PMID- 30228855 OWN - NLM STAT- MEDLINE DCOM- 20181116 LR - 20211204 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2018 DP - 2018 TI - Neuroprotective Effects of Polydeoxyribonucleotide in a Murine Model of Cadmium Toxicity. PG - 4285694 LID - 10.1155/2018/4285694 [doi] LID - 4285694 AB - Cadmium (Cd) is a harmful heavy metal, which causes severe brain damage and neurotoxic effects. Polydeoxyribonucleotide (PDRN) stimulates adenosine A(2A) 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), CdCl(2) (2 mg/kg/day), and CdCl(2) + 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 CdCl(2) 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 CdCl(2) 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. FAU - Marini, Herbert R AU - Marini HR AUID- ORCID: 0000-0002-8254-177X AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - Puzzolo, Domenico AU - Puzzolo D AUID- ORCID: 0000-0002-1651-1409 AD - Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy. FAU - Micali, Antonio AU - Micali A AUID- ORCID: 0000-0003-0826-1910 AD - Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy. FAU - Adamo, Elena Bianca AU - Adamo EB AD - Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy. FAU - Irrera, Natasha AU - Irrera N AUID- ORCID: 0000-0002-1134-7080 AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - Pisani, Antonina AU - Pisani A AD - Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy. FAU - Pallio, Giovanni AU - Pallio G AUID- ORCID: 0000-0002-4187-2265 AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - Trichilo, Vincenzo AU - Trichilo V AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - Malta, Consuelo AU - Malta C AD - Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy. FAU - Bitto, Alessandra AU - Bitto A AUID- ORCID: 0000-0001-9300-7532 AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - Squadrito, Francesco AU - Squadrito F AUID- ORCID: 0000-0002-8868-0762 AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - Altavilla, Domenica AU - Altavilla D AUID- ORCID: 0000-0002-1033-0527 AD - Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy. FAU - Minutoli, Letteria AU - Minutoli L AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. LA - eng PT - Journal Article DEP - 20180829 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (Polydeoxyribonucleotides) RN - 00BH33GNGH (Cadmium) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - GAN16C9B8O (Glutathione) SB - IM EIN - Oxid Med Cell Longev. 2018 Dec 13;2018:9176012. PMID: 30647819 MH - Animals MH - Brain Edema/pathology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cadmium/*toxicity MH - Disease Models, Animal MH - Glutathione/metabolism MH - Hippocampus/pathology MH - Male MH - Malondialdehyde/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neurons/drug effects/metabolism/pathology MH - Neuroprotective Agents/*pharmacology MH - Polydeoxyribonucleotides/administration & dosage/*pharmacology MH - Reaction Time/drug effects MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC6136506 EDAT- 2018/09/20 06:00 MHDA- 2018/11/18 06:00 PMCR- 2018/08/29 CRDT- 2018/09/20 06:00 PHST- 2018/04/23 00:00 [received] PHST- 2018/07/31 00:00 [accepted] PHST- 2018/09/20 06:00 [entrez] PHST- 2018/09/20 06:00 [pubmed] PHST- 2018/11/18 06:00 [medline] PHST- 2018/08/29 00:00 [pmc-release] AID - 10.1155/2018/4285694 [doi] PST - epublish SO - Oxid Med Cell Longev. 2018 Aug 29;2018:4285694. doi: 10.1155/2018/4285694. eCollection 2018.