Ameliorative Effect of Palm Oil in Aluminum Lactate Induced Biochemical and Histological Implications in Rat Brain.

α-Tocotrienol is one of the major constituents of palm oil. It is a well-known antioxidant and cholesterol-lowering neuroprotectant. To prevent the initiation of Alzheimer's like symptoms, much attention has been shifted to the major role played by antioxidants. Previous epidemiological reports correlate the increasing incidence of developing Alzheimer's disease (AD), to the aluminum (Al) content in drinking water. Al, being a ubiquitous element, has a long history of being particularly reactive towards multiple aspects of neurobiology. So, the current study examines the effect of Al-induced behavioral, biochemical, and histopathological changes in rat brain; and the ameliorative effect of palm oil in reducing the resulting neurotoxicity. The experimental design consisted of 4 groups: control group which received rodent chow diet and water ad libitum; Al group received aluminum lactate (50 mg/kg bw); Al + palm oil group was administered with Al (50 mg/kg bw) and palm oil (60 mg/kg bw); and palm oil group received palm oil (60 mg/kg bw). Al was given by oral gavage once daily for 6 weeks and palm oil was administered intraperitoneally. After 6 weeks of supplementation, Al + palm oil group showed significantly lower malondialdehyde (MDA) content, but higher superoxide dismutase (SOD), catalase (CAT), GST, and GPx activity as compared to Al group. Al group has significantly higher level of MDA content, but lower SOD, CAT, GST, and GPx activity as compared to control group. In conclusion, this study suggested that palm oil was effective in preventing the Al-induced brain damage in rats.

Neuroprotective Role of Lazaroids Against Aluminium Chloride Poisoning.

Aluminium (Al) is neurotoxic primarily because of its interference with biological enzymes in key mechanisms of metabolic pathways. Mitochondria being a major site of reactive oxygen species (ROS) production, it seems that the oxidative damage to mitochondrial proteins may underlie the pathogenesis of Al induced neurodegeneration. The present study investigates the effectiveness of the anti-oxidant property of lazaroids (U-74500A), a known lipid peroxidation inhibitor as neuroprotective agent against Al induced neurotoxicity. Al chloride was administered orally at a dose level of 100 mg/kg body wt/day in water and U-74500A was administered at a dose of 0.25 mg/kg body wt i.p. in citrate buffer for a period of 8 weeks on alternate days. Following Al exposure there was a significant increase in lipid peroxidation (LPO), ROS levels and reduction in the activity of mitochondrial complexes in all the three regions of rat brain, i.e., cerebral cortex, mid brain, and cerebellum. This decrease in the activities of electron transport complexes in turn affected the ATP synthesis and ATP levels adversely in the mitochondria. These alterations were also depicted in the histology which shows signs of hypoxia, paucity of neurons in cortical region and loosening of fibers in the white matter. U-74500A co-administration was able to restore alterations in the LPO, ROS levels as well as all the three mitochondrial complexes and caspase expression. Therefore, it is suggested that 21-aminosteroids (lazaroids), by attenuating LPO and mitochondrial dysfunction, holds a promise as an agent that can potentially reduce Al-induced adverse effects in brain.

Consequences of nicotine exposure during different phases of rat brain development.

Nicotine is a psychoactive drug whose intensity of the addiction is so tremendous that it is now the fastest growing public health hazard in the world. The present study was designed to study the toxic effects of nicotine during different phases of rat brain development. The study is extended through adult brain designated as group A, that received nicotine at the dosage of 5 mg/kg of b.wt. for 21 days and were sacrificed following 21 days of recovery. In the second group P, pups in different gestational phases (P2-P4) were given maternal nicotine exposures for only a period of 7 days followed by recovery till they had achieved the age of 40 days. A significant decrease in long term memory was observed in adult rats which correlated well with a significant decrease in the acetylcholine esterase activity. Simultaneously a significant decrease in the total glutathione, GSH content and catalase activity was observed which could account for the increase in peroxidation of lipids as evaluated by malondialdehyde (MDA) content in the nicotine exposed adult rats. The consequences of maternal nicotine exposure were different during different exposures regimes the alterations were least during the early gestation period, i.e. P2 (2-9 days of their gestation period) as compared to P3 (7-14 days of their gestation period) and P4 (21 days of their weanling period). The study indicates that the consequences of nicotine exposure are varied during different stages of brain development.

Stress proteins and glial cell functions during chronic aluminium exposures: protective role of curcumin.

Involved in the ongoing debate is the speculation that aluminium is somehow toxic for neurons. Glial cells cope up to protect neurons from this toxic insult by maintaining the glutathione homeostasis. Of late newer and newer roles of glial cells have been depicted. The present work looks into the other regulatory mechanisms that show the glial cells response to pro-oxidant effects of aluminium exposure. In the present investigation we have evaluated the inflammatory responses of the glial cells as well as HSP70-induction during aluminium exposure. Further, the protective role of curcumin is also evaluated. Aluminium was administered by oral gavage at a dose level of 100 mg/kg b.wt/day for a period of 8 weeks. Curcumin was administered i.p. at a dose of 50 mg/kg b.wt./day on alternate days. Enhanced gene and protein expression of HSP70 in the glial fractions of the aluminium exposed animals as compared to the corresponding neuronal population. Aluminium exposure resulted in a significant increase in the NF-κB and TNF-α expression suggesting inflammatory responses. In the conjunctive treatment group of aluminium and curcumin exposure marked reduction in the gene and protein expression of NF-κB and TNF-α was observed. This was further reflected in histopathological studies showing no evidence of inflammation in conjunctive group as compared to aluminium treatment. From the present study, it can be concluded that curcumin has a potential anti-inflammatory action and can be exploited in other toxicological conditions also.

Curcumin attenuates aluminum-induced oxidative stress and mitochondrial dysfunction in rat brain.

Aluminum is neurotoxic both in animals and human beings primarily because of its interference with biological enzymes in key mechanisms of metabolic pathways. Mitochondrial dysfunction is one such mechanism that has been implicated in the pathogenesis of neurodegenerative diseases like Alzheimer's disease. Aluminum toxicity is very closely related to Alzheimer's disease. We evaluated the potentials of curcumin, a known cytoprotectant, against neurotoxic consequences of aluminum that acts through a wide range of mechanisms. Curcumin has been reported to be an antioxidant, and it is this property that is widely held to be responsible for its protective effects in tissue. Aluminum was administered by oral gavage at a dose level of 100 mg/kg body wt/day for a period of 8 weeks. Curcumin was administered in conjunction with aluminum at a dose of 50 mg/kg of body wt i.p. for a period of 8 weeks on alternate days. The effects of different treatments were studied on oxidative phosphorylation and reduced glutathione of different regions of rat brain. The study indicates reduced activity of NADH dehydrogenase (complex I), succinic dehydrogenase (complex II), and cytochrome oxidize (Complex IV) in all the three regions of rat brain, i.e., cerebral cortex, mid brain, and cerebellum. Curcumin supplementation to aluminum-treated rats was able to normalize significantly the activities of all the three mitochondrial complexes as well as reduced glutathione content in all the three regions of brain which were altered following aluminum treatment. We conclude that curcumin, by attenuating oxidative stress, as evident by hypoxia in histological observations and mitochondrial dysfunction holds a promise as an agent that can potentially reduce aluminum-induced adverse effects in brain.

Beneficial effects of folic acid on enhancement of memory and antioxidant status in aged rat brain.

As our population ages, diseases affecting memory and daily functioning will affect an increasing number of individuals, their families and the healthcare system. Therefore, there is a need to study and evaluate effects of certain conditions for anti-aging of the brain. Nutrient supplementation can modify the brain function. The chemistry and function of both the developing and the mature brain are influenced by diet (Fernstrom, Am J Clinical Nutrition 71:1669S-1673S, 2000). Clinical, biochemical, and pathological aspects have shown a correlation between mental symptoms, especially depression and cognitive decline, with high incidence of folate deficiency (Bottiglieri et al., J Neurol Neurosurg Psychiatry 69:562, 2000). In the present study, consequences of folic acid supplementation on brain dysfunction as a result of aging were studied in cerebral cortex, mid brain, and cerebellar regions of rat brain. This study was carried out on 6-, 11-, and 16-month-old rats, which received folic acid at a dose of 5 mg/kg body weight/day for a period of 8 weeks. Respective control groups of the same age groups were also taken. At the end of the treatment duration, behavioral studies were performed and later the animals were killed for various biochemical and histological investigations. Results indicated significant improvement in memory as assessed by active avoidance, passive avoidance, and plus maze tests in the folic acid supplemented aged animals. Significant improvement was also seen in the cellular protective mechanisms where by the activity of superoxide dismutase and catalase enzymes increased in folic acid supplemented group and so was the glutathione content. Increased lipid peroxidation content, a marker of aging, was also found to be decreased during folic acid supplementation in all the three regions of brain in our study. Thus, it can be concluded that folic acid helps in improving the memory status by reducing oxidative stress and maintaining the integrity of neurons during aging.

PD168077, a D(4) receptor agonist, reverses object recognition deficits in rats: potential role for D(4) receptor mechanisms in improving cognitive dysfunction in schizophrenia.

This study investigated the effects of the dopamine D(4) receptor agonist, PD168077, on recognition memory using a novel object recognition task, which detects disruption and improvement of recognition memory in rats by measuring their ability to discriminate between familiar and novel objects. When acquisition and test were 6 h apart (experiment 1), control rats failed to discriminate between familiar and novel objects at test. Rats given low doses of PD168077 (0.3; 1.0 mg/kg) also failed to discriminate between the objects, while rats given higher doses (3.0; 10.0 mg/kg) explored the novel object more than the familiar object, indicating retained memory of the familiar object. Thus, at higher doses, PD168077 improved recognition memory in rats. Experiment 2 tested whether PD168077 would attenuate deficits in novel object recognition induced by sub-chronic phencyclidine. Testing was 1 min after acquisition, such that vehicle pre-treated rats differentiated between the novel and familiar objects: however, sub-chronic phencyclidine-treated rats failed to discriminate between the two, indicating disruption of recognition memory. PD168077 (10 mg/kg) restored the ability of phencyclidine-treated rats to differentiate between the novel and familiar objects, indicating improved recognition memory. The results suggest that D(4) receptor activation can improve cognitive dysfunction in an animal model relevant to schizophrenia.

Evaluation of metaquant microdialysis for measurement of absolute concentrations of amphetamine and dopamine in brain: a viable method for assessing pharmacokinetic profile of drugs in the brain.

Direct measurement of absolute brain concentration of amphetamine and dopamine were obtained using metaquant (MQ) microdialysis, which achieves near 100% recovery, in the caudate nucleus. Conventional microdialysis monoprobes were also implanted in the caudate nucleus in the contralateral side of the same animals to compare the brain concentrations obtained from these two probe types. In addition plasma concentrations of amphetamine were obtained simultaneously from the same animals. The distribution of amphetamine in the plasma and of amphetamine and dopamine in both probe types followed same profile at each time interval. The basal dialysate concentration of dopamine in the caudate nucleus measured by MQ, was 9.40+/-0.60 nM, while measured by conventional microdialysis it was 6.35+/-0.36 nM. This study demonstrates that MQ microdialysis is an appropriate method for determination of true extracellular levels of drugs and neurotransmitters in the brain, under dynamic conditions. Since these measurements, together with measurements of plasma concentrations of the drug, can be made in a single animal, the method can be used to study pharmacokinetic-pharmacodyamics profile of psychoactive agents.