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

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.

The preferential accumulation of cadmium ions among various tissues in mice

“…Biologically active compounds, such as nutraceuticals, antioxidants and anti-inflammatory agents, may provide beneficial effects and counteract Cd toxicity through targeting these molecular pathways. Some promising examples among these compounds are polyphenolic substances [ 43 , 72 , 73 ], myo-inositols [ 67 , 74 ], resveratrol [ 75 ] and flavonoids [ 76 , 77 ]. Giovanni et al reported that treatment with myo-inositol protected against Cd-induced damages in mice kidney, significantly lowered TUNEL positive cells number, and increased glutathione content and glutathione peroxidase activity in kidney.…”

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

“…The BJe used in this research was already used in our previous research [ 21 , 33 , 40 ]. Its quali-quantitative analysis showed that neohesperidin (94.00 mg/g), naringin (92.4 mg/g), melitidin (56.2 mg/g), hesperetin (51.9 mg/g), neoeriocitrin (48.6 mg/g) and naringenin (27.3 mg/g) were the most abundant flavonoids.…”

“…challenge with CdCl 2 was performed for 14 days. The doses of all substances employed were selected in accordance with previous studies [ 17 , 18 , 21 , 33 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. Twenty-four hours after the last treatment, all mice were sacrificed with an overdose of ketamine and xylazine (75/10 mg/kg i.p.…”

“…Indeed, it has been shown that BJ and its flavonoid-rich fraction (BJe) exert several biological activities, among which anti-cancer [ 21 ], anti-infective [ 22 , 23 ], hypolipemic and hypoglycemic [ 24 ], neuroprotective [ 25 , 26 ], antioxidant [ 27 , 28 ] and anti-inflammatory effects [ 29 , 30 , 31 , 32 ]. Moreover, very recently, we showed that BJe reduces the testicular damage induced by Cd through a mechanism involving its anti-inflammatory and anti-apoptotic activities [ 33 ].…”

Mediterranean Diet as a Shield against Male Infertility and Cancer Risk Induced by Environmental Pollutants: A Focus on Flavonoids

“…These authors, in fact, showed that flavonoids restored the depletion of antioxidants as they antagonized the effect of Cd on antioxidant enzyme activity or increased GSH content, improving the antioxidant capacity of the body. In parallel, a flavonoid rich-extract of bergamot juice counteracted both testicular and kidney damage induced by Cd exposure in rats [174,175]. Another research asserts that flavonoids reduced the chromosomal aberration regarding to structure and number of spermatocytes due to their detoxification action that protect protein and DNA from free radicals, and hence from cancer [173].…”