fatema pirsalami

Previous studies have shown that converting curcumin into nanoparticles can enhance its therapeutic effect in models of convulsion. Changes in calmodulin-dependent Ca2+/protein kinase (CaMKII) are associated with some experimental models of epilepsy. This study aimed to evaluate the hippocampal CaMKII phosphorylation following the therapeutic effect of nanocurcumin in a model of pentylenetetrazole (PTZ)-induced convulsion.

Nanocurcumin (with an average particle diameter of 150 nm) was produced using bovine serum albumin and was administered orally (gavage) to male NMRI mice weighing 25-30 g at doses of 50 and 100 mg/kg. One hour later, PTZ at a dose of 85 mg/kg was administered intraperitoneally to the animal. Following intraperitoneal PTZ injection, the latency of myoclonus, clonus, general tonic convulsion, and mortality rate were recorded in male mice. After behavioral testing, the anesthetized animals were euthanized, and the levels of phosphorylated and total forms of hippocampal CaMKII were determined by Western blotting technique.

The results showed that oral administration of nanocurcumin at doses of 50 and 100 mg/kg significantly improved convulsion induced by PTZ compared with natural curcumin. In all groups, convulsion increased hippocampal CaMKII phosphorylation, and nanocurcumin did not modulate it.

The findings of this study showed that the therapeutic effect of nanocurcumin in a model of pentylenetetrazole-induced convulsion was not associated with a change in hippocampal CaMKII activity pattern.

Edaravone is an anti-stroke medication that may have nitric oxide (NO) modulating properties. This study evaluated the role of NO in the acute and sub-chronic anticonvulsant effects of edaravone in murine models of seizures induced by intraperitoneal (IP) or intravenous (IV) injections of pentylenetetrazole (PTZ) or electroshock (maximal electroshock seizure [MES]). 132 male albino mice were randomly divided into 22 groups (n=6) and given IP injections of vehicle or edaravone either acutely or for eight days (sub-chronically). The seizure was induced by electroshock or PTZ (IP or IV). The following edaravone doses were used: 7.5, 10, 12.5 (acute); 5, 7.5, 10 (sub-chronic) in IP PTZ model; 5, 7.5, 10 in IV PTZ model; and 5, 10 mg/Kg in the MES. To evaluate NO involvement, 216 mice were randomly divided into 36 groups (n=6) and pretreated with vehicle, edaravone, a non-specific nitric oxide synthase (NOS) inhibitor: N(ω)-nitro-L-arginine methyl ester (L-NAME) (5 mg/Kg), a specific nNOS inhibitor: 7-nitroindazole (7-NI) (60 mg/Kg), or a combination of edaravone plus L-NAME or 7-NI, either acutely or for eight days before seizure induction. Doses of edaravone were as follows: in IP PTZ model: 12.5 (acute) and 10 (sub-chronic); in IV PTZ model: 10; and in the MES: 5 mg/Kg. Data were analyzed using the one-way analysis of variance (ANOVA) followed by Tukey’s test (SPSS 18). P≤0.05 was considered statistically significant. In the IP PTZ model, edaravone increased time latencies to seizures (P<0.001), prevented tonic seizures, and death. Edaravone increased the seizure threshold (P<0.001) in the IV PTZ model and shortened the duration of tonic hind-limb extension (THE) in the MES model (P<0.001). In comparison to mice treated with edaravone alone, adding L-NAME or 7-NI reduced seizure time latencies (P<0.001), reduced seizure threshold (P<0.001), and increased THE duration (P<0.001). Edaravone (acute or sub-chronic) could prevent seizures by modulating NO signaling pathways.

Edaravone is a free radical scavenger which is used as a drug for the treatment of cerebral infarction and amyotrophic lateral sclerosis. Edaravone is distributed widely in the body and its effects are not limited to the neural tissue. Many studies indicate that edaravone has some nitric oxide synthase (NOS) modulating properties. In this research we evaluated the effects of edaravone (1, 5 and 10 mg/kg) alone or in concombination with diphenyliodonium chloride (a specific endothelial NOS inhibitor) or aminoguanidine (a specific inducible NOS inhibitor) on oxidative stress, and renal tissue and function in a model of acute kidney injury induced by a single intramuscular injection of hypertonic glycerol solution. Effects of edaravone on gene expressions of eNOS and iNOS (by RT-PCR) were also investigated. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s test. At the end of this study, edaravone attenuated oxidative stress and improved renal tissue damage and dysfunction. Aminoguanidine enhanced the renoprotective effects of edaravone. Edaravone showed no remarkable effect on the expression of eNOS gene but it reduced the induction of iNOS gene significantly. The results of this study showed that edaravone could protect against rhabdomyolysis-induced acute kidney injury using its antioxidant activity and inhibiting effect on iNOS gene expression.

Although several animal studies have indicated the antiepileptic effect for curcumin, there are reports stating the null antiepileptic effect of this substance. This inconsistency might be due to the low bioavailability of curcumin. Therefore, the current study aimed to assess the effect of oral bovine serum albumin (BSA)-based nanocurcumin on seizure caused by pentylenetetrazol (PTZ) in mice. Furthermore, due to the suggested involvement of JNK signaling in seizure pathology, the hippocampal pattern of JNK phosphorylation (activation) was evaluated.

BSA based nanocurcumin was administered at doses of 50 and 100mg/kg oral gavage to male NMRI mice, one hour before PTZ administration. Intravenous PTZ paradigm was used to determine the threshold dose of PTZ to induce clonic seizures, while the intraperitoneal PTZ paradigm was applied to evaluate the latency for appearance of generalized clonus. Upon completion of intraperitoneal PTZ paradigm experiments, the hippocampi were removed and Western blot analysis was performed to determine the phosphorylated and total forms of JNK.

The results indicated that BSA-based nanocurcumin at the doses of 50 and 100mg/kg could significantly increase the threshold and latency of clonic seizure, which was a significant superior effect compared to natural curcumin. PTZ significantly increased the level of hippocampal JNK phosphorylation, but pretreatment of nanocurcumin did not modify this effect.

The present study shows that converting curcumin to BSA-based nanocurcumin can increase its antiepileptic effect. Furthermore, the antiepileptic effect of nanocurcumin was not associated with a modification in PTZ-induced hippocampal JNK hyper activation.

There is evidence indicating that the rate of AD is lower in curry consuming populations. Then, there is an effort to elucidate if curcumin -as the main ingredient of turmeric- might affect the process of AD. However, in clinical trials of AD, a six-month curcumin treatment failed to show any progress, which might be attributable to its low bioavailability. In this line, a recent human study revealed that a more bioavailable solid lipid curcumin enhances cognition in aged adults. By the application of Bovine Serum Albumin (BSA), the current study aimed at converting curcumin to nano sizes and assessing its protective effects against scopolamine-induced passive avoidance memory retrieval deficit. Nanocurcumin was prepared via dissolution method. Male NMRI mice (20-25 g body weight) were used. The effective doses of nanocurcumin were selected according to the initial pilot test. The mice were treated with nanocurcumin 15 or 20 mg/kg/p.o or distilled water for 10 days. The animals were habituated and trained in passive avoidance apparatus on the day 10. The retention test was performed 24 hours later. Scopolamine (1 mg/kg/i.p.) or saline was injected 30 minutes before memory retention trial. The findings indicated that nanocurcumin in doses 15 or 20 mg/kg/p.o prevented the retrieval deficit induced by scopolamine while natural curcumin in its equivalent doses did not have such an effect. Furthermore, nanocurcumin by itself improved memory retention comparing with the control group.  These findings implied that the potential anti-amnesic effects of curcumin might be observed by producing and using its nanoformulation form.

Cyclosporine A (CsA) is an immunosuppressant with therapeutic indications in various immunological diseases; however, its use is associated with chronic nephropathy. Oxidative stress has a crucial role in CsA-induced nephrotoxicity. The present study evaluates the protective effect of edaravone on CsA-induced chronic nephropathy and investigates its antioxidant and nitric oxide modulating property.
Male Sprague-Dawley rats (n=66) were distributed into nine groups, including a control (group 1) (n=7). Eight groups received CsA (15 mg/kg) for 28 days while being treated. The groups were categorized as:•Group 2: Vehicle (n=10)
•Groups 3, 4, and 5: Edaravone (1, 5, and 10 mg/kg) (n=7 each)
•Group 6: Diphenyliodonium chloride, a specific endothelial nitric oxide synthase (eNOS) inhibitor (n=7)
•Group 7: Aminoguanidine, a specific inducible nitric oxide synthase (iNOS) inhibitor (n=7)
•Group 8: Edaravone (10 mg/kg) plus diphenyliodonium chloride (n=7)
•Group 9: Edaravone (10 mg/kg) plus aminoguanidine (n=7)
Blood urea nitrogen and serum creatinine levels, malondialdehyde, superoxide dismutase, and glutathione reductase enzyme activities were measured using standard kits. Renal histopathological evaluations and measurements of eNOS and iNOS gene expressions by RT-PCR were also performed. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s test (SPSS software version 18.0).
Edaravone (10 mg/kg) significantly attenuated CsA-induced oxidative stress, renal dysfunction, and kidney tissue injury. Aminoguanidine improved the renoprotective effect of edaravone. Edaravone reduced the elevated mRNA level of iNOS, but could not alter the level of eNOS mRNA significantly.
Edaravone protects against CsA-induced chronic nephropathy using antioxidant property and probably through inhibiting iNOS gene expression.