Zinc and selenium supplement mitigated valproic acid-induced testis toxicity by modulating the oxidative redox balance in male rats / 대한해부학회지

Valproic acid (VPA) is widely used antiepileptic agent which is associated with reproductive toxicity via impairment in oxidative redox. Zinc (Zn) and selenium (Se) are trace element with antioxidant effect that known to be essential for spermatogenesis. In the current study, the protective effect of co-administration of Zn and Se on VPA-induced reproductive toxicity in male rats was evaluated. Forty-eight male rats were divided into 8 groups of six (n=6): Control group (treated with normal saline); VPA only (250, 500, 1,000 mg/kg) group; VPA (500 mg/kg) plus Zn (2 mg/kg) group; VPA (500 mg/kg) plus Se (1.5 mg/kg) group; VPA (500 mg/kg) plus a combination of Zn and Se group; and VPA+vitamin E (20 mg/kg) group. The Animals were sacrificed after 28 days of treatment and sperm analysis was taken. Also, evaluation of oxidative stress markers including malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH) and histopathological changes were done on testis tissue. Morphological changes and a significant decrease in motility and sperm count in rats treated with VPA were observed. Also, an increase in oxidative stress marker, including MDA and PC and a decrease in GSH level was evident in VPA group. Zn and Se administration was able to protect against sperm abnormality, ameliorate the histological change in testis tissue, and suppressed the increase in oxidative stress markers induced by VPA. These results indicated that combination therapy with Zn and Se showed better an ameliorative effect than each one alone. Therefore, it can be suggested as an effective supplement for reproductive impairment in VPA-treated patient.

Zinc and selenium supplement mitigated valproic acid-induced testis toxicity by modulating the oxidative redox balance in male rats / 대한해부학회지

Valproic acid (VPA) is widely used antiepileptic agent which is associated with reproductive toxicity via impairment in oxidative redox. Zinc (Zn) and selenium (Se) are trace element with antioxidant effect that known to be essential for spermatogenesis. In the current study, the protective effect of co-administration of Zn and Se on VPA-induced reproductive toxicity in male rats was evaluated. Forty-eight male rats were divided into 8 groups of six (n=6): Control group (treated with normal saline); VPA only (250, 500, 1,000 mg/kg) group; VPA (500 mg/kg) plus Zn (2 mg/kg) group; VPA (500 mg/kg) plus Se (1.5 mg/kg) group; VPA (500 mg/kg) plus a combination of Zn and Se group; and VPA+vitamin E (20 mg/kg) group. The Animals were sacrificed after 28 days of treatment and sperm analysis was taken. Also, evaluation of oxidative stress markers including malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH) and histopathological changes were done on testis tissue. Morphological changes and a significant decrease in motility and sperm count in rats treated with VPA were observed. Also, an increase in oxidative stress marker, including MDA and PC and a decrease in GSH level was evident in VPA group. Zn and Se administration was able to protect against sperm abnormality, ameliorate the histological change in testis tissue, and suppressed the increase in oxidative stress markers induced by VPA. These results indicated that combination therapy with Zn and Se showed better an ameliorative effect than each one alone. Therefore, it can be suggested as an effective supplement for reproductive impairment in VPA-treated patient.

Study of antidepressant and sedative-hypnotic activity of hydroalcoholic extract of Asperugo procumbens L. aerial parts in mice

Asperugo procumbents L. has been used in Iranian traditional medicine for the refreshing, tranquillizing and mood elevating activities. The present study was undertaken to evaluate the antidepressant and sedative-hypnotic potential of acute administration of the hydroalcoholic extract of this plant in mice. Additionally, the effects of flumazenil on the hypnotic activity of the extracts were evaluated. None of the doses of the extract could significantly reduce immobility time in comparison with control group in antidepressant tests. In hypnotic test, 250 and 400 mg/kg doses significantly increased pentobarbital-induced sleeping time compared to vehicle. All of the doses of the extract significantly reduced the latency to sleep in comparison to the vehicle. Flumazenil reversed the augmented effects of extracts in pentobarbital-induced hypnotic test. The results of the present study indicate the low antidepressant and good sedative-hypnotic effects of the hydroalcoholic extract of Asperugo procumbens aerial parts in mice. Central benzodiazepine receptors are involved in the sedative-hypnotic effects of this plant

Design, synthesis and pharmacological evaluation of novel 2-[2-[2-chlorophenoxy] phenyl]-1,3,4-oxadiazole derivatives as benzodiazepine receptor agonists

New derivatives of 2-[2-[2-Chlorophenoxy]phenyl]-1,3,4-oxadiazole as candidates for agonistic effect on benzodiazepine receptors were synthesized. Conformational analysis and superimposition of energy minima conformers of the novel compounds on estazolam, a known benzodiazepine agonist, revealed that the main proposed benzodiazepine pharmacophores were well matched. In pharmacological evaluation, anticonvulsant activity of the compounds determined by pentylenetetrazole-induced lethal convulsion and maximal electroshock tests. The results showed that the introduction of an amino substituent in position 5 of 1,3,4- oxadiazole ring generates compound 6 that has a considerable effect. Compound 8 with a hydroxyl substituent on position 5 of 1,3,4- oxadiazole ring showed a relatively mild anticonvulsant activity, which was significantly weaker than that of diazepam and compound 6. Anticonvulsant effects of active compounds were antagonized by flumazenil, an antagonist of benzodiazepine receptors, indicating the involvement of benzodiazepine receptors in these effects.