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

Abstract

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.

Decreased thioredoxin reductase 3 expression promotes nickel‐induced damage to cardiac tissue via activating oxidative stress‐induced apoptosis and inflammation

“…46 Txnrd2 deletion leads to an increase in infarction size and apoptosis of cardiomyocytes and impairs postischemic functional recovery of the heart. 47 48,49 We performed the median lethal dose (LD 50 ) and concentration gradient pre-experiments (the concentrations of NiCl 2 solution were set at 8, 10, and 12 mg/kg; the concentrations of Mel solution were set at 2, 5, and 8 mg/kg) to determine the lowest concentration of NiCl 2 that could cause damage in mice and the maximum concentration of Mel that could treat for Ni without causing damage. All animals had free access to food and water for 21 days, and mice were then placed in clean containers and euthanized by slow infusion of carbon dioxide (CO 2 ).…”

Mechanistic considerations and biomarkers level in nickel-induced neurodegenerative diseases: An updated systematic review

“… Ijomone et al (2018b) 8 Impact of exposure to waterborne NiCl 2 concentrations (75 and 150 μg/L).on neurobehavioral performances of rats Rat brain Adverse motor activities; negative geotaxis, grooming, grip strength and body rotation Significant elevation in RONS, LPO, MPO, NO, IL-1β and TNF-α levels in cerebrum and cerebellum of treated rats Adedara et al (2020) 9 Effects of Ni exposure through drinking water (10 mg/L, 12 weeks) on neurobehavioral performances and dendrite complexity Male mice Learning and memory impairment in mice, and reduction of dendrite complexity in mouse hippocampi Reduction of histone acetylation (especially at H3K9) and downregulation of H3K9-modulated gene expression Zhou et al (2021) 10 Nickel-induced neurobehavioral alterations in male and female rats after NiCl 2 treatment (1 mg/kg for 60 days) Male and female rats Increased anxiety-like and depression-like behaviour in rats. Cognitive behaviour on the Morris water maze resulted compromised LPO and NO formation with a decrease in SOD and CAT activities Lamtai et al (2020) 11 Neuroprotective potential of melatonin on Ni-induced neurobehavioral alterations in male and female rats C. elegans Functional changes in locomotion and basal slowing response Increasing degeneration of cholinergic, dopaminergic and GABAergic neurons Ijomone et al (2020b) 12 Effects of Ni 2+ on neurotoxic outcomes PC12 cells Changes in oxidative-stress-related gene expression Downregulation of GST Slotkin and Seidler (2010) 13 Effects of nickel concentration (10 μM) on the expression of specific neuronal differentiation markers NT2 cells Nickel may increase the susceptibility to neuro-psychopathology Activation of Akt/PKB kinase pathway and increase of HIF-1a expression. Increased expression of differentiation markers MAP2 and NCAM Ceci et al (2015) 14 Activity of HO measured in tissues of rats after NiCl 2 administration Rat tissue HO activity increased in liver, lung and brain at 17 hr after the NiCl 2 injection Time course, dose-effect, organ selectivity, and species susceptibility relationships for Ni induction of HO activity …”

“…These findings were comparable to previous reports on the association of Ni exposure with memory retention and increased the escape latency using the Morris water maze (MWM) ( Kahloula et al, 2014 , He et.al, 2013 ). Specifically, nickel increases the hippocampal level of thiobarbituric acid reactive substances (TBARS) (markers of LPO), and decrease SOD and CAT activities which may culminate in increased anxiety-like and depression-like behaviour in rats ( Lamtai et al, 2020 ). This last study performed histopathological analyses of CA3 pyramidal neurons observing neuronal loss, cellular disorganization, and shrinkage in nickel treated rats of both genders compared to their normal controls ( Lamtai et al, 2020 , El Brouzi et al, 2021 ) demonstrated that intracerebral injection of NiCl 2 at the right hippocampus of the male Wistar rat causes anxiety and depression disorders and lead to cognitive impairment, and again the mechanism was the increase in LPO and NO levels accompanied by a significant decrease in SOD and CAT activities in the hippocampus.…”

“…In addition, Ni 2+ exposure can inhibit and stimulate release of dopamine and also inhibit glutamate NMDA (N-methyl- D -aspartate) receptors ( Martínez-Martínez et al, 2020 ). Therefore, molecules that constrain the oxidative stress potentially protect neuronal cells and subsequently prevent neurobehavioral disturbances, as demonstrated by melatonin administered to rats exposed to the metal ( Lamtai et al, 2020 , Rao et al, 2009 ) pointed out that the supplementation of vitamin E with nickel and chromium to mice exhibited protective effect in the ovary.…”

“…2008 , Wu et al, 2016 ). Nickel was implicated in cognitive and behavioural deficits in rats with elevated levels of exposure to the metal ( Lamtai et.al., 2020 ). Nickel can result in distinct neurological effects, with different brain targets and modes of action, and it can disrupt presynaptic neurotransmission.…”