Sanative Effect of Resveratrol-ZnO Nano-conjugate in DMBA Induced Ovarian Cancer in Murine Model

Background: 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 RSVZnO 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 Intra Peritoneal (IP) injection at 200 mg/kg and 400 mg/kg bw 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, 200 mg/kg body weight for 28 days. At the end of the study, the animals were sacrificed and effect of RSV-ZnO nano-drug on body and organ weight and hematological biochemical parameters and histopathological findings was evaluated. DMBA was used as inducing agent to develop ovarian cancer. Rats were treated by DMBA (50 mg/kg bw) via IP route once a week upto 3 week 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 bw by IP) weekly for one month. After that, we sacrificed the animals and taken out the ovaries for histopathology for tumour 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 tumour. Besides, in acute and sub-acute toxicity study, it exhibited no untoward effects in animals.

Conclusion: The findings demonstrated that resveratrol ZnO nano-conjugate drug is safe and may be used for the treatment of ovarian cancer causing more efficacy and less toxicities.

Author(s): Soumendra Darbarb*, Ritwik Maity, Santasree Mazumder and Mahamuda Khatun

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