Polish Journal of Pharmacology 

About: Polish Journal of Pharmacology is an academic journal. The journal publishes majorly in the area(s): Agonist & Receptor. Over the lifetime, 868 publications have been published receiving 13952 citations.

Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study.

Abstract: A growing body of evidence implicates a derangement of zinc homeostasis in mood disorders. In general, unipolar depression is connected with low blood zinc levels that are increased by effective antidepressant therapy. A placebo-controlled, double blind pilot study of zinc supplementation in antidepressant therapy was conducted in patients who fulfilled DSM IV criteria for major (unipolar) depression. Patients received zinc supplementation (6 patients; 25 mg of Zn2+ once daily) or placebo (8 patients) and were treated with standard antidepressant therapy (tricyclic antidepressants, selective serotonin reuptake inhibitors). Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) were used to assess efficacy of antidepressant therapy, and patients' status was evaluated before the treatment and 2, 6 and 12 weeks after its commencement. Antidepressant treatment significantly reduced HDRS scores by the 2nd week of treatment in both groups, and lowered BDI scores at the 6th week in zinc-treated group. Zinc supplementation significantly reduced scores in both measures after 6- and 12-week supplementation when compared with placebo treatment. This preliminary study is the first demonstration of the benefit of zinc supplementation in antidepressant therapy. The mechanism(s) may be related to modulation of glutamatergic or immune systems by zinc ion.

Bioactivity of flavonoids.

Abstract: Flavonoids are benzo-gamma-pyrone derivatives of plant origin. They possess wide spectrum of biological activity. From the therapeutical point of view the most important are their antioxidant properties. These are the result of high propensity to electron transfer, ferrous ions chelating activity and direct scavenging of reactive oxygen species. Flavonoids inhibit enormous number of enzymes. From the pharmacological point of view inhibition of cyclooxygenase and lipoxygenases as well as scavenging of superoxide anions seem to be essential. Flavonoids are antiinflammatory agents as the result of diminished formation of proinflammatory mediators (prostaglandins, leukotrienes, reactive oxygen species, nitric oxide). They are also antithrombotic owing to their ability to scavenge superoxide anions. These anions are strong inhibitors of prostacyclin production. Removal of superoxide anions by flavonoids facilitates antiaggregatory PGI2 formation. Superoxide anions generate proagregatory isoprostanes. The antiaggregatory effect of flavonoids may be due to the limitation of formation of isoprostanes. Empirical use of flavonoids as drugs acquired recently scientific confirmation.

Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage.

Abstract: This review briefly summarizes the actions of melatonin in reducing molecular damage caused by free radicals and associated oxygen- and nitrogen-based reactants. All the mechanisms by which melatonin is protective of such a wide variety of molecules, i.e. lipids, proteins, DNA, etc., and in such widely diverse areas of the cell and different organs are likely not yet all identified. Melatonin actions that have been identified include its ability to directly neutralize a number of toxic reactants and stimulate antioxidative enzymes. Furthermore, several metabolites that are formed when melatonin neutralizes damaging reactants are themselves scavengers suggesting that there is a cascade of reactions that greatly increase the efficacy of melatonin in styming oxidative mutilation. Suggested, but less well defined, processes which may contribute to melatonin's ability to reduce oxidative stress include stimulation of glutathione synthesis (an important antioxidant which is at high concentrations within cells), reducing electron leakage from the mitochondrial electron transport chain (which would reduce free radical generation), limiting cytokine production and inflammatory processes (actions that would also lower toxic reactant generation), and synergistic effects with other classical antioxidants (e.g. vitamins C, E and glutathione). Clearly which of these multiple mechanisms contribute to melatonin's high efficacy in curtailing oxidative damage remains to be clarified. Likewise, it is possible that the key action of melatonin in reducing molecular damage induced by oxygen and nitrogen-based metabolites remains to be identified. Finally, the review summarizes some of the large amount of data documenting the ability of melatonin to limit molecular and organ damage in two situations, i.e. ischemia-reperfusion and ionizing radiation, where free radicals are generally conceded as being responsible for much of the resulting tissue destruction.

Adrenomedullin--what do we know 10 years since its discovery?

Abstract: Adrenomedullin (ADM) is a 52-amino acid peptide with structural homology to calcitonin gene-related peptide (CGRP) initially isolated from human pheochromocytoma. ADM is synthesized by many mammalian tissues including the adrenal medulla, endothelial and vascular smooth muscle cells, myocardium and central nervous system. ADM binds to plasma membrane receptors composed of calcitonin receptor-like receptor (CRLR), a member of serpentine receptor superfamily, and receptor activity modifying protein (RAMP) type 2 or 3. ADM has also some affinity for CGR(1) receptor composed of CRLR and RAMP1. ADM dilates blood vessels in both endothelium-dependent and independent manner and decreases systemic arterial pressure. Intrarenally administered ADM increases natriuresis by vascular and tubular mechanisms. In addition, ADM inhibits migration and proliferation of vascular smooth muscle cells and attenuates myocardial remodelling by inhibiting protein synthesis in cardiomyocytes and proliferation of cardiac fibroblasts. ADM is expressed in various tissues from early stage of embryogenesis and is also synthesized in placenta, uterus and fetal membranes. Plasma ADM level is increased in arterial hypertension, acute coronary syndromes, heart failure, renal diseases and septic shock, being involved in the pathophysiology of these disorders. Experimental ADM treatment is beneficial in arterial and pulmonary hypertension, heart failure, septic shock and ischemia/reperfusion injury. Proadrenomedullin N-terminal peptide (PAMP) is another product of ADM gene which is co-secreted by ADM-producing tissues, with some effects similar and some opposite to ADM.

Neuroprotective role of testosterone in the nervous system.

Abstract: Testosterone -- the gonadal sex steroid hormone plays an important role in the central nervous system (CNS) development. One of the less known testosterone actions is neuroprotection. There are some evidences supporting the hypothesis that testosterone may act protectively in neurodegenerative disorders, e.g. Alzheimer's disease (AD), mild cognitive impairment (MCI) or depression. Androgens alter also the morphology, survival and axonal regeneration of motor neurons. These hormones accelerate the regeneration of hamster facial nerve and anterior tibialis sciatic nerve in rabbits following crush axotomy. Androgens exert trophic action in laryngeal motor nucleus of Xenopus laevis. Testosterone is linked to an increase in neuron somal size, neuritic growth, plasticity and synaptogenesis in both motoneurons of the spinal nucleus of the bulbocavernosus and several populations of pelvic autonomic neurons. The hormone reduced the extent of spinal cord damage in vitro. There are also evidences against the neuroprotective action of testosterone. Testosterone does not protect against methamphetamine-induced neurotoxicity of the dopaminergic system in mice and does not provide significant neuroprotection against glutamate-induced neurotoxicity. Androgens do not prevent striatal dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Although the role of testosterone in the CNS is still poorly understood, accumulating evidence suggests that testosterone may create a future treatment for MCI and related cognitive diseases, including dementia and may influence motor neuron regeneration in adulthood. Androgen replacement therapy in selected male populations may hold therapeutic promise for the prevention and/or treatment of age-related disorders associated with neuronal injury.