Rho kinase inhibition ameliorates cyclophosphamide-induced cystitis in rats

Naunyn-Schmiedeberg's Archives of Pharmacology - Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CYP). Studies have indicated that Rho kinase (ROCK) inhibitors...     

Time course of zinc deprivation-induced alterations of mice behavior in the forced swim test

BackgroundZinc is an important trace element essential for numerous bodily functions. It is believed that a deficiency of zinc can lead to various conditions, including depression, on which this study is focused. It is still not known if hypozincemia leads to the development of depression or whether zinc deficiency is a result of depression. It is hypothesized that zinc may be a therapeutic agent or supplement that would help to reverse the symptoms of this disease.MethodsIn the present study, the behavior of mice was assessed 2, 4, and 10 weeks following administration of a zinc deficient diet. To evaluate animal activity we used the forced swim test (FST).ResultsAfter 2-week zinc deprivation we demonstrated a significant reduction in the immobility time. However, after 4 and 10 weeks of zinc deprivation the mice exhibited an increased immobility time. There were no changes in locomotor activity at each time period. After 2-, 4- and 10-week zinc deprivation and the subsequent FST, serum zinc concentration was decreased and determined to be 59, 61 and 20%, respectively, compared with appropriate controls. The serum corticosterone concentration in mice after 2-, 4-and 10-week zinc deprivation and subjected to the FST was also assessed, whereby the differences between the control and experimental animals were demonstrated (increased by: 11, 97 and 225%, respectively).ConclusionsThe obtained results indicate that zinc deprivation induced “pro-depressive” behavior (after the initial period of “anti-depressive” behavior). This pro-depressive behavior correlates with enhanced serum corticosterone concentration.     

Zinc deficiency alters responsiveness to antidepressant drugs in mice

BackgroundThere is some evidence coming from preclinical and clinical studies suggesting a relationship between dietary zinc intake and depressive symptoms. The aim of the study was to determine whether zinc deficiency alters the response to antidepressants with a different mechanism of action.We examine also whether these changes are related to activity of the hypothalamic-pituitary-adrenal HPA axis.MethodsMale CD-1 mice were assigned to groups according to diet and antidepressant administration. To evaluate animal behavior, the immobility time in the forced swim test (FST) and locomotor activity were measured. To determine serum zinc levels the flame atomic absorption spectroscopy (FAAS) was used. The serum corticosterone was determined by radioimmunoassay (RIA).ResultsAntidepressants administered to zinc-deprived mice induced an altered response in the FST when compared to animals fed with an adequate diet. There were no changes in locomotor activity. Animals subjected to a zinc-deficient diet showed a significant reduction in serum zinc levels, which was normalized by antidepressant treatment. An increase in serum corticosterone concentrations in mice fed with a zinc-deficient diet and treated with antidepressants was observed, so it can be concluded that reduced levels of zinc contribute hyperactivation of the HPA axis.ConclusionThe results of this study suggest that a diet with a reduced zinc level alters antidepressant action, which is associated with a reduction in the serum zinc level and rise in the corticosterone level. The results of this study may indicate the involvement of zinc deficiency in the pathogenesis of depression.     

Anxiolytic-like activity of zinc in rodent tests

Because zinc deficiency induces depression and anxiety-like behavior in rodents, we examined the effects of zinc administration in several tests by measuring anxiolytic activity in mice and rats. We now report that zinc significantly increased the number of entries into the open arms in the elevated plus maze in rats. Moreover, zinc treatment significantly increased the number of punished crossings in the four-plate test and attenuated stress-induced hyperthermia (SIH) in mice. However, no effect of zinc administration was observed in the elevated plus maze test in mice. This lack of effect in the latter case was probably due to the substantial zinc-induced reduction in locomotor activity by the doses used in mice. The present data demonstrate for the first time the anxiolytic-like activity of zinc in rodents and may indicate that zinc could be used as a novel therapeutic/adjunct agent in anxiolytic therapy.     

Effect of Tadalafil on Seizure Threshold and Activity of Antiepileptic Drugs in Three Acute Seizure Tests in Mice

Tadalafil, a selective phosphodiesterase type 5 inhibitor, is a long-acting oral agent for the treatment of erectile dysfunction of multiple etiologies. Although generalized tonic-clonic seizures were reported in a healthy man after taking tadalafil, the influence of tadalafil on seizure susceptibility has not been studied so far. Therefore, the aim of the present study was to investigate the effect of tadalafil on seizure threshold as well as on the activity of some first- and second-generation antiepileptic drugs in three acute seizure tests in mice. The obtained results showed that tadalafil, at the highest dose tested (20 mg/kg), significantly decreased the threshold for the first myoclonic twitch in the intravenous pentylenetetrazole (i.v. PTZ) seizure test. It did not affect the threshold for generalized clonic seizure and forelimb tonus in the i.v. PTZ, for tonic hindlimb extension in the maximal electroshock seizure threshold test, and for psychomotor seizure in the 6-Hz-induced seizure threshold test. Tadalafil did not alter the anticonvulsant activity of any of the studied antiepileptic drugs in electrically induced seizure tests. Interestingly, tadalafil potentiated the anticonvulsant activity of clonazepam and decreased the anticonvulsant activity of oxcarbazepine in the i.v. PTZ test. These interactions were pharmacodynamic in nature, as tadalafil did not alter clonazepam and oxcarbazepine concentrations both in serum and brain tissue. Furthermore, neither tadalafil alone nor its combinations with the studied antiepileptic drugs produced any significant impairment of motor coordination (assessed in the chimney test), muscular strength (investigated in the grip-strength test), and long-term memory (assessed in the passive avoidance task). In conclusion, tadalafil may increase the risk of myoclonic seizure and decrease the anticonvulsant efficacy of oxcarbazepine. Further studies are warranted to evaluate the safety of tadalafil usage in patients with epilepsy.