Potential Role of Oxidative Stress in the Effects of Chronic Administration of Iron on Affective and Cognitive Behavior on Male Wistar Rat.

In this work, we studied the impact of chronic iron exposure, in the form of iron sulfate (FeSo4), on affective and cognitive disorders and oxidative stress in the male Wistar rat. The treatment was carried out for 8 weeks, the rats received an intraperitoneal injection of iron at different doses: 0.25, 0.5, and 1 mg/kg. Affective and cognitive disorders are assessed in open field test (OFT), elevated plus maze (EPM), forced swimming test (FST), Morris water maze (MWM), and Y-maze. The hippocampus and prefrontal cortex of each animal were taken for biochemical examination. Our results show that iron exerts anxiogenic and depressogenic effects, which were observed first at the dose of 0.5 mg/kg and continued in a dose-dependent manner up to the maximum tested dose of 1 mg/kg. According to results from the MWM and Y-maze tests, continuous exposure to iron induces cognitive disorders that are defined by the disturbance of working memory and influences spatial learning performance causing a deficit of spatial memory retention. We noted that chronic exposure to iron can be associated with the appearance of a state of oxidative stress in the hippocampus and the prefrontal cortex demonstrated by an increase in lipid peroxidation, an increase in nitric oxide, and also by disturbances in the antioxidant defense systems following a determination of the concentrations of catalase. In conclusion, we can deduce from this work that chronic iron exposure can be related to the induction of cognitive and affective disorders and oxidative stress.

Neuroprotective effect of melatonin on nickel-induced affective and cognitive disorders and oxidative damage in rats.

The present work is carried out to explore the neuroprotective potential of Melatonin(Mel), on Ni-induced neurobehavioral, biochemical and histological alterations in male and female rats. The rats were intraperitoneally administered by nickel chloride (NiCl2, 1 mg/kg) and Mel (4 mg/kg) for 60 days. A neurobehavioral assessment was performed. Biochemical determinations of oxidative stress (OS) levels, and histological analysis of hippocampal tissues were also performed. Results showed that Nickel (Ni) treatment increased anxiety-like and depression-like behavior in rats. Besides, cognitive behavior on the Morris water maze was compromised following Ni treatment. Alongside this, Ni elevated hippocampal OS markers like lipid peroxidation and nitric oxide formation with a decrease in superoxide dismutase and catalase activities. Histological observations confirmed these results. Significantly, Mel administration alleviated neurobehavioral changes in Ni-treated rats of both genders. Also, Mel attenuated Ni-induced OS and increased the activities of antioxidant enzymes. The histopathological studies in the hippocampus supported that Mel markedly reduced the Ni-induced neuronal loss. In conclusion, this study suggests that Mel has a neuroprotective effect against Ni-induced neurobehavioral alterations, which may be related to lowering OS in the hippocampus.

Anticonvulsant effect of argan oil on pilocarpine model induced status epilepticus in wistar rats.

Argan oil (AO) is rich in oleic and linoleic acids, polyphenols, sterols, and tocopherols. This composition gives it numerous beneficial pharmacological effects such as hypolipemiant, hypotensive, and antiproliferative. Oxidative stress is a mechanism of cell death induced by seizures and status epilepticus (SE). This study aims at investigating AO effects on (i) latency to first seizure, seizure severity, weight loss, mortality rate, (ii) lipid peroxidation level, nitrite level, and catalase activity in the hippocampus after SE induced by pilocarpine (PC). Wistar rats (1-month old) were daily administered by oral gavage with AO (1 ml/100 g/day) or with NaCl 0.9% during 2 months before receiving PC (400 mg/kg). After the PC injection, all groups were observed for 24 h. The catalase activity, the lipid peroxidation, and nitrite concentrations were measured using spectrophotometric methods. AO pretreatment increased the latency to first seizures, decreased the weight loss, and reduced mortality rate after SE. AO pretreatment produces significant decrease of the lipid peroxidation and nitrite levels. On the contrary, AO increased the catalase activity in rat hippocampus after seizures. For the first time, our results suggest that AO pretreatment is capable of attenuating seizure severity and oxidative stress in the hippocampus of Wistar rats. This indicates that AO may exhibit a neuroprotection against the temporal lobe epilepsy. Further investigations are in progress to confirm this pharmacological property.

SLC11A1 polymorphisms and susceptibility to visceral leishmaniasis in Moroccan patients.

Human visceral leishmaniasis is endemic in the Mediterranean basin. Since most infections are sub-clinical or asymptomatic, host genetics can provide concrete evidence in determining disease outcome. SLC11A1/NRAMP1 is a candidate gene that may be related to host susceptibility versus resistance to intracellular pathogens. This study aimed to determine possible association of SLC11A1 polymorphisms with visceral leishmaniasis among Moroccan children. A total of 106 children who developed visceral leishmaniasis due to Leishmania infantum were enrolled in this study. The control group was composed of 137 unrelated children, 97 asymptomatic subjects (DTH+) and 42 healthy individuals (DTH) who had no evidence of present or past infection. Four polymorphisms were studied by PCR-RFLP and sequencing: (GT)n microsatellite in the 5' exon 1; silent substitutions 469+14G/C in intron 4; amino acid substitution D543N in exon 15 and 823C/T polymorphism in exon 8. Thereafter, the frequencies of genotypes, alleles and haplotypes were estimated. Two polymorphisms were each significantly associated in the genotypes with visceral leishmaniasis: 823C/T in exon 8 and D543N in exon 15 when comparing visceral leishmaniasis and DTH+ groups. The results of haplotype frequencies suggested an evidence of association with resistance to visceral leishmaniasis for the "286GTG" and "288GCA" haplotypes, whereas, the "286GCG" haplotype appears to increase the risk to visceral leishmaniasis susceptibility.Our data provide insights into the possible role of SLC11A1 variation in visceral leishmaniasis susceptibility. These results must be regarded as preliminary but suggestive that further study with larger populations is worthwhile.