Plausible effect of hesperetin and nano-hesperetin against bisphenol-A induced hepatoxicity in a rat model

Bisphenol A(BPA) is a non-persistent, anthropic compound and continues to be ubiquitous in the environment. Since BPA is estrogenic in nature, its exposure induces adverse cellular responses associated with oxidative stress and inflammation. Hesperetin, a major flavonoid present in lemons and sweet oranges exhibits a broad spectrum of pharmacological effects attributed to its potent anti-inflammatory and antioxidant status. The current study reports the 'green' synthesis of nano hesperetin (NHsp) followed by characterization that included; Fourier Transform Infrared spectroscopy (FTIR), X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). In accordance with the findings, the mean size of the synthesized nanoparticles was 139.9 nm with a PDI of 0.362. The morphotype was primarily spherical and rod shaped. This was followed by a comparative assessment of the ameliorative efficacy of bulk and nano hesperetin against BPA-induced hepatotoxicity in rat. The findings showed that post-exposure to 250 mg/ kg of BPA for 21 days significantly enhanced the pro-inflammatory cytokines (IL-6, IL-8, IL-1 beta, TNF-alpha), in the serum with a concomitant upregulation in the mRNA expression of Nrf 2(Nuclear factor erythroid 2-related factor) factor in the liver. Treatment with both bulk hesperetin (Hst) and nano hesperetin (NHst) reduced the levels of cytokines and expression of hepatic Nrf2 factor. This was paralleled by the modulatory effects on the histology of liver and kidney which were reversed on treatment. Taken together, the nano hesperetin was more efficacious in alleviating the BPA-induced toxicity. Thus,hesperetin and its nano formulation could be potentially promising nutraceuticals in medicine and industry.