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Highly active antiretroviral therapy (HAART) is used in HIV-infected patients. Alongside the prolongation of patients’ life, adverse side effects associated with long-term therapy are becoming an increasing problem. Therefore, optimizing of HAART is extremely important. The study is aimed at evaluating the toxicity of abacavir and etravirine in monotherapy on the reproductive system, liver, kidneys, and bones in young, sexually mature, male rats. Thirty-six 8-week-old male Wistar rats randomized into three 12-animal groups received either normal saline (control), abacavir 60 mg/kg (AB group), or etravirine 40 mg/kg (ET group) once daily for 16 weeks. Semen morphology, oxide–redox state parameters (MDA, SOD, catalase, GPx, glutathione, GSH/GSSG ratio) in tissue homogenates (testes, liver, kidneys), and serum samples were studied. In bones, microcomputed tomography and a four-point bending test were performed. Total sperm count, sperm concentration, motility, and sperm morphology did not differ significantly in AB or ET groups compared to the control. In the flow cytometry of semen, an increased percentage of cells with denatured DNA was noticed for both tested drugs. However, no significant changes of oxide–redox state in testicular homogenates were found, except of increased SOD activity in the AB-receiving group. Additionally, ET significantly altered catalase and GPx in the liver and SOD activity in kidneys. Abacavir decreased catalase in the liver and GSH levels in kidneys. AB caused significant changes to bone microarchitecture (bone volume fraction, trabecular number, connectivity density, total porosity) and increased Young’s modulus. Etravirine had a greater impact on macrometric parameters of bones (tibial index, mid-tibial diameter, femur length). After 4 weeks in the ET group, a lower 1,25-dihydroxyvitamin D3 serum concentration was found. The results showed that abacavir and etravirine disturb oxidative stress. An increase in the percentage of sperms with chromatin damage suggests decreased fertility in rats receiving the studied drugs. Both drugs affected bone formation in growing rats. Additionally, etravirine disturbed vitamin D metabolism.

et al. Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats. AbstractBackground. Fenspiride is an antagonist of H1-histamine receptors that is used to treat acute and chronic respiratory tract infections and otitis media in children and adolescents.Objectives. The aim of the study was to assess the influence of long-term administration of fenspiride on bone mineral density (BMD) and bone turnover in young growing rats.Material and methods. The experiment was carried out on 18 young (8-week-old) male Wistar rats receiving either fenspiride 15 mg/kg intragastrically (ig) (group F) or saline solution 4 mL/kg ig (group C) for 3 months. On days 1 and 93, blood samples were collected and serum levels of calcium, phosphorus and markers of bone turnover were measured. On days 2 and 92, BMD was measured with dual-energy X-ray absorptiometry (DXA) using small animal software. Results.We detected no influence of fenspiride on weight gain, total body BMD (0.212 ±0.010 g/cm 2 vs 0.204 ±0.024 g/cm 2 ), hind limb BMD (0.264 ±0.016 g/cm 2 vs 0.252 ±0.027 g/cm 2 ), or bone macroscopic parameters. There were no significant differences between group F and group C in serum levels of osteocalcin (group F: 0.42 ±0.09 ng/mL vs group C: 0.43 ±0.08 ng/mL), C-terminal telopeptide of type I collagen (F: 0.31 ±0.08 ng/mL vs C: 0.29 ±0.08 ng/mL), osteoprotegerin (F: 5.47 ±0.78 pg/mL vs C: 5.35 ±1.65 pg/mL), receptor activator of nuclear factor kappa B ligand (F: 0.65 ±0.85 pg/mL vs C: 0.56 ±0.86 pg/mL), parathormone (F: 237 ±182 pg/mL vs C: 289 ±200 pg/mL), total calcium (F: 6.38 ±1.50 mg/dL vs C: 6.83 ±1.71 mg/dL), or inorganic phosphorus (F: 5. 19 ±1.76 mg/dL vs C: 5.50 ±1.32 mg/dL). Conclusions.Long-term administration of fenspiride has no negative impact on BMD and bone metabolism in young growing rats.

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BackgroundIn young organisms intensive bone turnover is observed and it allows the skeleton to achieve proper side, shape and weight of bones. It is extremely important to assess the influence on various drugs on growing bones. Fenspiride is registered for therapy of acute and chronic respiratory tract infections in children and adolescence. It decreases the synthesis of proinflammatory cytokines, blocks H1 receptors and has bronchodilatotory properties.ObjectivesThe aim of the study was to assess the influence of long-term administration of fenspiride on bone mineral density and selected markers on bone turnover in young growing rats.MethodsThe experiment was carried out on18 young (8-week-old) male Wistar rats receiving standard diet containing 1.2% of calcium ans 0.7% of phosphate. Rats were randomly assigned to one of two groups (9 animals in each group): group F – rats receiving fespiride (15 mg /kg) in saline solution (4ml/kg), and group C (control group) - rats receiving saline solution (4ml/kg). Saline solution and fenspiride were given intragastrically once daily for 90 days (from day 3 to day 92). On day 1 and 93 blood samples for serum isolation were collected. Markers of bone turnover were assessed with commercial ELISA kits according to producers' instruction. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) with Hologic DXA equipment (Hologic Dicovery W 81507) using a small animal software. The experiment was performed with the approval of the First Local Ethics Committee for Experiments on Animals in Wroclaw.ResultsOn Day 1 there was no difference in age and body weight between groups. On Day 1 no difference in total body bone mineral density (BMD) (0.160±0.0065 g/cm2 vs. 0.1608±0.0056 g/cm2), lower limbs BMD (0.232±0.0267 g/cm2 vs. 0.2274±0.0314 g/cm2), serum levels of bone turnover markers (osteocalcin: 1000.921±109.0705 pg/ml vs. 952.5777±178.5306 pg/ml; bCTX: 280.089±54.4298 pg/ml vs. 292.8979±116.0042 pg/ml; osteoprotegerin: 3.5±0.6338 pg/ml vs. 3.7963±0.6894 pg/ml; RANKL: 0.167±0.4099 pg/ml vs. 1.0218±1.2717 pg/ml) was detected.On Day 93 there was no difference in body weight, total body BMD and lower limbs (0.212±0.0104 g/cm2 vs. 0.2035±0.0242 g/cm2; 0.264±0.0159 g/cm2 vs. 0.2520±0.0271 g/cm2, respectivelly) between groups. On Day 93 no difference between groups in serum bone turnover markes was detected (OC: 422.758±92.3316 pg/ml vs. 429.2071±83.0520 pg/ml; bCTX: 307.748±77.6733 pg/ml vs. 285.3486±79.16334; OPG: 5.466±0.7815 pg/ml vs. 5.3520±1.6458 pg/ml; RANKL:0.647±0.8457 pg/ml vs. 0.5630±0.8608 pg/ml).ConclusionsLong-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing ratsAcknowledgementsResearch was supported with Wroclaw Medical University Grant for Young Researchers Pbmn 138.Disclosure of InterestNone declared

Schizophrenia is a severe mental disorder with a chronic, progressive course. The etiology of this condition is linked to the interactions of multiple genes and environmental factors. The earlier age of onset of schizophrenia, the higher frequency of negative symptoms in the clinical presentation, and the poorer response to antipsychotic treatment in men compared to women suggests the involvement of sex hormones in these processes. This article aims to draw attention to the possible relationship between testosterone and some clinical features in male schizophrenic patients and discuss the complex nature of these phenomena based on data from the literature. PubMed, Web of Science, and Google Scholar databases were searched to select the papers without limiting the time of the publications. Hormone levels in the body are regulated by many organs and systems, and take place through the neuroendocrine, hormonal, neural, and metabolic pathways. Sex hormones play an important role in the development and function of the organism. Besides their impact on secondary sex characteristics, they influence brain development and function, mood, and cognition. In men with schizophrenia, altered testosterone levels were noted. In many cases, evidence from available single studies gave contradictory results. However, it seems that the testosterone level in men affected by schizophrenia may differ depending on the phase of the disease, types of clinical symptoms, and administered therapy. The etiology of testosterone level disturbances may be very complex. Besides the impact of the illness (schizophrenia), stress, and antipsychotic drug-induced hyperprolactinemia, testosterone levels may be influenced by, i.a., obesity, substances of abuse (e.g., ethanol), or liver damage.

Bone structure abnormalities are increasingly observed in patients chronically treated with antiepileptic drugs (AEDs). The majority of the available data concern older conventional AEDs, while the amount of information regarding newer AEDs, including stiripentol, is limited. The aim of the study was to assess the effect of stiripentol on bones. For 24 weeks, male Wistar rats, received 0.9% sodium chloride (control group) or stiripentol (200 mg/kg/day) (STP group). In the 16th week of the study, we detected lower serum PINP levels in the STP group compared to the control group. In the 24th week, a statistically significant lower 1,25-dihydroxyvitamin D3 level, higher inorganic phosphate level and higher neutrophil gelatinase-associated lipocalin (NGAL) levels in serum were found in the STP group compared to the control. Micro X-ray computed tomography of the tibias demonstrated lower bone volume fraction, lower trabecular thickness, higher trabecular pattern factor and a higher structure model index in the stiripentol group. Considering the results of this experiment on rats which suggests that long-term administration of stiripentol may impair the cancellous bone microarchitecture, further prospective human studies seem to be justified. However, monitoring plasma vitamin D, calcium, inorganic phosphate and kidney function in patients on long-term stiripentol therapy may be suggested.