Therapeutic effects of carvacrol on beta-amyloid-induced impairments in in vitro and in vivo models of Alzheimer's disease.

Due to the complex nature of Alzheimer's disease (AD), it is important to investigate agents with multiple effects in the treatment of AD. Carvacrol possesses anti-acetylcholinesterase, anti-oxidant, and neuroprotective properties. We therefore investigated therapeutic effects of carvacrol on cell viability, oxidative stress, and cognitive impairment in Aß1-42-induced in vitro and in vivo models of AD. SH-SY5Y cells differentiated into neurons by retinoic acid were pretreated with carvacrol or galantamine before Aß1-42 administration. For in vivo experiments, a rat model of AD was established by bilateral intrahippocampal injection of Aß1-42. The groups received 1% DMSO, carvacrol, or galantamine intraperitoneally twice a day (morning and afternoon) for 6 days. Cell viability was determined using MTT and LDH tests. Learning and memory functions were assessed using a passive-avoidance test. Oxidant-antioxidant parameters (MDA, H2 O2 , SOD, and CAT) and Tau, Aß1-40, and Aß1-42 peptide levels in in vitro supernatant or in vivo serum and hippocampal samples were measured using ELISA. Carvacrol increased cell viability and exhibited a protective effect against oxidative stress by preventing Aß1-42-induced cytotoxicity, LDH release, and increments in MDA and H2 O2 levels in vitro. Additionally, it improved memory impairment by reversing Aß1-42-induced changes on passive-avoidance test. Carvacrol ameliorated Aß1-42-induced increments in MDA and H2 O2 levels in in vitro supernatant and in vivo hippocampal samples. However, none of the treatments changed in vitro SOD and Tau-peptide levels, or in vivo serum levels of MDA, H2 O2 , SOD, CAT, Tau peptide, Aß1-40, or Aß1-42. Our results suggest that multi-target pharmacological agent carvacrol may be promising in treatment of AD by preventing beta-amyloid-induced neurotoxicity, oxidative stress, and memory deficits.

Effects of thymoquinone, the major constituent of Nigella sativa seeds, on penicillin-induced epileptiform activity in rats.

OBJECTIVE: To investigate the effects of thymoquinone (TQ) in a penicillin-induced epilepsy model in rats. METHODS: This experimental study included 56 adult male Wistar rats. Experiments were performed in the Research Laboratory of the Department of Physiology, Medical School, Duzce University, Duzce, Turkey, between October 2013 and December 2014. Animals were divided into the following 7 groups: sham, control, only thymoquinone, vehicle (Dimethylsulfoxide), and doses of 10, 50, and 100 mg/kg of TQ. After rats were anesthetized, the left part of the skull was removed. A pair of silver/silver chloride electrodes was placed on the somatomotor area, and electrocorticographic recording was started. After 5 minutes basal activity was recorded, and TQ was applied intraperitoneally. At the thirtieth minute after TQ, epileptiform activity was induced by intracortical penicillin. The first spike latency, spike frequency, and the amplitude of epileptiform activity were analyzed statistically. RESULTS: The different doses of TQ significantly increased the latency time to onset of first spike wave, and decreased the frequency, and amplitude of epileptiform activity in the first 20 minutes compared with the control group. CONCLUSION: Thymoquinone shows potential as an antiepileptic drug resulting from its effects of prolonged latency time, and reduced spike wave frequency and amplitude of epileptiform activity.

In vivo comparison of the effects of bupivacaine and levobupivacaine on the pregnant rat myometrium using electrohysterogram.

BACKGROUND AND AIMS: The effect of local anesthetics on myometrial contractility during labor analgesia is debatable. We aimed to compare the effects of bupivacaine and levobupivacaine on rat uterine contractility in an in vivo setting. METHODS: Electrical activities of 40 pregnant rat uteruses were recorded on electrohysterogram after dividing the rats into bupivacaine and levobupivacaine groups. Uterine contraction frequencies were recorded at each 5-min interval. The first 5-min recording was considered the control, which was immediately followed by intramyometrial administration of either bupivacaine or levobupivacaine. The recordings were continued for 30 min. The changes in frequencies at each time interval of the groups were compared with each other and the control recording. RESULTS: The frequencies from both groups at each interval were lower than the control values, but not different between the groups. The frequencies of the bupivacaine group during the 5-10 min and 10-15 min intervals were lower than the control time interval, but no significant differences were present between the control and the other time intervals. However, no significant differences were found at any time interval for the levobupivacaine group. CONCLUSION: Levobupivacaine led to less muscle relaxation compared to bupivacaine and may be a better option for labor analgesia and anesthesia considering uterine contractility.

Prophylactic selective laser trabeculoplasty in the prevention of intraocular pressure elevation after intravitreal triamcinolone acetonide injection.

PURPOSE: To evaluate the prophylactic efficacy of selective laser trabeculoplasty for preventing an increase in intraocular pressure (IOP) after intravitreal triamcinolone acetonide injection. DESIGN: Prospective, comparative, interventional case series. METHODS: We studied 31 eyes with a baseline IOP of 21 mm Hg or more of 31 patients for which intravitreal triamcinolone acetonide injection was planned for diabetic macular edema. The patients were divided into 2 groups, a study group and control group. The study group comprised 15 eyes of 15 patients that underwent selective laser trabeculoplasty a mean of 8.3 ± 4.1 days before intravitreal triamcinolone acetonide injection. The control group comprised 16 eyes of 16 patients who underwent only intravitreal triamcinolone acetonide injection. Main outcomes measures were mean IOP and number of patients requiring antiglaucomatous therapy. RESULTS: Mean baseline IOP was 21.6 ± 0.9 mm Hg in the study group and 21.5 ± 0.8 mm Hg in the control group (P = .98). Mean IOP at 1 day after injection was 17.0 ± 2.0 mm Hg in the study group and 19.5 ± 4.3 mm Hg in the control group (P = .23). Mean IOP at 1 week after injection was 16.9 ± 1.7 mm Hg and 18.4 ± 4.0 mm Hg, respectively (P = .49); mean IOP at 1 month after injection was 16.4 ± 1.5 mm Hg and 20.8 ± 5.6 mm Hg, respectively (P = .003); mean IOP at 3 months after injection was 15.8 ± 2.5 mm Hg and 18.3 ± 5.5 mm Hg, respectively (P = .01); and mean IOP at 6 months after injection was 15.7 ± 1.4 mm Hg and 17.1 ± 1.5 mm Hg, respectively (P = .03). The number of patients requiring antiglaucomatous therapy during follow-up was 0 of 15 eyes in the study group and 8 of 16 eyes in the control group (P = .001). CONCLUSIONS: The IOP elevation after intravitreal triamcinolone acetonide injection may be prevented by performing selective laser trabeculoplasty before intravitreal triamcinolone acetonide injection, especially in cases with a baseline IOP of 21 mm Hg or more.

The effect of intra-arterial papaverine on ECoG activity in the ketamine anesthetized rat.

The opium alkaloid papaverine (PPV) causes vasodilatation of the cerebral arteries through direct action on smooth muscle that reduces the constriction of smooth muscle. Intra-arterial papaverine (IAP) has been used widely to increase the regional cerebral blood flow in order to reverse the cerebral vasospasm that occurs during endovascular procedures. IAP-induced seizures have been reported, although PPV has anticonvulsive effects. This study determined the effects of IAP on electrocorticography (ECoG) in the ketamine anesthetized rats. We used 24 Sprague-Dawley male rats weighing 200-250 g. The animals were divided randomly into four groups: three treatment groups (groups 1-3) and a control (group 4). Groups 1, 2, and 3 were given 1, 7, and 14 mg/kg IAP, respectively. The ECoG was compared across groups. Our results indicated that IAP did not cause seizures and that it decreased the frequency of ketamine-induced epileptiform activity in the 14 mg/kg group.

Protective effects of cysteine, methionine and vitamin C on the stomach in chronically alcohol treated rats.

A chronic intake of high dose alcohol may cause oxidative stress and inflammation in the stomach. It is hypothesized that cysteine-methionine and vitamin C may neutralize harmful compounds while potentiating the antioxidant capacity of the cell or tissue. The experimental animals were fed regular diets and were maintained for 90 days in the control group, the alcoholic group, which was given 2.5 g of 50% ethanol kg(-1) body wt. administered intragastrically every other day, or the alcoholic with antioxidant supplement group, to whom 2.5 g of 50% ethanol kg(-1) body wt. + a solution that contained 200 mg vitamin C, 100 mg cysteine and 100 mg methionine was administered intragastrically every other day. After the treatments, the stomach was taken for pathological and biochemical analysis. The stomach of the alcoholic group rats had higher scores of pathological findings compared with the control group, whereas the scores of the antioxidant-supplemented group were lower than the alcoholic group. In addition, the oxidized protein and lipid content in the stomachs of the alcoholic group were significantly higher than the control, but antioxidant supplementation lowered the amount of oxidation in the antioxidant supplemented group. The amount of stomach glutathione in the alcoholic group was higher than that of the control and antioxidant-supplemented groups. Interestingly, the level of total thiol in the stomach tissue of rats with antioxidant supplement was statistically higher than that of the control and alcoholic groups. In conclusion, the scores of the pathological findings in the stomach of rats with the antioxidant supplement were lower than the chronic alcohol-treated rats, albeit the amount of total thiol was increased in this group. Moreover, chronic alcohol treatment led to an increase in the level of lipid and protein oxidation in the stomach tissue of rats. A simultaneous intake of ascorbate/l-cys/l-met along with ethanol attenuated the amount of oxidation which suggested that cysteine-methionine and vitamin C could play a protective role in the stomach against oxidative damage resulting from chronic alcohol ingestion.

Alcohol-induced oxidative stress and reduction in oxidation by ascorbate/L-cys/ L-met in the testis, ovary, kidney, and lung of rat.

Chronic exposure to high doses of alcohol results in many pathophysiologic changes in cellular function caused by the alcohol itself and the effects of its metabolism (ie, generation of acetaldehyde, nicotinamide adenine dinucleotide [NADH], free radicals, and oxidative stress). However, the role of each of these effects on the testis, ovary, kidney, and lung in chronic alcoholism must be investigated. It is hypothesized that cysteine-methionine and vitamin C might neutralize harmful compounds and potentiate the antioxidant capacity of the cell or tissue. In this study, rats were fed regular diets and were maintained in the following groups for 90 days: control group; alcoholic group (2.5 g of 50% ethanol/kg body wt administered intragastrically every other day); and alcoholic with antioxidant supplement group (2.5 g of 50% ethanol plus a solution containing 200 mg vitamin C, 100 mg cysteine, and 100 mg methionine/kg body wt administered intragastrically every other day). After treatment had been completed, rat blood, testis, ovary, kidney, and lung were taken for biochemical analysis. Mean alcohol level in the alcoholic group was raised (by 40%) compared with that in the control group, but it was lower (by 30%) in the antioxidant-supplemented group than in the alcoholic group. In accordance with the levels of alcohol, oxidized protein and lipid content in the testis, ovary, kidney, and lung were low in the control group, higher in the antioxidant-supplemented group, and highest in the alcoholic group. It is interesting to note that levels of glutathione in the testis and lung of the alcoholic group were lower than those in both the control and antioxidant-supplemented groups. In conclusion, chronic alcohol administration led to a significant increase in the level of protein oxidation in the ovary and kidney of rats. Simultaneous intake of ascorbate/L-cys/L-met, along with ethanol, partly attenuated the amount of lipid and protein oxidation that occurred in tissues with oxidative stress caused by alcohol consumption.

The effects of ethanol consumption on the lipid peroxidation and glutathione levels in the right and left brains of rats.

The effects of ethanol consumption on the levels of lipid peroxidation and reduced glutathione (GSH) in the cerebral hemispheres of male rats were investigated. The rats were randomly divided into eight groups: control, 10%, 25%, 35% ethanol-consuming groups, and four groups given vitamin E. The level of lipid peroxidation increased 34.32% (right brain), 35.67% (left brain) in 10% ethanol-consuming rats; 32.05% (right brain), 31.81% (left brain) in 25% ethanol-consuming rats; and 33.45% (right brain), 39.72% (left brain) in 35% ethanol-consuming rats. The GSH level of the right and left brains significantly decreased: 19.39%, 19.56%; 27.58%, 29.34%; 35.34%, 33.22% in rats consuming 10%, 25%, and 35% ethanol, respectively. These effects were partly antagonized by administration of vitamin E (100 mg/kg/day i.p.) to ethanol-consuming rats for 20 days. The results suggested that the cerebral hemispheres of adult rats are susceptible to the oxidative neurotoxic effects of ethanol, which may be blocked by vitamin E.

Further evidence for enhancing effects of NO on monosynaptic and polysynaptic spinal reflexes in cats.

There are a number of studies on the effects of different NO donors and inhibitors on spinal cord with quite contradictory results. The aim of this study was to investigate the effects of sodium nitroprusside (SNP), a NO donor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor, on monosynaptic and polysynaptic spinal reflexes in anesthetized and spinalized cats. After a dorsal laminectomy between L5 and S1, monosynaptic and polysynaptic spinal reflexes were evoked by stimulation of gastrocnemius nerves. Following control recordings, administration of L-NAME in 100, 200, 500 microM (local) and 10, 20, 50 mg/kg (i.v.) doses decreased significantly the monosynaptic and polysynaptic reflex amplitudes in a dose-dependent manner. Administration of SNP in 100, 200, 500 microM (local) and 100, 200, 500 microg/kg (i.v.) doses enhanced significantly the both reflex amplitudes in a dose-dependent manner. In another series of experiments it has been observed that the maximal decrease in reflex amplitudes caused by 500 microM local L-NAME administration in the 15th minute was reversed by locally administered SNP (500 microM). Our results support the hypothesis stating that NO may play a role in the modulation of mono- and polysynaptic spinal reflexes and the NO appears to have an enhancing role on these responses.