Safety and Efficacy of Resveratrol-ZnO nanoconjugate in DMBA-induced ovarian cancer in murine model

Resveratrol (3,5,4-trihydroxy-transstilbene), a natural phytoalexin is well known for its anticancer and chemo-preventive effect. To overcome stability and solubility issue of Resveratrol (RSV), a conjugation of RSV with ZnO nanoparticles was prepared to improve the efficacy and reduce the toxicity. Thus objective of the present study was to evaluate the potential effect of RSV-ZnO nano-conjugate in DMBA-induced ovarian cancer in a defined rat model. The acute and sub-acute toxicity was carried as per OECD guidelines 423 and 407, respectively. In the acute toxicity study, nano-conjugate drug was administered via single Intraperitoneally (IP) injection at 200 mg/kg and 400 mg/kg body weight doses in female albino Wistar rats while in sub-acute toxicity study, female Wistar rats was administered daily IP injection of 50 mg/kg, 100 mg/kg and 200 mg/kg body weight for 28 days. At the end of the study, the animals were sacrificed and evaluate the effect of RSV-ZnO nano-drug on body and organ weight and hematological biochemical parameters and histopathological findings. DMBA was used as inducing agent to develop ovarian cancer. Rats were treated by DMBA (50 mg/kg body weight) via IP route once a week up to 3 weeks and kept animals for 3 months for development and progression of carcinogenesis in ovary. After 3 months, we treated the induced animals by RSV-ZnO nano-conjugate in three different doses (50 mg/kg, 100 mg/kg and 150 mg/kg body weight by IP) weekly for one month. After that, we sacrificed the animals and taken out the ovaries for histopathology for tumor subtyping and immunohistochemistry to evaluate the markers such as CA125, CK7, Vimentin. RSV-ZnO nano-conjugate showed significant reduction of expression of cancer bio-markers and size of tumor. Besides, in acute and sub-acute toxicity study, it exhibited no untoward effects in animals. The findings demonstrated that RSV ZnO nano-conjugate drug is safe and may be used for the treatment of ovarian cancer with more efficacies and less toxicities.