1. Hepatic alterations in a BTBR T + Itpr3tf/J mouse model of autism and improvement using melatonin via mitigation oxidative stress, inflammation and ferroptosisRita Rezzani, Marzia Gianò, Daniela Pinto, Fabio Rinaldi, Cornelis J. F. van Noorden, Gaia Favero, 2024, original scientific article Abstract: Autism spectrum disorder (ASD) is a complicated neurodevelopmental disorder, and its etiology is not well understood. It is known that genetic and nongenetic factors determine alterations in several organs, such as the liver, in individuals with this disorder. The aims of the present study were to analyze morphological and biological alterations in the liver of an autistic mouse model, BTBR T + Itpr3tf/J (BTBR) mice, and to identify therapeutic strategies for alleviating hepatic impairments using melatonin administration. We studied hepatic cytoarchitecture, oxidative stress, inflammation and ferroptosis in BTBR mice and used C57BL6/J mice as healthy control subjects. The mice were divided into four groups and then treated and not treated with melatonin, respectively. BTBR mice showed (a) a retarded development of livers and (b) iron accumulation and elevated oxidative stress and inflammation. We demonstrated that the expression of ferroptosis markers, the transcription factor nuclear factor erythroid-related factor 2 (NFR2), was upregulated, and the Kelch-like ECH-associated protein 1 (KEAP1) was downregulated in BTBR mice. Then, we evaluated the effects of melatonin on the hepatic alterations of BTBR mice; melatonin has a positive effect on liver cytoarchitecture and metabolic functions.
Keywords: autism spectrum disorder, liver, oxidative stress, inflammation, ferroptosis
Published in DiRROS: 07.08.2024; Views: 100; Downloads: 90
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2. Functional responses in a lizard along a 3.5-km altitudinal gradientNina Guerra Serén, Rodrigo Megía-Palma, Tatjana Simčič, Miha Krofel, Fabio Maria Guarino, Catarina Pinho, Anamarija Žagar, Miguel A. Carretero, 2023, original scientific article Abstract: Aim: Physiological and metabolic performance are key mediators of the functional response of species to environmental change. Few environments offer such a multifaceted array of stressors as high-altitude habitats, which differ markedly in temperature, water availability, UV radiation and oxygen pressure compared to low-altitude habitats. Species that inhabit large altitudinal gradients are thus excellent models to study how organisms respond to environmental variation. Location: Tenerife island, Canary Islands archipelago (Spain). Taxon: Tenerife lizard (Gallotia galloti, Lacertidae). Methods: We integrated data on age structure, thermal and hydric regulatory behaviour and four metabolic and stress-related biomarkers for an insular lizard that inhabits an extreme altitudinal range (sea level to 3700 m a.s.l.), to understand how an ectotherms' age, ecophysiology and metabolism can be affected by extreme environmental variation. Results: We found marked differences in metabolic stress markers associated with altitude (particularly in the abundance of carbonyl metabolites and relative telomere length), but without a linear pattern along the altitudinal cline. Contrary to expectations, longer telomeres and lower carbonyl content were detected at the highest altitude, suggesting reduced stress in these populations. Evaporative water loss differed between populations but did not follow a linear altitudinal gradient. Lizard age structure or thermal physiological performance did not markedly change across different altitudes. Mixed signals in life-history and thermal ecology across populations and altitude suggest complex responses to variable conditions across altitude in this species. Main Conclusions: Our integrative study of multiple functional traits demonstrated that adaptation to highly divergent environmental conditions in this lizard is potentially linked to an interplay between plasticity and local adaptation variably associated with different functional traits.
Keywords: ecophysiology, evaporative water loss, metabolic activity, oxidative stress, preferred temperatures, relative telomere length, skeletochronology, lizard
Published in DiRROS: 12.07.2024; Views: 128; Downloads: 189
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3. Combined toxic effects of BPA and its two analogues BPAP and BPC in a 3D HepG2 cell modelMartina Štampar, Tim Ravnjak, Ana-Marija Domijan, Bojana Žegura, 2023, original scientific article Abstract: Bisphenol A (BPA) is one of the most commonly used substances in the manufacture ofvarious everyday products. Growing concerns about its hazardous properties, including endocrinedisruption and genotoxicity, have led to its gradual replacement by presumably safer analogues inmanufacturing plastics. The widespread use of BPA and, more recently, its analogues has increasedtheir residues in the environment. However, our knowledge of their toxicological profiles is limitedand their combined effects are unknown. In the present study, we investigated the toxic effectscaused by single bisphenols and by the combined exposure of BPA and its two analogues, BPAP andBPC, after short (24-h) and prolonged (96-h) exposure in HepG2 spheroids. The results showed thatBPA did not reduce cell viability in HepG2 spheroids after 24-h exposure. In contrast, BPAP andBPC affected cell viability in HepG2 spheroids. Both binary mixtures (BPA/BPAP and BPA/BPC)decreased cell viability in a dose-dependent manner, but the significant difference was only observedfor the combination of BPA/BPC (both at 40μM). After 96-h exposure, none of the BPs studiedaffected cell viability in HepG2 spheroids. Only the combination of BPA/BPAP decreased cellviability in a dose-dependent manner that was significant for the combination of 4μM BPA and 4μMBPAP. None of the BPs and their binary mixtures studied affected the surface area and growth ofspheroids as measured by planimetry. In addition, all BPs and their binary mixtures studied triggeredoxidative stress, as measured by the production of reactive oxygen species and malondialdehyde,at both exposure times. Overall, the results suggest that it is important to study the effects of BPsas single compounds. It is even more important to study the effects of combined exposures, as thecombined effects may differ from those induced by single compounds.
Keywords: BP analogues, hepatic in vitro 3D cell model, combined exposure, viability, oxidative stress, toxicology
Published in DiRROS: 12.07.2024; Views: 492; Downloads: 136
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4. Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm - an association of GPX1 polymorphism and recurrent Hurthle cell thyroid carcinomaBlaž Krhin, Katja Goričar, Barbara Gazić, Vita Dolžan, Nikola Bešić, 2016, original scientific article Abstract: Hurthle cells of the thyroid gland are very rich in mitochondria and oxidative enzymes. As a high level oxidative metabolism may lead to higher level of oxidative stress and can be associated with an increased risk for cancer, we investigated whether common functional polymorphisms in antioxidant genes (SOD2, CAT, GPX, GSTP1, GSTM1 and GSTT1) are associated with the development or clinical course of Hurthle cell thyroid carcinoma (HCTC). Methods. A retrospective study was performed in 139 patients treated by thyroid surgery for a Hurthle cell neoplasm. HCTC, Hurthle cell thyroid adenoma (HCTA) or Hurthle cell thyroid nodule (HCTN) were diagnosed by pathomorphology. DNA was extracted from cores of histologically confirmed normal tissue obtained from formalin-fixed paraffinembedded specimens and genotyped for investigated polymorphisms. Logistic regression was used to compare genotype distributions between patient groups. Results. HCTC, HCTA and HCTN were diagnosed in 53, 47 and 21 patients, respectively. Metastatic disease and recurrence of HCTC were diagnosed in 20 and 16 HCTC patients, respectively. Genotypes and allele frequencies of investigated polymorphisms did not deviate from Hardy-Weinberg equilibrium in patients with HCTC, HCTA and HCTN. Under the dominant genetic model we observed no differences in the genotype frequency distribution of the investigated polymorphisms when the HCTA and HCTN group was compared to the HCTC group for diagnosis of HCTC or for the presence of metastatic disease. However, GPX1 polymorphism was associated with the occurrence of recurrent disease (p = 0.040). Conclusions. GPX1 polymorphism may influence the risk for recurrent disease in HCTC.
Keywords: Hurthle cell thyroid carcinoma, Hurthle cell neoplasm, thyroid, oxidative stress
Published in DiRROS: 30.04.2024; Views: 380; Downloads: 102
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5. Systemic and airway oxidative stress in competitive swimmersSabina Škrgat, Peter Korošec, Izidor Kern, Mira Šilar, Julij Šelb, Matjaž Fležar, Robert Marčun, 2018, original scientific article Abstract: Background: The environment in swimming pools, which contain chlorine, might interact with the airway epithelium, resulting in oxidative stress and/or inflammation during high intensity training periods. Methods: We evaluated pulmonary functional (metacholine challenge test, FEV1 and VC), cellular (eosinophils and neutrophils), inflammatory (FeNo, IL-5, IL-6, IL-8 and TNF-[alpha]), oxidative (8-isoprostanes) and angiogenesis factors (VEGF) in induced sputum and peripheral blood of 41 healthy non-asthmatic elite swimmers (median 16 years) during the period of high intensity training before a national championship. The second paired sampling was performed seven months later after training had been stopped for one month. Results: There was a ten-fold increase (median 82-924 pg/ml; P < 0.001) in 8-isoprostanes in induced sputum and five-fold increase (median 82-924 pg/ml; P < 0.001) in sera during training in comparison to the period of rest. However, there was no difference in FEV1 (113 vs 116%), VC (119 vs 118%), FeNo (median 34 vs 38 ppb), eosinophils (2.7 vs 2.9% in sputum; 180 vs 165 cells/[micro]l in blood), neutrophils, different cytokines or VEGF in induced sputum or sera. The only exception was TNF-[alpha], which was moderately increased in sera (median 23 vs 40 pg/ml; P=0.02) during the peak training period. Almost half (18 of 41) of swimmers showed bronchial hyperresponsiveness during the peak training period (PC20 cutoff was 4 mg/ml). There was no correlation between hyperresponsiveness and the markers of oxidative stress or inflammation. Conclusions: High intensity training in healthy, non-asthmatic competitive swimmers results in marked oxidative stress at the airway and systemic levels, but does not lead to airway inflammation. However, we could not confirm that oxidative stress is associated with bronchial hyperresponsiveness (AHR), which is often observed during the peak exercise training period.
Keywords: bronchial diseases, swimming, oxidative stress, bronchial hyperresponsiveness, competitive swimmers, training
Published in DiRROS: 23.11.2020; Views: 1918; Downloads: 531
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