Spirulina Ameliorates Oxidative Damage and Inflammation in Rotenone-Induced Neurotoxicity in Male Mice

Background: Rotenone, a chemical compound produced naturally by leguminous plants, has conventionally been used as a pesticide by blocking the uptake of oxygen by body cells. Our study aimed to investigate the effect of spirulina on oxidative damage, inflammation, and neurotoxicity in male mice treated by rotenone.Methods: The experimental animals were divided into 5 groups. Group (I) served as control that received Dimethyl Sulfoxide (DMSO); Group (II) mice treated with rotenone (1.5 mg/kg, s.c.3 times per week); Group (III) mice received rotenone/L-dopa (25 mg/kg, P.O. daily); Group (IV) and Group (V) mice were treated with rotenone/spirulina (200 and 400 mg/kg, P.O. daily) respectively for two weeks.Results: Rotenone-treated mice indicated impaired motor coordination and activity in wire hanging, wood walking, open field, and stair tests. Furthermore, rotenone treatment caused elevation in striatal levels of Malondialdehyde (MDA), Nitric Oxide (NO), Tumor Necrosis Factor (TNF-α), Interleukin -1 beta (IL-1β), and caspase 3 and decrement in Bcl-2; dopamine and Glutathione (GSH) levels. Moreover, severe neuronal degeneration, striatal DNA fragmentation, and increased striatal 8-OHdG levels and MTH1 expression in the rotenone group. Additionally, spirulina treatment prevented rotenone-induced motor deficits striatal DNA fragmentation and demonstrated good restoration of the substantial neurons with reservation of the typical dark appearance. Besides, rotenone-induced biochemical changes were ameliorated by spirulina treatment as dopamine, Bcl-2, and GSH levels were increased, and striatal MDA, TNF-α, IL-1β, and caspase 3 levels were decreased.Conclusion: Natural products like spirulina could reverse rotenone-induced neurotoxicity in male mice due to their anti-inflammatory and antioxidant properties

Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine

Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms and impaired memory, owing to blockade of striatal dopamine D2 receptors. Cinnarizine is a calcium channel blocker with D2 receptor blocking properties which is widely used in treatment of vertiginous disorders. The present study aimed to see whether cinnarizine would worsen the effect of haloperidol on memory function and on oxidative stress in mice brain. Cinnarizine (5, 10 or 20 mg/kg), haloperidol, or haloperidol combined with cinnarizine was administered daily via the subcutaneous route and mice were examined on weekly basis for their ability to locate a submerged plate in the water maze test. Mice were euthanized 30 days after starting drug injection. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) were determined in brain. Haloperidol substantially impaired water maze performance. The mean time taken to find the escape platform (latency) was significantly delayed by haloperidol (2 mg/kg, i.p.) on weeks 1-8 of the test, compared with saline control group. In contrast, those treated with haloperidol and cinnarizine showed significantly shorter latencies, which indicated that learning had occurred immediately. Haloperidol resulted in increased MDA in cortex, striatum, cerebellum and midbrain. GSH decreased in cortex, striatum and cerebellum and nitric oxide increased in cortex. Meanwhile, treatment with cinnarizine (20 mg/kg) and haloperidol resulted in significant decrease in MDA cortex, striatum, cerebellum and midbrain and an increase in GSH in cortex and striatum, compared with haloperidol group. These data suggest that cinnarizine improves the haloperidol induced brain oxidative stress and impairment of learning and memory in the water maze test in mice

Cannabis-induced impairment of learning and memory

Cannabis sativa preparations are the most commonly used illicit drugs worldwide. The present study aimed to investigate the effect of Cannabis sativa extract in the working memory version of the Morris water maze (MWM; Morris, 1984) test and determine the effect of standard memory enhancing drugs. Cannabis sativa was given at doses of 5, 10 or 20 mg/kg (expressed as Δ^9-tetrahydrocannabinol) alone or co-administered with donepezil (1 mg/kg), piracetam (150 mg/ kg), vinpocetine (1.5 mg/kg) or ginkgo biloba (25 mg/kg) once daily subcutaneously (s.c.) for one month. Mice were examined three times weekly for their ability to locate a submerged platform. Mice were euthanized 30 days after starting cannabis injection when biochemical assays were carried out. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, glucose and brain monoamines were determined. Cannabis resulted in a significant increase in the time taken to locate the platform and enhanced the memory impairment produced by scopolamine. This effect of cannabis decreased by memory enhancing drugs with piracetam resulting in the most-shorter latency compared with the cannabis. Biochemically, cannabis altered the oxidative status of the brain with decreased MDA, increased GSH, but decreased nitric oxide and glucose. In cannabis-treated rats, the level of GSH in brain was increased after vinpocetine and donepezil and was markedly elevated after Ginkgo biloba. Piracetam restored the decrease in glucose and nitric oxide by cannabis. Cannabis caused dose-dependent increases of brain serotonin, noradrenaline and dopamine. After cannabis treatment, noradrenaline is restored to its normal value by donepezil, vinpocetine or Ginkgo biloba, but increased by piracetam. The level of dopamine was significantly reduced by piracetam, vinpocetine or Ginkgo biloba. These data indicate that cannabis administration is associated with impaired memory performance which is likely to involve decreased brain glucose availability as well as alterations in brain monoamine neurotransmitter levels. Piracetam is more effective in ameliorating the cognitive impairments than other nootropics by alleviating the alterations in glucose, nitric oxide and dopamine in brain