Cadmium-Induced Kidney Injury in Mice Is Counteracted by a Flavonoid-Rich Extract of Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, via the Enhancement of Different Defense Mechanisms
Santa Cirmi,
Alessandro Maugeri,
Antonio Micali,
Herbert Ryan Marini,
Domenico Puzzolo,
Giuseppe Santoro,
Jose Freni,
Francesco Squadrito,
Natasha Irrera,
Giovanni Pallio,
Michele Navarra,
Letteria Minutoli
Affiliations
Santa Cirmi
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Alessandro Maugeri
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Antonio Micali
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy
Herbert Ryan Marini
Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
Domenico Puzzolo
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy
Giuseppe Santoro
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy
Jose Freni
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy
Francesco Squadrito
Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
Natasha Irrera
Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
Giovanni Pallio
Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
Michele Navarra
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Letteria Minutoli
Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
Cadmium (Cd) represents a public health risk due to its non-biodegradability and long biological half-life. The main target of Cd is considered the kidney, where it accumulates. No effective treatment for Cd poisoning is available so that several therapeutic approaches were proposed to prevent damages after Cd exposure. We evaluated the effects of a flavonoid-rich extract of bergamot juice (BJe), alone or in association with curcumin (Cur) and resveratrol (Re), in the kidney of mice exposed to cadmium chloride (CdCl2). Male mice were administered with CdCl2 and treated with Cur, Re, or BJe alone or in combination for 14 days. The kidneys were processed for biochemical, structural and morphometric evaluation. Cd treatment significantly increased urea nitrogen and creatinine levels, along with tp53, Bax, Nos2 and Il1b mRNA, while reduced that of Bcl2, as well as glutathione (GSH) content and glutathione peroxidase (GPx) activity. Moreover, Cd caused damages to glomeruli and tubules, and increased Nrf2, Nqo1 and Hmox1 gene expression. Cur, Re and BJe at 40 mg/kg significantly improved all parameters, while BJe at 20 mg/kg showed a lower protective effect. After treatment with the associations of the three nutraceuticals, all parameters were close to normal, thus suggesting a new potential strategy in the protection of renal functions in subjects exposed to environmental toxicants.
