Gentamicin, belonging to the aminoglycosides, possesses the greatest nephrotoxic effect of all other antibiotics from this group. On the other hand, pioglitazone, which represents peroxisome proliferator-activated receptor γ (PPARγ) agonist recently showed antiinflamatory, antioxidative effects, amelioration of endothelial dysfunction etc. Therefore, the goal of our study was to investigate the effects of pioglitazone on kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats. These effects were observed by following values of biochemical (serum urea and creatinine) parametars, total histological kidney score, urine level of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) as well as parametars of oxidative stress (malondialdehyde, superoxide dismutase, catalase, total oxidant status, total antioxidant status, oxidative stress index and advanced oxidation protein products). It seems that pioglitazone protects the injured rat kidney in a U-shaped manner. Medium dose of pioglitazone (1 mg/kg, i.p.) was protective regarding biochemical (serum urea and creatinine), total histological score and the values of kidney injury molecule-1 (KIM-1) (P < 0.05 vs. control group, i.e. rats injected with gentamicin only). This finding could be of great importance for the wider use of aminoglycosides, with therapy that would reduce the occurrence of serious adverse effects, such as nephrotoxicity and acute renal failure.

The endothelium has a central role in the regulation of blood flow through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, or anticoagulant effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO) synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation. So far, the pharmacological approach in improving/reversal of endothelial dysfunction was shown to be beneficial in clinical trials that have investigated actions of different cardiovascular drugs. The aim of this paper was to summarize some of the latest clinical findings related to therapeutic possibilities for improving endothelial dysfunction in different pathological conditions. In the majority of presented clinical investigations, the assessment of improvement or reversal of endothelial dysfunction was performed through the flow-mediated dilatation measurement, and in some of those endothelial progenitor cells’ count was used for the same purpose. Still, given the fast and continuous development of this field, the evidence acquisition included the MEDLINE data base screening and the selection of articles published between 2010 and 2012.

: Lithium is the smallest monovalent cation with many different biological effects. Although lithium is present in the pharmacotherapy of psychiatric illnesses for decades, its precise mechanism of action is still not clarified. Today lithium represents first-line therapy for bipolar disorders (because it possesses both antimanic and antidepressant properties) and the adjunctive treatment for major depression (due to its antisuicidal effects). Beside, lithium showed some protective effects in neurological diseases including acute neural injury, chronic degenerative conditions, Alzheimer's disease as well as in treating leucopenia, hepatitis and some renal diseases. Recent evidence suggested that lithium also possesses some anticancer properties due to its inhibition of Glycogen Synthase Kinase 3 beta (GSK3β) which is included in the regulation of a lot of important cellular processes such as: glycogen metabolism, inflammation, immunomodulation, apoptosis, tissue injury, regeneration etc.: Although recent evidence suggested a potential utility of lithium in different conditions, its broader use in clinical practice still trails. The reason for this is a narrow therapeutic index of lithium, numerous toxic effects in various organ systems and some clinically relevant interactions with other drugs. Additionally, it is necessary to perform more preclinical as well as clinical studies in order to a precise therapeutic range of lithium, as well as its detailed mechanism of action. The aim of this review is to summarize the current knowledge concerning the pharmacological and toxicological effects of lithium.

The endothelium is one of the most important constituents of vascular homeostasis, which is achieved through continual and balanced production of different relaxing and contractile factors. When there is a pathological disturbance in release of these products, endothelial dysfunction (ED) will probably occur. ED is considered to be the initial step in the development of atherosclerosis. This pathological activation and inadequate functioning of endothelial cells was shown to be to some extent a reversible process, which all together resulted in increased interest in investigation of different beneficial treatment options. To this point, the pharmacological approach, including for example, the use of angiotensin-converting enzyme inhibitors or statins, was clearly shown to be effective in the improvement of ED. One of many critical issues underlying ED represents instability in the balance between nitric oxide and angiotensin II (Ang II) production. Considering that Ang II was confirmed to be important for the development of ED, the aim of this review article was to summarize the findings of up to date clinical studies associated with therapeutic application of angiotensin receptor blockers and improvement in ED. In addition, it was of interest to review the pleiotropic actions of angiotensin receptor blockers linked to the improvement of ED. The prospective, randomized, double-blind, placebo or active-controlled clinical trials were identified and selected for the final evaluation.