Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benz{a}anthracene (DMBA) induced breast cancer rats

<p>Abstract</p> <p>Background</p> <p>Antineoplastic drug cisplatin remains the drug of choice for various solid tumours including breast cancer. But dose dependent nephrotoxicity is the major drawback in majority of platinum based chemotherapy regimens. Recent reports have shown that inflammatory pathways are the main offender for cisplatin induced nephrotoxicity. The present study was undertaken to assess the effect of rosiglitazone, a PPARγ agonist and an anti-inflammatory agent, on cisplatin induced nephrotoxicity, and its anticancer activity in DMBA induced breast cancer rats.</p> <p>Methods</p> <p>Mammary tumours were induced in female Sprague-Dawley rats by feeding orally with dimethylbenz [a]anthracene (DMBA) (60 mg/kg). Cisplatin induced nephropathy was assessed by measurements of blood urea nitrogen, albumin and creatinine levels. Posttranslational modifications of histone H3, mitogen-activated protein (MAP) kinase p38 expression and PPAR-γ expression were examined by western blotting.</p> <p>Results</p> <p>Our data shows involvement of TNF-α in preventing cisplatin induced nephrotoxicity by rosiglitazone. Rosiglitazone pre-treatment to cisplatin increases the expression of p38, PPAR-γ in mammary tumours and shows maximum tumour reduction. Furthermore, cisplatin induced changes in histone acetylation, phosphorylation and methylation of histone H3 in mammary tumours was ameliorated by pre-treatment of rosiglitazone. Suggesting, PPAR-γ directly or indirectly alters aberrant gene expression in mammary tumours by changing histone modifications.</p> <p>Conclusion</p> <p>To best of our knowledge this is the first report which shows that pre-treatment of rosiglitazone synergizes the anticancer activity of cisplatin and minimizes cisplatin induced nephrotoxicity in DMBA induced breast cancer.</p

Functional foods as source of bioactive principles. Some marked examples

Functional foods are those that have a beneficial effect on health beyond the basic function of nutrition, helping to promote better health conditions and to reduce the risk of various diseases. This concept was created in Japan in the 1980s and is widely used around the world. The regulation of these products is made by different authorities and has not been defined yet in many countries. The field of food production has increased and changed considerably in the last decades, since the consumers believe that foods, besides satisfy hunger and to provide necessary nutrients for humans, also contribute directly to improve their health conditions. The present chapter will focus with marked examples the main categories of functional foods and respective therapeutic potential (cardioprotective, hepatoprotective, hypolipidemic, antioxidant, anticancer, anti-inflammatory properties, etc.) as well as the active principles responsible for the medicinal properties (flavonoids, alkaloids, terpenes, etc.), including curcuma, garlic, olive oil, grape, broccoli, and probiotic, among others