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,Letteria Minutoli,Giuseppe Santoro,Natasha Irrera,Herbert Ryan Marini,Michele Navarra,Giovanni Pallio,Domenico Puzzolo,Jose Freni,Francesco Squadrito,Antonio Micali,Alessandro Maugeri

doi:10.3390/biomedicines9121797

Santa Cirmi, Letteria Minutoli + Show 10 more

Open Access

https://doi.org/10.3390/biomedicines9121797

Copy DOI

Abstract

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.

Highlights

Levels of urea nitrogen and creatinine are often employed as biomarkers for the evaluation of kidney function
No significant differences in urea nitrogen and creatinine levels were observed in the serum of all control groups; only one value is indicated for controls (Table 2)
In CdCl2 -challenged animals co-treated with all tested nutraceuticals, urea nitrogen and creatinine levels were lower than CdCl2 + vehicle group (p < 0.05), being similar to control mice in those treated with bergamot juice extract (BJe) at the dose of 40 mg/kg and with both associations

Summary

Introduction

Cadmium (Cd) is a non-essential metal present at position 7 on the substance priority list of the Agency for Toxic Substances and Disease Registry (ATSDR 2019). It is an environmental and industrial toxicant, derived from incineration, refining, mining, and fossil fuel combustion. Environmental exposure to Cd is progressively increasing, owing to the wide use of Cd-containing goods in industrialized countries, and it represents a major public health risk due to its non-biodegradability as well as to its long biological half-life (10–30 years) [1]. Environmental Cd may accumulate in many organs, such as liver, lung, testes, and bones. The main target of Cd is considered the kidney, the proximal

Methods

Results

Discussion

Conclusion