Tangeretin, a citrus flavonoid attenuates oxidative stress and protects hepatocellular architecture in rats with 7, 12 - dimethylbenz(a)anthracene induced experimental mammary carcinoma

• Tangeretin protects hepatocellular architecture in rats with DMBA induced experimental breast cancer.
• Tangeretin has been shown to exert chemotherapeutic and nephroprotective effect in DMBA induced mammary carcinogenesis.
• Tangeretin attenuates DMBA induced oxidative stress in the liver via Nrf2/Keap1 and AhR signalling pathways.
• Tangeretin modulates the DMBA induced inflammatory cytokines in the liver.
• Tangeretin reduces the DMBA induced DNA damage in the liver.

The modulatory effect of tangeretin on the oxidative damage induced by DMBA in the hepatic tissue of mammary tumour bearing rat was investigated. Breast cancer was induced by “air pouch technique” with a single dose of 25 mg/kg of 7, 12 - dimethylbenz[a]anthracene (DMBA). Tangeretin (50 mg/kg body weight) was administered orally for four weeks. The hepatoprotective nature of tangeretin was evidenced from the altered levels of liver marker enzymes, oxidative stress markers, histopathological and ultrastructural analysis in the liver tissues of control and experimental animals. Further, tangeretin treatment notably normalized the hepatic expression of aryl hydrocarbon receptor (AhR) and Nrf2/Keap1 proteins in the DMBA induced rats which were substantiated by polymerase chain reaction (PCR), western blotting, immunofluorescence and immunohistochemical analysis. Electrophoretic mobility shift assay (EMSA) proved that tangeretin influenced the binding of Nrf2 on the HO-1 promoter, thereby exerting antioxidant effect. The Comet and DNA fragmentation analysis also showed that tangeretin reduced the DMBA induced DNA damage in the liver.