Abstract
Cadmium (Cd) is a harmful heavy metal, which causes severe brain damage and neurotoxic effects. Polydeoxyribonucleotide (PDRN) stimulates adenosine A2A receptor, thus contrasting several deleterious mechanisms in course of tissue damages. We aimed to investigate the possible neuroprotective effect of PDRN in a murine model of Cd-induced brain toxicity. Male C57 BL/6J mice were treated as follows: vehicle (0.9% NaCl, 1 ml/kg/day), PDRN (8 mg/kg/day), CdCl2 (2 mg/kg/day), and CdCl2 + PDRN. Animals were tested with the Morris water maze test to assess spatial memory and learning. After 14 days of treatment, brains were processed to evaluate the presence of edema in the cerebral tissue, the expression of mammalian target of rapamycin kinase (mTOR) and brain-derived neurotrophic factor (BDNF), and the morphological behavior of the hippocampal structures. After CdCl2 administration, the escape latency was high, protein expression of BDNF was significantly decreased if compared to controls, mTOR levels were higher than normal controls, and brain edema and neuronal damages were evident. The coadministration of CdCl2 and PDRN significantly diminished the escape latency, increased BDNF levels, and decreased protein expression of mTOR. Furthermore, brain edema was reduced and the structural organization and the number of neurons, particularly in the CA1 and CA3 hippocampal areas, were improved. In conclusion, a functional, biochemical, and morphological protective effect of PDRN against Cd induced toxicity was demonstrated in mouse brain.
Highlights
Cadmium (Cd) is an extremely toxic metal with no known necessary function in the human body
Fifty-six male adult C57 BL/6J mice (25–30 g), obtained from Charles River Laboratories Italia srl (Calco, Italy), were provided a standard diet ad libitum with free access to tap water under a 12 h light/dark cycle. They were divided into four groups: (i) animals administered with a vehicle solution consisting in 0.9% NaCl (1 ml/kg, ip, daily), indicated as “control + vehicle animals,” (ii) animals administered with PDRN (8 mg/kg, ip daily), indicated as “control + PDRN animals,” (iii) animals challenged with CdCl2 plus with the vehicle as above (2 mg/kg, ip, daily), indicated as “CdCl2 + vehicle animals,” and (iv) animals challenged with CdCl2 (2 mg/kg, ip, daily) and treated with PDRN (8 mg/kg, ip, daily), immediately following CdCl2 administration, indicated as “CdCl2 + PDRN animals.”
Oxidative stress is strongly related to neuroinflammatory mechanisms, so that it is difficult to exert neuroprotective effects on the brain
Summary
Cadmium (Cd) is an extremely toxic metal with no known necessary function in the human body. Major sources of Cd are food, cigarette smoke, and recharged nickel-cadmium batteries [2]. Vegetables, nuts and pulses, starchy roots, potatoes, and meat products are the main source of Cd exposure for the nonsmoking population [3]. Several reports studied Cd toxicity in the brain as a whole or in its specific regions. Cd can experimentally induce neurotoxic effects either in vitro or in vivo. Neurotoxic effects were described in neonatal mouse [9] and in adult rat brain [10] and in diabetic rat optic nerve experimentally exposed to Cd [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
