Effects of Allopurinol as a xanthine oxidase inhibitor on depressive-like behavior of rats and changes in serum BDNF level.

Background: Depression is a psychiatric disorder characterized by low mood and loss of interest in daily activities. Allopurinol, a xanthine oxidase blocker, is widely administered for the treatment of hyperuricemia. Recently, its effects on serotonin and depressive like behaviors have been reported. On the other hand, the level of brain-derived neurotrophic factor (BDNF), a protective and regenerative neurotrophic, has been increased by many antidepressants. The purpose of this study was to evaluate the antidepressant effects of allopurinol and changes in serum level of BDNF compared to those of fluoxetine. Methods: Thirty-five male Wistar albino rats divided into five groups (control, 10 mg/kg fluoxetine, 25, 50 and 100 mg/kg allopurinol; n = 7 per group), that received all treatments intraperitoneally, every day. Forced swimming tests (FST), tail suspension test (TST) and open field test (OFT) were performed after 21 days of drug administration. Finally, the serum BDNF levels were measured using the sandwich ELISA method. Results: All doses of allopurinol and fluoxetine reduced the duration of immobility time in FST and TST. No significant changes were observed in the number of lines crossed in OFT between either allopurinol or fluoxetine groups and control group. Serum level of BDNF were significantly higher in fluoxetine and allopurinol 50 and 100 mg/kg groups. Conclusions: Long-term administration of allopurinol 50 and 100 mg/kg have shown antidepressant effects in behavioral tests along with an increase in the amount of serum BDNF concentration. The OFT results suggested that allopurinol did not have any significant effects on motor activity. The increased serum level of the BDNF in the allopurinol group was correlated with FST and TST results. However, it is still not clear whether the antidepressant effects of allopurinol are due to a direct effects on serotonin and/or BDNF or an indirect effect related to its xanthin oxidase inhibition.

Pyrrolopyridine and Isoindole as Potential Anticonvulsant Agents: Design, Synthesis, and Pharmacological Evaluation.

BACKGROUND AND OBJECTIVE: Phthalimide, as the rigid form of ameltolide, exhibits a phenytoin-like profile of drug-receptor interaction and is active in the MES model and inactive in the PTZ model as an anti-epileptic agent. In this research, based on the isosteric replacement, we reported the design, preparation, and antiepileptic activity of 13 new analogs of pyrrolopyridine and isoindole. METHODS: The designed compounds were prepared by condensing 3, 4-pyridine dicarboxylic anhydride, or 4-fluorophthalic anhydride with different aryl amines. MES and PTZ-induced seizure models were utilized to evaluate the antiepileptic effect of the prepared ligands. RESULTS: It was found that the prepared ligands have significantly affected both tonic and clonic seizures. In tonic seizures, the prepared compounds decreased mortality to a significant extent, and in clonic seizures, they significantly showed better frequency and latency. Compounds 9, 12, and 13 were the most potent ligands than phenytoin. CONCLUSION: It is concluded that the best distance between two aryl parts is two bonds, and the substitution of the nitro group at the meta position of the phenyl ring is better than the para position. Our research group has investigated this concept for designing newer compounds with better anticonvulsant activity.

Multi-organ system involvement in coronavirus disease 2019 (COVID-19): A mega review.

Since the pandemic of the coronavirus disease 2019 (COVID-19) infection, many people have been affected in different ways. The majority of infected people experience mild to moderate symptoms and recover without the need for hospitalization. However, in some affected people, it may lead to catastrophic disease. The severity of COVID-19 infection is widely influenced by co-morbidities, immune system functions, and extra-pulmonary organ injuries. Since the emergence of COVID-19, multi-organ involvement has been documented. In order to implement preventative and protective measures, full attention to potential organ injuries is required. Most existing articles and review papers are focused on a specific organ system, and their numbers are growing. In this review paper, attempts were made to collect review papers and articles published on seven organ system involvements in COVID-19 infection published till 15 July and highlight conclusions and managements of all affected organs. We tried to add to the medical knowledge on COVID-19, pointing out its multi-organ system impact. Finally, we tried to facilitate access to organized information and optimum conclusion by representing review tables for each organ system. Besides, this review article can clarify and magnify the empty research space easily for future investigations.

Protective Effects of Berberis vulgaris on Diazinon-Induced Brain Damage in Young Male Mice.

Diazinon is an imminent and hazardous chemical organophosphate multiplex that is generally used as a pesticide but is toxic for many species particularly vertebrates. Berberry (Berberis vulgaris L., family Berberidaceae) is a plant that flourishes in Europe and Asia that has been largely investigated for its therapeutic effects. In the present study, we evaluated the protective effects of B. vulgaris on diazinon-induced brain damage in young male mice. Twenty-one young male albino mice weighing 18±2 g were divided in three equal groups of seven mice, and treated orally with either olive oil (control), diazinon 50 mg/kg+B. vulgaris extract 200 mg/kg, or diazinon 50 mg/kg. After three weeks, cerebrum and cerebellum samples were collected for antioxidant assays. The results indicated that diazinon increased oxidative stress in the brain of mice. The glutathione content and proceedings of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase, and catalase, were significantly reduced in both the cerebellum and cerebrum of diazinon-treated mice, compared with the control group. In addition, acetylcholinesterase (AChE) activity was inhibited by exposure to this pesticide. Administration of 200 mg/kg B. vulgaris extract with diazinon significantly decreased oxidative stress indices in all experiments. The results indicated that B. vulgaris extract has protective effects against lipid peroxidation of the cerebellum and cerebrum, and in regenerating AChE activity in the brain induced by diazinon.

Effects of blackberry (Morus nigra) fruit juice on levodopa-induced dyskinesia in a mice model of Parkinson's disease.

BACKGROUND AND OBJECTIVE: Levodopa-induced dyskinesia (LID) is a movement disorder that occurs due to levodopa consumption for a long period to attenuate Parkinsonism. Plants have been the basis for medical treatments in human history and still widely practiced. Blackberry (Morus nigra) is one of the fruits rich in anthocyanin. The present study examined the effect of blackberry fruit juice on LID in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease in mice. MATERIALS AND METHODS: In this study, 42 male mice were used, which were divided into six groups equally: one control group and five groups receiving MPTP injection. After confirmation of Parkinsonism in MPTP groups, one group was preserved without treatment and four other groups were treated with levodopa (50 mg/kg ip). After the onset of LID (2 weeks), one group was kept without additional treatment and three other groups were treated with three different doses of blackberry fruit juice (5, 10, and 15 mL/kg) with levodopa orally for 7 days. Abnormal involuntary movement scale (AIMS) and cylinder behavioral test were carried out according to the schedule. The collected data were analyzed using the SPSS software with the significant level of P<0.05. RESULTS: Parkinson's disease was confirmed with AIMS test on the fourth day after MPTP injection. The onset of LID was observed after 2 weeks of levodopa treatment using both behavioral tests. The result of administration of M. nigra fruit juice for 1 week showed that this addition is useful in hindering LID. These effects were more pronounced at doses 10 and 15 mL/kg with nearly the same results on attenuating AIMS. Low dose of the fruit juice does not seem to affect LID significantly. CONCLUSION: M. nigra fruit juice is effective to attenuate LID in an MPTP-induced Parkinson mice model.

The effect of chronic administration of methylphenidate on morphometric parameters of testes and fertility in male mice.

BACKGROUND: Due to common use of methylphenidate (MPH) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and the role of the reproductive system in the production of gametes, studying the effects of this medication on the morphometry of testes, serum testosterone concentration, leydig cells function, and fertility rate was the aim of this study. METHODS: Twenty seven male mice (Balb/C), eight weeks old, were randomly divided into one control and two treated groups. After weighing the mice, the treated groups received MPH (produced in Novartis company) at the doses of 2 mg/kg and 10 mg/kg for 40 days. The control group received only normal saline. Subsequently, after weighing the animals, the weights of testes, dimensions of the testis, and the serum testosterone concentration were measured in six mice belonging to each group. After tissue processing, the samples were stained with hematoxylin and eosin, then the leydig cells were counted. In order to assess male fertility in each group, 3 male mice were chosen and each of them was kept with three female mice in a separate cage. After 10 days, the fertility rates of the male mice were determined by counting the number of embryos in uterus and the corpora lutea in their ovaries. RESULTS: The results of this study revealed that prescription of different doses of MPH can cause a significant decrease of the body weight. It reduces the number of leydig cells, too (p<0.01). Moreover, serum testosterone concentration (67.72±8.24 ng/ml in control group and 0.302±0.416 ng/ml after treatment with 2 mg/kg/day MPH) and fertility rate (95.42%±4.68% in control group and 64.96%±18.51% after treatment with 2 mg/kg/day MPH) of the male mice declined significantly in the treated groups compared with the control group (p<0.01), but it did not cause any changes in the weight or morphometric parameters of testes. CONCLUSION: The results of this study confirmed that MPH can negatively affect serum testosterone concentration and fertility rate of the male mice by decreasing the number of leydig cells and reducing the body weight.