Kolaviron pre‐treatment suppresses 7, 12 dimethylbenzanthracene‐induced alterations in estrogen receptor‐α, CYP 1A1, oxidative stress and inflammation in female Wistar rats

• Published in: Journal of food biochemistry Vol. 46; no. 2; pp. e13984 - n/a
• Main Authors: Attah, O. C., Umar, I. A., Ameh, D. A., Forcados, G. E., Muhammad, A., Sani, I.
• Format: Journal Article
• Language: English
• Published: United States 01.02.2022
• Subjects: 7, 12‐dimethylbenzanthracene; Animals; chemoprevention; Cytochrome P-450 CYP1A1 - pharmacology; Female; Flavonoids; inflammation; Inflammation - drug therapy; kolaviron; mammary neoplasia; Oxidative Stress; Plant Extracts - pharmacology; Rats; Rats, Wistar; Receptors, Estrogen; 7, 12-dimethylbenzanthracene; kolaviron; chemoprevention; inflammation; mammary neoplasia; oxidative stress
• ISSN: 0145-8884; 1745-4514
• DOI: 10.1111/jfbc.13984

Due to the need to develop locally available, cheaper, and efficacious treatment regimens for breast cancer, the chemopreventive effect of kolaviron (KV), an extract of Garcinia kola seeds was examined. Fifty (50) female Wistar rats (120–180 g) were assigned to five groups (control group, 7, 12 dimethylbenzanthracene [DMBA] groups, tamoxifen group) of 10 rats each. They were pre‐treated with KV thrice a week for four weeks except control. Estrogen receptor‐α (ER‐α) levels were determined in the pre‐treated rats before induction of mammary carcinogenesis. After the four weeks pre‐treatment period, 80 mg/kg of DMBA was used for induction. A hundred and fifty (150) days after induction, the rats were sacrificed humanely. Significantly higher levels of ER‐α, formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, increased cytokines (interleukin‐6 [IL‐6] and tumor necrosis factor‐α [TNF‐α]), CYP1A1 activity and malondialdehyde (MDA) with a corresponding decrease in superoxide dismutase (SOD), catalase and glutathione peroxidase were observed in DMBA‐induced rats. Pre‐treatment with KV at 200 mg/kg body weight significantly (p < .05) decreased ER‐α levels by 19.01% and 37.52%, [IL‐6] by 36.37% and 20.55%, TNF‐α by 42.2% and 12.33% in serum and mammary tissue respectively. Also, a significant (p < .05) decrease in serum CYP1A1 activity, MDA with concomitant increase in SOD, catalase and glutathione peroxidase activities were observed in serum and mammary tissue respectively. Collectively, the results suggest that KV could be further explored in targeting chemoprevention of DMBA‐induced mammary damage. Practical applications Garcinia kola is widely cultivated in West and Central Africa with kolaviron (KV) as its major constituents. The seeds which have a bitter astringent taste are widely consumed by people in the region. Locals claim that consumption of the seeds provides relief for the management of several ailments including cancer. However, scientific investigations that provide a basis for these claims are still needed. This study provides evidence that points to the ameliorative potential of KV on breast cancer model. The results will be beneficial to local communities who hitherto had no knowledge on the potential of G. kola in chemoprevention. The results from this study will also attract further research attention from the international scientific community to examine the anti‐cancer benefits of G. kola. This will also be beneficial to the global community due to the increasing number of breast cancer cases recorded annually. Administration of 7,12‐dimethylbenzanthracene (DMBA) to female wistar rats led to induction of CYP1A1 which bio‐transformed it to carcinogenic intermediate dihydrodiol epoxide. Dihydrodiol epoxide could form adducts with DNA and proteins leading to oxidative damage characterised by stress and inflammation via elevation of estrogen receptor‐α and pro‐inflammatory cytokines. However, kolaviron pre‐treatment suppresses DMBAinduced alterations in estrogen receptor‐α, CYP1A1, oxidative stress and inflammation in female Wistar rats.