二醛 (MDA) 水平分别增加了 67% 和 70%，而谷胱甘肽过氧化物酶 (GPx)、超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT) 和还原型谷胱甘肽 (GSH) 的活性降低了 ( p < 0.05)。此外，CIS 诱导小鼠骨髓中 150% 的单核多染性红细胞 (mnPCE) 形成。组织学显示肝细胞坏死、肾间质血管充血和枯否细胞增生。HEGK 预处理降低了 MDA、mnPCE 的水平，并增加了抗氧化酶的活性，并将 GSH 恢复到与对照小鼠相当的水平。总之，HEGK 通过激活抗氧化途径来改善 CIS 毒性，并通过减轻小鼠中 mnPCE 的形成来减轻遗传毒性。