A Flavonoid-Rich Extract from Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, Shows Protective Effects in a Murine Model of Cadmium-Induced Testicular Injury.

Nadia Ferlazzo,Giovanni Pallio,Josè Freni,Michele Navarra,Santa Cirmi,Letteria Minutoli,Herbert Ryan Marini,Francesco Squadrito,Domenico Puzzolo,Giuseppe Santoro,Antonio Micali

doi:10.3390/ph14050386

Nadia Ferlazzo, Giovanni Pallio + Show 9 more

Open Access

https://doi.org/10.3390/ph14050386

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Abstract

It is known that cadmium damages testis structure and functionality. We examined the effects of nutraceuticals such as a flavonoid-rich extract of bergamot juice (BJe), alone or in association with curcumin (Cur) and resveratrol (Re), on mice testicular dysfunction caused by cadmium chloride (CdCl2). Controversial data on the protective effects of Cur and Re are available, while no evidence on the possible role of BJe exists. Adult male C57 BL/6J mice were administered with CdCl2 and treated with Cur, Re, or BJe alone or in combination for 14 days. Then, testes were removed and processed for molecular, structural, and immunohistochemical analyses. CdCl2 increased the mRNA of IL-1β, TNF-α, p53, and BAX while reduced that of Bcl-2 and induced tubular lesions and apoptosis of germinal cells. Cur, Re, and BJe at 40 mg/kg significantly improved all of these parameters and events, although BJe at 20 mg/kg showed a lower protective effect. The association of Cur, Re, and BJe at both doses of 50/20/20 and 100/20/40 mg/kg brought each parameter close to those of the control. Our results indicate that the nutraceuticals employed in this study and their associations exert a positive action against Cd-induced testicular injury, suggesting a possible protection of testis functionality in subjects exposed to environmental toxicants.

Highlights

Cadmium (Cd) is a nonessential transition metal without any physiological function in the human body, often considered a ubiquitous toxicant with carcinogenic activity
Ratio significantly lower than the control (Table 1). Both doses of Cur slightly increased these parameters with respect to those found in CdCl2 -injured mice that, remained significantly lower than the controls (Table 1)
In CdCl2 + Re treated mice, all parameters considered in this task showed a significant improvement in comparison to those assessed in CdCl2 -subjected mice (p < 0.05) as occurs with bergamot juice (BJe) 40 mg/kg

Summary

Introduction

Cadmium (Cd) is a nonessential transition metal without any physiological function in the human body, often considered a ubiquitous toxicant with carcinogenic activity. Alongside arsenic, lead, mercury, and chromium, poses health risks [1,2]. Human exposure to Cd occurs either in the workplace or through inhalation or ingestion of Cd-contaminated materials [3]. Occupational exposure is typical of subjects working with pigments, glass, plastics, metal alloys, and nickel-Cd batteries [4], while the main sources of exposure for the general population are cigarette smoke and foods [5]. Cd induces toxic effects in various organs, including the testes [6]. Male infertility with lower semen quality [7] and postponed puberty with reduced gonadal growth [8] were observed

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