科拉维酮可改善 7,12-二甲基苯并蒽诱导的乳腺损伤。

Kolaviron Ameliorates 7, 12-Dimethylbenzanthracene - Induced Mammary Damage.

机构信息

Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria.

Department of Pharmacology, University of the Free State, Bloemfontein 9300, South Africa.

出版信息

Anticancer Agents Med Chem. 2022;22(1):181-192. doi: 10.2174/1871520621666210322101232.

DOI:10.2174/1871520621666210322101232

PMID:34225638

Abstract

BACKGROUND

Kolaviron (KV) is a flavonoid-rich portion obtained from Garcinia kola seeds with a number of reported pharmacological effects. However, its ameliorative effects on 7,12-Dimethylbenzanthracene (DMBA)-induced mammary damage has not been fully investigated, despite the reported use of the seeds in the treatment of inflammatory related disorders.

OBJECTIVE

To evaluate the ameliorative effects of KV on DMBA-induced mammary damage in female Wistar rats.

METHODS

Forty-nine (49) female Wistar rats were randomly assigned into seven groups of seven rats each. DMBA was administered orally to rats in five of the groups as a single dose of 80 mg/kg body wt while the remaining two groups received the vehicle. The rats were palpated weekly for 3 months to monitor tumor formation. After 3 months of DMBA administration, 1 ml of blood was collected to assay for estrogen receptor- α (ER-α) level. Thereafter, the vehicle (dimethyl sulfoxide) was daily administered to the negative control and positive control groups for the 14 days duration of the experiment while three groups were each given a daily oral dose of 50, 100, and 200 mg/kg body wt of KV for the duration of the experiment. The last DMBA-induced group received 10 mg/kg body wt of the standard drug tamoxifen twice a week, and the remaining DMBA-free group received 200 mg/kg body wt KV. Subsequently, the animals were humanely sacrificed, and ER-α, sialic acids, sialidase, sialyltransferase levels were assayed in blood and mammary tissues followed by histopathological examinations.

RESULTS

Significantly higher levels of estrogen receptor-α (ER-α), formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased sialylation were detected in DMBA-induced rats. Treatment with KV at 50, 100, and 200 mg/kg body weight resulted in a significant (p<0.05) decrease in ER-α level, free serum sialic acid (21.1%), the total sialic acid level of the mammary tissue (21.57%), sialyltransferase activity (30.83%) as well as mRNA level of the sialyltransferase gene (ST3Gal1) were observed after KV interventions.

CONCLUSION

The findings suggest that KV could be further explored in targeting DMBA-induced mammary damage implicated in mammary carcinogenesis.

摘要

背景

科拉维酮（KV）是从可乐果种子中提取的富含类黄酮的部分，具有多种已报道的药理作用。然而，尽管有报道称该种子可用于治疗炎症相关疾病，但它对 7,12-二甲基苯并蒽（DMBA）诱导的乳腺损伤的改善作用尚未得到充分研究。

目的

评估 KV 对 DMBA 诱导的雌性 Wistar 大鼠乳腺损伤的改善作用。

方法

将 49 只雌性 Wistar 大鼠随机分为 7 组，每组 7 只。5 组大鼠口服给予 80mg/kg 体重的 DMBA 作为单次剂量，其余 2 组给予载体。大鼠每周进行触诊，监测 3 个月肿瘤形成情况。DMBA 给药 3 个月后，采集 1ml 血液检测雌激素受体-α（ER-α）水平。此后，阴性对照和阳性对照组每天给予载体（二甲基亚砜），持续 14 天，而另外 3 组分别给予 50、100 和 200mg/kg 体重的 KV 每天口服剂量，持续 14 天。最后一组 DMBA 诱导组每周两次给予 10mg/kg 体重的标准药物他莫昔芬，其余 DMBA 无诱导组给予 200mg/kg 体重的 KV。随后，将动物人道处死，检测血液和乳腺组织中的 ER-α、唾液酸、唾液酸酶、唾液酸转移酶水平，并进行组织病理学检查。

结果

在 DMBA 诱导的大鼠中，检测到雌激素受体-α（ER-α）水平显著升高，形成小叶肿瘤细胞、上皮增生、淋巴细胞浸润和唾液酸化增加。用 50、100 和 200mg/kg 体重的 KV 治疗可显著降低 ER-α水平（p<0.05），游离血清唾液酸（21.1%）、乳腺组织总唾液酸水平（21.57%）、唾液酸转移酶活性（30.83%）以及唾液酸转移酶基因（ST3Gal1）的 mRNA 水平也显著降低。