Cardioprotective effect of Vitamin D on cardiac hypertrophy through improvement of mitophagy and apoptosis in an experimental rat model of levothyroxine -induced hyperthyroidism.

BACKGROUND: Mitochondria are known to be involved in mediating the calorigenic effects of thyroid hormones. With an abundance of these hormones, alterations in energy metabolism and cellular respiration take place, leading to the development of cardiac hypertrophy. Vitamin D has recently gained attention due to its involvement in the regulation of mitochondrial function, demonstrating promising potential in preserving the integrity and functionality of the mitochondrial network. The present study aimed to investigate the therapeutic potential of Vitamin D on cardiac hypertrophy induced by hyperthyroidism, with a focus on the contributions of mitophagy and apoptosis as possible underlying molecular mechanisms. METHODS AND RESULTS: The rats were divided into three groups: control; hyperthyroid; hyperthyroid + Vitamin D. Hyperthyroidism was induced by Levothyroxine administration for four weeks. Serum thyroid hormones levels, myocardial damage markers, cardiac hypertrophy indices, and histological examination were assessed. The assessment of Malondialdehyde (MDA) levels and the expression of the related genes were conducted using heart tissue samples. Vitamin D pretreatment exhibited a significant improvement in the hyperthyroidism-induced decline in markers indicative of myocardial damage, oxidative stress, and indices of cardiac hypertrophy. Vitamin D pretreatment also improved the downregulation observed in myocardial expression levels of genes involved in the regulation of mitophagy and apoptosis, including PTEN putative kinase 1 (PINK1), Mitofusin-2 (MFN2), Dynamin-related Protein 1 (DRP1), and B cell lymphoma-2 (Bcl-2), induced by hyperthyroidism. CONCLUSIONS: These results suggest that supplementation with Vitamin D could be advantageous in preventing the progression of cardiac hypertrophy and myocardial damage.

Neuroprotective effects of vinpocetine, as a phosphodiesterase 1 inhibitor, on long-term potentiation in a rat model of Alzheimer's disease.

BACKGROUND: Vinpocetine (Vin) is known as a phosphodiesterase 1 inhibitor (PDE1-I) drug with multilateral effects, including antioxidant and anti-inflammatory activity. In this research, we investigated the neuroprotective and therapeutic effects of Vin through hippocampal synaptic plasticity on a rat's model of Alzheimer's disease (AD) induced by an intracerebroventricular (ICV) injection of beta-amyloid (Aß). METHODS: Sixty adult male Wistar rats were randomly divided into six groups: 1. control, 2. sham, 3. Aß, 4. pretreatment (Vin + Aß): Vin (4 mg/kg, gavage) for 30 days and then, inducing an AD model by an ICV injection of Aß(1-42), 5. treatment (Aß + Vin): inducing an AD model and then receiving Vin for 30 days by gavage, and 7. pretreatment + treatment (Vin + Aß + Vin): receiving Vin by gavage for 30 days before and 30 days after the induction of an AD model. After these procedures, via stereotaxic surgery, the stimulating electrodes were placed at the perforant pathway (PP) and the recording electrodes were implanted in the dentate gyrus. RESULTS: Excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the Aß group meaningfully diminished compared to the control group after the induction of long-term potentiation (LTP). CONCLUSIONS: Vin could significantly prevent the Aß effects on LTP. It can be concluded that pretreatment and treatment with Vin can be neuroprotective against harmful consequences of Aß on hippocampal synaptic plasticity.

Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging.

BACKGROUND: Aging is a main risk factor for the development of cardiovascular diseases (CVDs). Gallic acid (GA) is a phenolic compound derived from a wide range of fruits. GA has a wide spectrum of pharmacological properties, including anti-oxidative, anti-inflammatory, and cardioprotective effects. This research was conducted to determine the cardioprotective effect of GA on cardiac hypertrophy in aged rats. METHODS AND RESULTS: Following histological evaluation and through observing the heart, we found that GA improved the cardiac hypertrophy induced by D-galactose (D-GAL) in cardiac cells. To clarify the causes for this anti-aging effect, we evaluated the malonic dialdehyde levels and antioxidant enzyme activity in rat cardiac tissue. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in serum were measured. The levels of genes related to mitochondrial biogenesis, mitophagy, and apoptosis in cardiac tissue were surveyed. The findings represented that GA ameliorated antioxidant enzyme activity while significantly decreasing the malonic dialdehyde levels. Real-time PCR analysis proposed that GA effectively improved mitochondrial biogenesis in the heart via regulating the expression levels of Sirtuin 1 (SIRT1), PPARγ coactivator 1α (PGC1-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). GA also mitigated apoptosis in the heart by modulating the expression levels of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X (Bax). In addition, GA improved serum LDH and CK-MB levels. CONCLUSIONS: GA may alleviate aging-induced cardiac hypertrophy via anti-oxidative, mitoprotective, and anti-apoptotic mechanisms.

Royal jelly improves learning and memory deficits in an amyloid ß-induced model of Alzheimer's disease in male rats: Involvement of oxidative stress.

Alzheimer's disease (AD) as the commonest type of dementia is associated with the cognitive function failure. Oxidative stress performs an essential role in the progression of AD. Royal jelly (RJ) is a natural product of bees with antioxidant and anti-inflammatory properties. The present research aimed to investigate the possible protective effect of RJ on learning and memory in a rat model of Aß-induced AD. Forty male adult Wistar rats were equally distributed into five groups: control, sham-operated, Aß (receiving intracerebroventricular (ICV) injection of amyloid beta (Aß1-40)), Aß + RJ 50 mg/kg, and Aß + RJ 100 mg/kg. RJ was administered daily post-surgery by oral gavage for four weeks. Behavioral learning and memory were examined using the novel object recognition (NOR) and passive avoidance learning (PAL) tests. Also, oxidative stress markers, such as malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant capacity (TAC), were assessed in the hippocampus. Aß reduced step-through latency (STLr) and increased time spent in the dark compartment (TDC) in the PAL task and also decreased discrimination index in the NOR test. Administration of RJ ameliorated the Aß-related memory impairment in both NOR and PAL tasks. Aß decreased TAC and increased MDA and TOS levels in the hippocampus, whereas RJ administration reversed these Aß-induced alterations. Our results indicated that RJ has the potential to ameliorate learning and memory impairment in the Aß model of AD via attenuating oxidative stress.

Influence of hippocampal GABAB receptor inhibition on memory in rats with acute ß-amyloid toxicity.

The neurotransmitter γ-aminobutyric acid (GABA) is involved in the process of memory. It has been reported that the inhibition of GABAB receptors has beneficial effects on cognition. The aim of this study was to investigate the role of CGP35348 (a GABAB receptor antagonist) on dentate gyrus GABAB receptor inhibition and its effects on learning and memory impairments that had been induced in adult male rats by microinjection of ß-amyloid (Aß). Seventy Wistar male rats were randomly divided into seven groups: control, sham (receiving the Aß vehicle only), Aß, Aß + CGP35348 (1, 10, and 100 µg/µL), and CGP35348 alone (10 µg/µL). Memory impairment was induced by unilateral interventricular microinjection of Aß (6 µg/6 µL). Rats were cannulated bilaterally in the dentate gyrus, and then, they were treated for 20 consecutive days. Learning and memory were assessed using the novel object recognition and passive avoidance learning tests. The discrimination index and the step-through latency were significantly increased in the Aß + CGP35348 group in comparison to the Aß only group (P < 0.05 and P < 0.01, respectively). Data showed that the discrimination index was decreased in the Aß + CGP35348 group in comparison with the control group (P < 0.05) and sham group (P < 0.01). Moreover, the step-through latency was significantly decreased in the Aß + CGP35348 group in comparison to the control and sham groups (P < 0.01). Data from this study indicated that intra-hippocampal microinjection of the GABAB receptor antagonist counteracts the learning, memory, and cognitive impairments induced by Aß. It can be concluded that the GABAB receptor antagonist is a possible therapeutic agent against the progression of acute Aß toxicity-induced memory impairment.

Antidiabetic potential of salvianolic acid B in multiple low-dose streptozotocin-induced diabetes.

CONTEXT: Salvianolic acids are the most abundant water-soluble compounds extracted from the herb Salvia miltiorrhiza L. (Lamiaceae) with antioxidant and protective effects. OBJECTIVE: This study evaluates the antidiabetic effect of salvianolic acid B (Sal B) in multiple low-dose streptozotocin (MLDS)-induced diabetes in rat. MATERIALS AND METHODS: Rats were divided into control, Sal B40-treated control, diabetic, Sal B20-, and Sal B40-treated diabetic groups. Sal B was daily administered at doses of 20 or 40 mg/kg (i.p.), started on third day post-STZ injection for 3 weeks. Serum glucose and insulin level and some oxidative stress markers in pancreas were measured in addition to the oral glucose tolerance test (OGTT), histological assessment, and apoptosis determination. RESULTS: After 3 weeks, treatment of diabetic rats with Sal B20 and Sal B40 caused a significant decrease of the serum glucose (p < 0.05-0.01) and improvement of OGTT. Meanwhile, serum insulin was significantly higher in Sal B20- and Sal B40-treated diabetics (p < 0.01) and treatment of diabetics with Sal B40 significantly lowered malondialdehyde (MDA) (p < 0.05), raised glutathione (GSH) (p < 0.05), and activity of catalase (p < 0.01) with no significant change of nitrite. Furthermore, the number of pancreatic islets (p < 0.05) and their area (p < 0.01) was significantly higher and apoptosis reactivity was significantly lower (p < 0.05) in the Sal B40-treated diabetic group versus diabetics. DISCUSSION AND CONCLUSION: Three-week treatment of diabetic rats with Sal B exhibited antidiabetic activity which is partly exerted via attenuation of oxidative stress and apoptosis and augmentation of antioxidant system.

Effect of diminazene on cardiac hypertrophy through mitophagy in rat models with hyperthyroidism induced by levothyroxine.

Hyperthyroidism is associated with the alteration in molecular pathways involved in the regulation of mitochondrial mass and apoptosis, which contribute to the development of cardiac hypertrophy. Diminazene (DIZE) is an animal anti-infection drug that has shown promising effects on improving cardiovascular disease. The aim of the present study was to investigate the therapeutic effect of DIZE on cardiac hypertrophy and the signaling pathways involved in this process in the hyperthyroid rat model. Twenty male Wistar rats were equally divided into four groups: control, hyperthyroid, DIZE, and hyperthyroid + DIZE. After 28 days of treatment, serum thyroxine (T4) and thyroid stimulating hormone (TSH) level, cardiac hypertrophy indices, cardiac damage markers, cardiac malondialdehyde (MDA), and superoxide dismutase (SOD) level, the mRNA expression level of mitochondrial and apoptotic genes were evaluated. Hyperthyroidism significantly decreased the cardiac expression level of SIRT1/PGC1α and its downstream involved in the regulation of mitochondrial biogenesis, mitophagy, and antioxidant enzyme activities including TFAM, PINK1/MFN2, Drp1, and Nrf2, respectively, as well as stimulated mitochondrial-dependent apoptosis by reducing Bcl-2 expression and increasing Bax expression. Treatment with DIZE significantly reversed the downregulation of SIRT1, PGC1α, PINK1, MFN2, Drp1, and Nrf2 but did not significantly change the TFAM expression. Moreover, DIZE suppressed apoptosis by normalizing the cardiac expression levels of Bax and Bcl-2. DIZE is effective in attenuating hyperthyroidism-induced cardiac hypertrophy by modulating the mitophagy-related pathway, suppressing apoptosis and oxidative stress.

Geraniol improves passive avoidance memory and hippocampal synaptic plasticity deficits in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is the most progressive and irreversible neurodegenerative disease that leads to synaptic loss and cognitive decline. The present study was designed to evaluate the effects of geraniol (GR), a valuable acyclic monoterpene alcohol, with protective and therapeutic effects, on passive avoidance memory, hippocampal synaptic plasticity, and amyloid-beta (Aß) plaques formation in an AD rat model induced by intracerebroventricular (ICV) microinjection of Aß1-40. Seventy male Wistar rats were randomly into sham, control, control-GR (100 mg/kg; P.O. (orally), AD, GR-AD (100 mg/kg; P.O.; pretreatment), AD-GR (100 mg/kg; P.O.; treatment), and GR-AD-GR (100 mg/kg; P.O.; pretreatment & treatment). Administration of GR was continued for four consecutive weeks. Training for the passive avoidance test was carried out on the 36th day and a memory retention test was performed 24 h later. On day 38, hippocampal synaptic plasticity (long-term potentiation; LTP) was recorded in perforant path-dentate gyrus (PP-DG) synapses to assess field excitatory postsynaptic potentials (fEPSPs) slope and population spike (PS) amplitude. Subsequently, Aß plaques were identified in the hippocampus by Congo red staining. The results showed that Aß microinjection increased passive avoidance memory impairment, suppressed of hippocampal LTP induction, and enhanced of Aß plaque formation in the hippocampus. Interestingly, oral administration of GR improved passive avoidance memory deficit, ameliorated hippocampal LTP impairment, and reduced Aß plaque accumulation in the Aß-infused rats. The results suggest that GR mitigates Aß-induced passive avoidance memory impairment, possibly through alleviation of hippocampal synaptic dysfunction and inhibition of Aß plaque formation.

Effectiveness of coenzyme Q10 on learning and memory and synaptic plasticity impairment in an aged Aß-induced rat model of Alzheimer's disease: a behavioral, biochemical, and electrophysiological study.

RATIONALE: Aging is the major risk factor for Alzheimer's disease (AD), and cognitive and memory impairments are common among the elderly. Interestingly, coenzyme Q10 (Q10) levels decline in the brain of aging animals. Q10 is a substantial antioxidant substance, which has an important role in the mitochondria. OBJECTIVE: We assessed the possible effects of Q10 on learning and memory and synaptic plasticity in aged ß-amyloid (Aß)-induced AD rats. METHODS: In this study, 40 Wistar rats (24-36 months old; 360-450 g) were randomly assigned to four groups (n = 10 rats/group)-group I: control, group II: Aß, group III: Q10; 50 mg/kg, and group IV: Q10+Aß. Q10 was administered orally by gavage daily for 4 weeks before the Aß injection. The cognitive function and learning and memory of the rats were measured by the novel object recognition (NOR), Morris water maze (MWM), and passive avoidance learning (PAL) tests. Finally, malondialdehyde (MDA), total antioxidant capacity (TAC), total thiol group (TTG), and total oxidant status (TOS) were measured. RESULTS: Q10 improved the Aß-related decrease in the discrimination index in the NOR test, spatial learning and memory in the MWM test, passive avoidance learning and memory in the PAL test, and long-term potentiation (LTP) impairment in the hippocampal PP-DG pathway in aged rats. In addition, Aß injection significantly increased serum MDA and TOS levels. Q10, however, significantly reversed these parameters and also increased TAC and TTG levels in the Aß+Q10 group. CONCLUSIONS: Our experimental findings suggest that Q10 supplementation can suppress the progression of neurodegeneration that otherwise impairs learning and memory and reduces synaptic plasticity in our experimental animals. Therefore, similar supplemental Q10 treatment given to humans with AD could possibly provide them a better quality of life.

Protective effects of L-carnitine against valproic acid-induced memory impairment and anxiety-like behavior in adult rat.

This study was designed to explore the effects of valproic acid (VPA) on spatial and passive avoidance learning and memory as well as to assess the protective effects of L-Carnitine (LC) against VPA-induced memory deficit in the rat. Male Wistar rats received VPA (300 mg/kg/daily by i.p. injection), or LC (50 mg/kg/ daily by i.p. injection), or co-treatment with VPA and LC for 28 days. Following 28 days, Elevated Plus-Maze (EPM), Morris Water Maze (MWM), and Passive Avoidance Learning (PAL) tasks were used to evaluate the anxiety-like behavior and spatial and passive learning and memory, respectively. Our results showed that VPA has no effect on memory acquisition (in both MWM and PAL) but induced reference memory impairment. We demonstrated that treatment with LC partially ameliorated the impairment in the retrieval of reference memory and passive avoidance learning. Moreover, VPA increased anxiety-like behavior, which was partially reversed by the administration of LC. In conclusion, these results show that LC is effective in counteracting the anxiety-like behavior and reference memory impairment caused by VPA. Therefore, LC may serve as a possible therapeutic agent for VPA-induced memory change.

Effect of ramosetron, a 5-HT3 receptor antagonist on the severity of seizures and memory impairment in electrical amygdala kindled rats.

The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT3 receptors. Cognitive impairment is common among people with epilepsy. The present study investigated the role of 5-HT3 receptor on the severity of seizures and learning and memory impairment by electrical kindling of amygdala in rats. The amygdala kindling was conducted in a chronic kindling manner in male Wistar rats. In fully kindled animals, ramosetron (as a potent and selective 5-HT3 receptor antagonist) was microinjected unilaterally (ad doses of 1, 10 or 100 µg/0.5 µl) into the EC 5 min before the novel object recognition (NOR) and Y-maze tests or kindling stimulations. Applying ramosetron at the concentration of 100 µg/0.5 µl (but not at 1 and 10 µg/0.5 µl) reduced afterdischarge (AD) duration and increased stage 4 latency in the kindled rats. Moreover, the obtained data from the NOR test showed that treatment by ramosetron (10 and 100 µg/0.5 µl) increased the discrimination index in the fully kindled animals. Microinjection of ramosetron (10 and 100 µg/0.5 µl) in fully kindled animals reversed the kindling induced changes in the percentage of spontaneous alternation in Y-maze task. The findings demonstrated an anticonvulsant role for a selective 5-HT3 receptor antagonist microinjected into the EC, therefore, suggesting an excitatory role for the EC 5-HT3 receptors in the amygdala kindling model of epilepsy. This anticonvulsive effect was accompanied with a restoring effect on cognitive behavior in NOR and Y-maze tests.

The Anti-nociceptive Effect of Ellagic Acid in Streptozotocin-induced Hyperglycemic Rats by Oxidative Stress Involvement.

Introduction: Hyperalgesia is among the current complications of diabetes mellitus; oxidative stress and inflammation were influential in its development. As an herbal component, Ellagic Acid (EA) has some biological activities, including antioxidant and anti-inflammatory effects. This study was designed to evaluate the possible beneficial effect of EA on hypernociception in Streptozotocin (STZ)-induced hyperglycemic rats. Methods: Forty-eight male Wistar rats were divided into the control (receiving vehicle), hyperglycemic, EA (25 mg/kg)-treated control, EA (50 mg/kg)-treated control, EA (25 mg/kg)-treated hyperglycemic, and EA (50 mg/kg)-treated hyperglycemic groups. Hyperglycemia was induced by a single Intraperitoneal (IP) injection of STZ (60 mg/Kg). EA was administered daily by oral gavage for four weeks. The nociceptive response was assessed using Tail-Flick (TF) and Hot-Plate (HP) tests. Also, oxidative stress markers, including Malondialdehyde (MDA), Total Oxidant Status (TOS), and Total Antioxidant Capacity (TAC) in the serum, were evaluated. Results: Hyperglycemic animals were found with significant changes, including a reduction in TF and HP latencies, an elevation in serum MDA level and TOS, and a decrease in serum TAC compared with controls. The treatment of hyperglycemic rats with EA facilitated the reduction of TF latency at the dose of 25 mg/kg and HP latency at 50 mg/kg. Furthermore, EA significantly increased TAC and decreased MDA level at a 50 mg/kg dose and reduced TOS at both doses in the serum of hyperglycemic animals. No significant alterations were found in the parameters studied in EA-treated normal rats. Conclusion: These results displayed the antinociceptive effect of EA in hyperglycemic rats via attenuating oxidative stress. Therefore, EA appears to be a promising agent for managing. Hyperglycemic hypernociception. Highlights: Hyperalgesia is among the current complications of diabetes mellitus.Oxidative stress and inflammation were influential in its development.EA has some biological activities, including antioxidant and anti-inflammatory effects. Plain Language Summary: DN is among the most common chronic complications of diabetes among diabetic patients. DPN is mainly characterized by pain perception alterations, increased sensitivity to mild painful stimuli (hyperalgesia), and abnormal pain sensitivity to stimuli. On the other hand, hyperglycemia by induction of multiple changes, such as fatty acid metabolism abnormalities plays a crucial role in developing DN. Oxidative stress and inflammation are involved in the pathogenesis of DPN. The lack of efficacy and various adverse effects of the current medications for DNP, therefore, new therapeutic candidates are continuously required to improve DNP. Several studies reported the antinociceptive activity of EA in different animal models of pain, such as formalin. Since oxidative stress is involved in diabetic hyperalgesia, compounds with antioxidant properties are good candidates for DN management. Therefore, this research aimed to determine the possible effectiveness of EA and evaluate some oxidative stress-related mechanisms.

Effects of Buprenorphine on the Memory and Learning Deficit Induced by Methamphetamine Administration in Male Rats.

Little is known about the effects of methamphetamine (Meth) and buprenorphine (Bup) on memory and learning in rats. The aim of this investigation was to examine the impact of Meth and Bup on memory and learning. Fourteen male Wistar rats weighing 250-300 g were assigned to four groups: Sham, Meth, Bup, and Meth + Bup and were treated for 1 week. Spatial learning and memory, avoidance learning, and locomotion were assessed using the Morris water maze, passive avoidance learning, and open field tests, respectively. Meth and Bup impaired spatial learning and memory in rats. Co-administration of Meth + Bup did not increase the time spent in the target quadrant compared to Meth alone in the MWM. The Bup and Meh + Bup groups were found with an increase in step-through latency (STLr) and a decrease in the time spent in the dark compartment (TDC). Meth and Bup had no effects on locomotor activity in the open field test. Bup showed a beneficial effect on aversive memory. Since Bup demonstrates fewer side effects than other opioid drugs, it may be preferable for the treatment of avoidance memory deficits in patients with Meth addiction.

The protective and therapeutic effects of vinpocetine, a PDE1 inhibitor, on oxidative stress and learning and memory impairment induced by an intracerebroventricular (ICV) injection of amyloid beta (aß) peptide.

Alzheimer's disease (AD) is a neurodegenerative disease leading to cognitive and memory impairment. This study aimed at investigating the therapeutic and preserving effects of vinpocetine on amyloid beta (Aß)-induced rat model of AD. Sixty male adult Wistar rats were randomly divided into 6 groups (n = 10 per group) as follows: 1; control, 2; sham, 3; Aß, 4; pre-treatment (vinpocetine + Aß): oral gavage administration of vinpocetine at 4 mg/kg for 30 days followed by intracerebroventricular (ICV) injection of Aß, 5; treatment (Aß + vinpocetine): Aß ICV injection followed by vinpocetine administration for 30 days, 6; pre-treatment + treatment (vinpocetine + Aß + vinpocetine): vinpocetine administration for 30 days before and 30 days after AD induction. Following treatments, the animals' learning and memory were investigated using passive avoidance learning (PAL) task, Morris water maze (MWM), and novel object recognition (NOR) tests. The results demonstrated that Aß significantly enhanced escape latency and the distance traveled in the MWM, decreased step-through latency, and increased time spent in the dark compartment in PAL. Vinpocetine ameliorated the Aß-infused memory deficits in both MWM and PAL tests. Administration of vinpocetine in the Aß rats increased the discrimination index of the NOR test. It also significantly diminished the nitric oxide and malondialdehyde levels and restored the reduced glutathione (GSH) levels. Vinpocetine can improve memory and learning impairment following Aß infusion due to its different properties, including antioxidant effects, which indicates that vinpocetine administration can lead to the amelioration of cognitive dysfunction in AD.

Investigation of protective effects of coenzyme Q10 on impaired synaptic plasticity in a male rat model of Alzheimer's disease.

Oxidative stress plays a key role in contributing to ß-amyloid (Aß) deposition in Alzheimer's disease (AD). Coenzyme Q10 (Q10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals. In this study, we investigated the neuroprotective effects of Q10 on Aß-induced impairment in hippocampal long-term potentiation (LTP), a widely researched model of synaptic plasticity, which occurs during learning and memory, in a rat model of AD. In this study, 50 adult male Wistar rats were assigned to five groups: control group (saline); sham group; intraventricular PBS injection, Aß group; intraventricular Aß injection, Q10 group; and Q10 via oral gavage and Q10 + Aß group. Q10 was administered via oral gavage, once a day, for 3 weeks before and 3 weeks after the Aß injection. After the treatment period, in vivo electrophysiological recordings were performed to quantify the excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the hippocampal dentate gyrus. LTP was created by a high-frequency stimulation of the perforant pathway. Following LTP induction, the EPSP slope and PS amplitude were significantly diminished in Aß-injected rats, compared with sham and control rats. Q10 treatment of Aß-injected rats significantly attenuated these decreases, suggesting that Q10 reduces the effects of Aß on LTP. Aß significantly increased serum malondialdehyde levels and total oxidant levels, whereas Q10 supplementation significantly reversed these parameters and increased total antioxidant capacity levels. The present findings suggested that Q10 treatment offers neuroprotection against the detrimental effects of Aß on hippocampal synaptic plasticity via its antioxidant activity.

The sesame lignan sesamin attenuates vascular dysfunction in streptozotocin diabetic rats: involvement of nitric oxide and oxidative stress.

The effect of chronic administration of sesamin was studied on aortic reactivity of streptozotocin diabetic rats. Male diabetic rats received sesamin for 7 weeks after diabetes induction. Contractile responses to KCl and phenylephrine and relaxation response to acetylcholine were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to phenylephrine was significantly lower in sesamin-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine was significantly higher in sesamin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde and decreased superoxide dismutase activity and sesamin treatment significantly improved these changes. Therefore, chronic treatment of diabetic rats with sesamin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and via attenuation of oxidative stress and tissue integrity of endothelium is necessary for its beneficial effect.