Cardioprotective effects of insulin on carbon monoxide-induced toxicity in male rats.

Carbon monoxide (CO) poisoning is a significant cause of death especially in developing countries. The current study investigated cardioprotective effects of insulin in CO-poisoned rats. Male rats were exposed to 3000 ppm CO for 1 h. Insulin (100 and 120 U/kg intraperitoneally) was immediately administered after CO exposure and on the next 4 days, on a daily basis (a total of 5 doses). On day 5, animals were euthanized, and the hearts were harvested for Western blotting and histopathological studies. The electrocardiograms (ECG) were recorded postexposure to CO and after the completion of insulin treatment period. Histopathological evaluations showed reduction of myocardial necrosis in insulin-treated animals compared to controls. BAX/BCL2 ratio, as a proapoptotic index, was significantly reduced in treatment groups ( p < 0.01). The ECG findings showed no differences among groups; also, compared to control animals, myocardial Akt levels were not markedly affected by insulin. The current study showed that insulin significantly reduces myocardial necrotic and apoptotic indices in CO-poisoned rats.

Behavioral and molecular effects of intrahippocampal infusion of auraptene, resveratrol, and curcumin on H-89-induced deficits on spatial memory acquisition and retention in Morris water maze.

Our aim was to investigate the effects of resveratrol, auraptene, and curcumin on the spatial learning and spatial memory retention in the Morris water maze (MWM). The effects of 4-day bilateral intrahippocampal (i.h.) infusions of dimethyl sulfoxide (DMSO), H-89 as a protein kinase AII inhibitor, auraptene/H-89, resveratrol/H-89, and curcumin/H-89 were investigated on spatial memory acquisition in MWM. The rats were trained for 4 days; each day included one block of four trials. Post-training probe tests were performed on day 5 in acquisition test. For retention assessments, different animals were trained for 4 days and then infused (i.h.) with either DMSO, H-89, auraptene/H-89, resveratrol/H-89, or curcumin/H-89. The retention test was performed 48 h after the last training trial. The bilateral infusion of H-89 led to a significant impairment in spatial memory in acquisition and retention tests accompanied with a significant decrease in expressions of cAMP response-element binding (CREB) and pCREB proteins in hippocampus. Resveratrol and curcumin reversed the H-89-induced spatial memory acquisition and retention impairments with significant increases in both CREB and pCREB proteins expressions compared to H-89-treated animals. Auraptene showed significant effects in reversing H-89-induced impairments in spatial memory retention but not spatial memory acquisition.

Mechanistic approach for the toxic effects of perfluorooctanoic acid on isolated rat liver and brain mitochondria.

BACKGROUND: Perfluorooctanoic acid (PFOA) is one of the most widely used perfluoroalkanes as surfactants, lubricants and processing aids in the production of polymers, which has also been detected in the environment, wildlife and human body. Animal studies indicated that PFOA caused a wide array of toxic effects including liver and brain dysfunction, carcinogenicity and reproductive and developmental toxicity. Based on the established role of mitochondria-mediated pathways in the observed toxic effects of many drugs and chemicals, in this study, the potential toxic effects of PFOA on mitochondria isolated from rat liver and brain have been investigated. METHOD: Mitochondria were isolated by differential centrifugation method and incubated with different concentrations of PFOA (0.5-1.5 mM). The effects of PFOA were assessed on a series of mitochondrial parameters including reactive oxygen species (ROS) formation, activities of mitochondrial complexes I/II/III, reduced glutathione (GSH) content, adenosine triphosphate (ATP) level, membrane potential, lipid peroxidation (LPO), mitochondrial swelling and cytochrome c release. RESULTS: The data on liver mitochondria indicated that PFOA-induced ROS elevation in both mitochondrial complexes I and III, mitochondrial membrane potential collapse, swelling, cytochrome c release and decreased ATP level which induces apoptosis or necrosis. On brain mitochondria, PFOA showed fairly similar effects on the above-mentioned parameters. However, different results were obtained when the effect of PFOA was assessed on LPO and complex II activity. CONCLUSIONS: Due to the fact that PFOA had toxic effects on the mitochondria isolated, it could be suggested that mitochondrial toxicity could be a plausible mechanism for the toxic effects of this fluorochemical on liver and brain function.

Anti-inflammatory and anti-nociceptive effects of the ethanolic extracts of Alkanna frigida and Alkanna orientalis.

Alkanna species are used in Iranian traditional medicine for treatment of rheumatoid arthritis and other inflammatory diseases. This study was designed to evaluate the anti-inflammatory and anti-nociceptive effects of Alkanna frigida and Alkanna orientalis ethanolic extracts via the carrageenan-induced paw edema test and formalin test in rat and mouse, respectively. Ethanolic extracts of plant root were prepared and were injected intraperitoneally 60 min before carrageenan-induced inflammation or formalin-induced nociception at 100, 200 and 400 mg/kg. Anti-inflammatory effects of plants were monitored for 3 h after carrageenan injection and anti-nociceptive effects were evaluated during the first hour after formalin injection. Diclofenac, a well-known anti-inflammatory and anti-nociceptive agent, was used as a positive control. Our results show that, in contrast to Alkanna orientalis, ethanolic extract of Alkanna frigida significantly decreases carrageenan-induced inflammation at 400 mg/kg, especially 3 h after inflammation induction. Both Alkanna frigida and Alkanna orientalis ethanolic extracts possess a remarkable anti-nociceptive effect at each dose (100, 200 and 400 mg/kg) in a dose-dependent manner during the first hour after formalin injection.The present findings provide more evidence for the potential anti-nociceptive effect of Alkanna sp. and the anti-inflammatory effect of Alkanna frigida. It supports their traditional indication in the treatment of pain and inflammatory-related diseases. These useful effects may result from the inhibitory interaction of the plant ethanolic extract with cyclooxygenase-2 enzyme and the subsequent reduction in prostaglandin production.

Effects of training in the Morris water maze on the spatial learning acquisition and VAChT expression in male rats.

BACKGROUND AND THE PURPOSE OF THE STUDY: It has been well established that cholinergic pathway plays an important role in learning and memory processes. The present study was designed to evaluate the effects of Morris water maze (MWM) training on spatial memory acquisition and expression of the vesicular acetylcholine transporter (VAChT) in male rats. METHODS: In this study, training trials of all groups of animals were conducted in the MWM task. Rats received one training session consisting of four trials per day which continued for another four consecutive days. Controls received visible platform MWM training. The escape latency, the traveled distance and swimming speed for each rat were recorded and used to evaluate the performance of the animal during training period. For evaluation of expression of VAChT protein levels, brain tissues from animals in each experiment were obtained immediately after the last trial on the related experimental day and processed for immunohistochemistry staining and western blotting analysis. RESULTS: There was a significant difference between animals subjected to one day training and those receiving four days of training in escape latency and travel distance. There were an apparent increase in VAChT immunoreactivity in the medial septal area (MSA) and CA1 region of the hippocampus in one day and four day trained animals compared with controls (visible group). Quantitative immunostaining analysis by optical density measurements in the CA1 region and evaluation of immunopositive neurons in medial septal area of brain sections confirmed qualitative findings. Assessment of VAChT protein level expression in hippocampus by western blotting evaluation showed the same pattern of immunohistochemistry results. CONCLUSION: Overall, results of this study reveal changes in cholinergic neuron activity in different stages of training in the MWM task. Data suggest that there is a significant level of cholinergic neuronal activity during early stages of the training especially in the hippocampus region that may contribute to the apparent increase in VAChT expression.