Manganese neurotoxicity and protective effects of resveratrol and quercetin in preclinical research.
BACKGROUND
Exposure to Mn results in a neurological syndrome known as manganism.


METHODS
We examined how 4-week Mn exposure (20mg/kg MnCl2po, 5days/week) induces neurotoxic effects in rats. Oxidized-to-reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, catalase (CAT) activity, vitamin E content and caspase-3 activity were measured in several rat brain structures. Further, we examined protective effects of the polyphenols: resveratrol (R) or quercetin (QCT) against Mn-induced neurotoxicity.


RESULTS
After exposure to Mn, we found a rise in GSSG/GSH ratio and a reduction in SOD activity in the rat striatum (STR), while in the nucleus accumbens (NAC) decreases in alpha-tocopherol content and in SOD activity were noted. In the frontal cortex (FCX), an enhancement in GSSG/GSH ratio and a reduction in SOD and CAT activities were observed. In the cerebellum (CER), a significant increase in the caspase-3 activity paralleled a rise in the GSSG/GSH ratio and a diminution of SOD activity. In the rat hippocampus (HIP), Mn evoked an enhancement in GSSG/GSH ratio. There were no changes in the MDA levels. Pretreatment with R and QCT protected against the Mn-induced (i) enhancement in GSSG/GSH ratio in the STR, (ii) decreases in the NAC alpha-tocopherol content and (iii) reduction in SOD activity in FCX, NAC and CER.


CONCLUSIONS
Repeated Mn administration induces toxic effects in several rat brain structures and treatment with R and QCT may be a potential therapeutic strategy to attenuate the metal neurotoxicity.
Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland. Electronic address: mfgawlik@cyf-kr.edu.pl.
Maciej
M
Gawlik
Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Małgorzata B
MB
Gawlik
Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Irena
I
Smaga
Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Drug Addiction Pharmacology, Kraków, Poland.
Małgorzata
M
Filip
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008345:Manganese / Q000009:adverse effects*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism; D024502:alpha-Tocopherol / Q000378:metabolism
D020011:Protective Agents; D013267:Stilbenes; D014810:Vitamin E; D008345:Manganese; D008315:Malondialdehyde; D011794:Quercetin; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione; D024502:alpha-Tocopherol; D000077185:Resveratrol
Manganese; Neuroprotection; Quercetin; Rat brain; Resveratrol