Azo food dye neurotoxicity in rats: A neurobehavioral, biochemical, and histopathological study.

Azo Food dyes (AFDs), which are widely used in the food industry, may be associated with adverse health effects. We have investigated the effects of the AFDs metanil yellow (MY), malachite green (MG), and sudan III (SIII) on cognitive impairment, oxidative stress, mitochondrial dysfunction, neuro-enzyme activities, and histopathology in rats. Rats treated with MY (430 mg/kg), MG (13.75 mg/kg), SIII (250 mg/kg), and a mixture (MY 143.33 + MG 4.52 + SIII 83.33 mg/kg) p.o. for 60 d showed significant learning and memory impairments. Significant biochemical changes were observed in the rat frontal cortex and hippocampus: increases in lipid peroxidation and the activity of acetylcholinesterase (AChE); decreases in the level of reduced glutathione and the activities of catalase, superoxide dismutase, and mitochondrial complexes I and II. Histological damage to brain neurons accompanied the learning and memory impairments and was linked with other biochemical and neurochemical alterations.

Delayed in sensorimotor reflex ontogeny, slow physical growth, and impairments in behaviour as well as dopaminergic neuronal death in mice offspring following prenatally rotenone administration.

The environment is varying day by day with the introduction of chemicals such as pesticides, most of which have not been effectively studied for their influence on a susceptible group of population involving infants and pregnant females. Rotenone is an organic pesticide used to prepare Parkinson's disease models. A lot of literature is available on the toxicity of rotenone on the adult brain, but to the best of our knowledge, effect of rotenone on prenatally exposed mice has never been investigated yet. Therefore, the recent work aims to evaluate the toxic effect of rotenone on mice, exposed prenatally. We exposed female mice to rotenone at the dose of 5 mg/Kg b.w. throughout the gestational period with oral gavage. We then investigated the effects of rotenone on neonate's central nervous systems as well as on postnatal day (PD) 35 offspring. In the rotenone group, we observed slow physical growth, delays in physical milestones and sensorimotor reflex in neonates and induction of anxiety and impairment in cognitive performances of offspring at PD-35. Additionally, immunohistochemical analysis revealed a marked reduction in TH-positive neurons in substantia nigra. Histological examination of the cerebellum revealed a decrease in Purkinje neurons in the rotenone exposed group as compared to the control. The data from the study showed that prenatally exposure to rotenone affects growth, physical milestones, neuronal population and behaviour of mice when indirectly exposed to the offspring through their mother. This study could provide a great contribution to researchers to find out the molecular mechanism and participating signalling pathway behind these outcomes.

Neuroprotective effect of quercetin against rotenone-induced neuroinflammation and alterations in mice behavior.

Various studies suggested that neuroinflammation leads to the development of several neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). Rotenone is an organic pesticide and potent inhibitor of complex I of electron transport chain widely used to develop the PD model. Numerous studies reported rotenone toxicity in the dopaminergic system but very few studies are available on rotenone-induced glial cell activation and subsequent neurodegeneration and alterations in various types of behavior. Therefore, the present study was designed to explore the effect of rotenone on neuroinflammation and its deleterious effect on the behavior of mice, and also how these effects can be protected through quercetin. Quercetin, a natural flavonoid having strong antioxidant and anti-inflammatory properties, is found in vegetables and fruits. The finding of the study indicated that rotenone 5 mg/kg body weight for 60 days through oral gavage leads to the release of inflammatory markers in blood serum, astrocytes activation in substantia nigra and hippocampus, and subsequently decreased density of dopaminergic fibers in the striatum. Rotenone also altered the memory of the mice as indicated by decreased spontaneous alteration in Y-maze and T-maze tests and reduction in exploration time in novel object recognition, increased immobility time in the forced swim test and reduced muscular strength. Co-treatment of quercetin 30 mg/kg/day through oral gavage for 60 days along with rotenone significantly reversed all these adverse effects, suggesting that quercetin could reduce neuroinflammation, and improve memory, and cognitive function.

Non-permitted food colorants induced neurotoxicity in cerebellum of rat brain.

Food colorants are important food additives that not only enhance the appearance of food but also appetite. These can be obtained from natural and synthetic sources, but synthetic sources are more popular, efficient, and potential. Non-permitted food colorants (NPFCs) are banned, but their injudicious use in developing countries associated with various adverse health effects. They have potentially toxic effects on the body organs like the brain, liver, kidney, spleen, gut, etc. In view of their toxicity pattern, the present study aims to investigate the effect of three NPFCs (MY: Metanil yellow; MG: Malachite green; SIII: Sudan III) on oxidative stress, mitochondrial complexes, neurochemicals, and histological changes in the cerebellum of rats. Rats treated with MY (430 mg/kg), MG (13.75 mg/kg), SIII (250 mg/kg), and their mixtures (YGR) (MY 143.33 + MG 4.52 + SIII 83.33 mg/kg) p.o. for 60 days showed a significant increase in lipid peroxidation and decreased level of reduced glutathione, superoxide dismutase, and catalase activity as compared to controls. An increase in the activity of acetylcholinesterase (AChE) and a significant decrease in the activity of monoamine oxidase-B (MAO-B) and mitochondrial complex I and II was also observed in NPFCs treated rats as compared to controls. Further, the histological study also revealed the loss of Purkinje neurons in the cerebellum of the rat brain. The results of the present study indicate that NPFCs exposure to rats enhances oxidative stress and alters the activity of neurochemicals and mitochondrial complexes which could further lead to neuronal loss and behavioral dysfunctions.

Neuroprotective effects of mitochondria-targeted curcumin against rotenone-induced oxidative damage in cerebellum of mice.

The present study investigated the protective effect of curcumin and mitochondrial-targeted curcumin (MTC) in rotenone-induced cerebellar toxicity in mice. Treatment of rotenone in mice significantly shortened the stride length for both forelimb and hind-limb and increased fore-paws and hind-limb base width. Co-treatment of curcumin and MTC with rotenone improved the walking pattern. A significant increase in lipid peroxidation, nitric oxide and decreased activity of AChE, reduced glutathione, superoxide dismutase and catalase were observed in rotenone-treated mice while co-treatment of curcumin and MTC with rotenone significantly increased AChE activity and protected against rotenone-induced oxidative damage. Rotenone exposed mice showed irregular, damaged Purkinje cells and perineuronal vacuolation while co-treatment of curcumin and MTC with rotenone protected against rotenone-induced cellular damage in these cells. The result exhibits that both curcumin and MTC showed protective effects against rotenone-induced cerebellar toxicity in mice and MTC is more effective than curcumin.