Marcelo Farina

Publications (104) View all

• Article: Sub-acute administration of (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate induces toxicity and oxidative stress in mice: unexpected effects of N-acetylcysteine.

  Daiane F Meinerz, Bruna Comparsi, Josiane Allebrandt, Douglas Oscar Ceolin Mariano, Danúbia B Dos Santos, Ana Paula Pegoraro Zemolin, Marcelo Farina, Luiz Alcir Dafre, João B T Rocha, Thaís Posser, Jeferson L Franco
  [show abstract] [hide abstract]
  ABSTRACT: The organic tellurium compound (S)-dimethyl 2-(3-(phenyltellanyl) propanamide) succinate (TeAsp) exhibits thiol-peroxidase activity that could potentially offer protection against oxidative stress. However, data from the literature show that tellurium is a toxic agent to rodents. In order to mitigate such toxicity, N-acetylcysteine (NAC) was administered in parallel with TeAsp during 10 days. Mice were separated into four groups receiving daily injections of (A) vehicle (PBS 2.5 ml/kg, i.p. and DMSO 1 ml/kg, s.c.), (B) NAC (100 mg/kg, i.p. and DMSO s.c.), (C) PBS i.p. and TeAsp (92.5 μmol/kg, s.c), or (D) NAC plus TeAsp. TeAsp treatment started on the fourth day. Vehicle or NAC-treated animals showed an increase in body weight whereas TeAsp caused a significant reduction. Contrary to expected, NAC co-administration potentiated the toxic effect of TeAsp, causing a decrease in body weight. Vehicle, NAC or TeAsp did not affect the exploratory and motor activity in the open-field test at the end of the treatment, while the combination of NAC and TeAsp produced a significant decrease in these parameters. No DNA damage or alterations in cell viability were observed in leukocytes of treated animals. Treatments produced no or minor effects on the activities of antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase, whereas the activity of the thioredoxin reductase was decreased in the brain and increased the liver of the animals in the groups receiving TeAsp or TeAsp plus NAC. In conclusion, the toxicity of TeAsp was potentiated by NAC and oxidative stress appears to play a central role in this process.
  SpringerPlus. 12/2013; 2(1):182.
• Article: Diphenyl diselenide modulates oxLDL-induced cytotoxicity in macrophage by improving the redox signaling.

  Marcos Raniel Straliotto, Mariana Appel Hort, Bianca Fiuza, João Batista Teixeira Rocha, Marcelo Farina, Gustavo Chiabrando, Andreza Fabro de Bem
  [show abstract] [hide abstract]
  ABSTRACT: It has been reported that oxidized LDLs (oxLDL) are involved in the pathogenesis of atherosclerosis, and that macrophages as well as other cells of the arterial wall can oxidize LDL in vitro, depending on the balance between intracellular prooxidant generation and antioxidant defense efficiency. Because of their potencial beneficial role in preventing atherosclerosis and other oxidative stress-related diseases, organoselenium compounds such as diphenyl diselenide (PhSe)2, are receiving increased attention. In the present work, we investigated the mechanisms underlying the protective effect exerted by (PhSe)2 on oxLDL-mediated effects in murine J774 macrophage-like cells. (PhSe)2 pretreatment reduced atherogenic signaling triggered by oxLDL in macrophages in vitro, namely: ROS generation, disturbance of (•)NO homeostasis, activation of matrix metalloproteinase, foam cell formation, and mitochondrial dysfunction. Moreover, the redox signaling effects of (PhSe)2 presented herein were accompanied by a downregulation of NF-κB-binding activity. The relatively strong performance of (PhSe)2 makes it an ideal candidate for further, expanded trials as a new generation of antioxidants for preventing atherosclerotic lesion.
  Biochimie 04/2013; · 3.02 Impact Factor
• Article: Platelet oxygen consumption as a peripheral blood marker of brain energetics in a mouse model of severe neurotoxicity.

  Roberta de Paula Martins, Viviane Glaser, Débora da Luz Scheffer, Priscila Maximiliana de Paula Ferreira, Clóvis Milton Duval Wannmacher, Marcelo Farina, Paulo Alexandre de Oliveira, Rui Daniel Prediger, Alexandra Latini
  [show abstract] [hide abstract]
  ABSTRACT: Interactions of chemicals with cerebral cellular systems are often accompanied by similar changes involving components in non-neural tissues. On this basis, indirect strategies have been developed to investigate neural cell function parameters by methods using accessible cells, including platelets and/or peripheral blood lymphocytes. Therefore, here it was investigated whether peripheral blood markers may be useful for assessing the central toxic effects of methylmercury (MeHg). For this purpose, we investigated platelet mitochondrial physiology in a well-established mouse model of MeHg-induced neurotoxicity, and correlated this peripheral activity with behavioural and central biochemical parameters. In order to characterize the cortical toxicity induced by MeHg (20 and 40 mg/L in drinking water, 21 days), the behavioral parameter namely, short-term object recognition, and the central mitochondrial impairment assessed by measuring respiratory complexes I-IV enzyme activities were determined in MeHg-poisoned animals. Neurotoxicity induced by MeHg exposure provoked compromised cortical activity (memory impairment) and reduced NADH dehydrogenase, complex II and II-III activities in the cerebral cortex. These alterations correlated with impaired systemic platelet oxygen consumption of intoxicated mice, which was characterized by reduced electron transfer activity and uncoupled mitochondria. The data brought here demonstrated that impaired systemic platelet oxygen consumption is a sensitive and non-invasive marker of the brain energy deficits induced by MeHg poisoning. Finally, brain and platelets biochemical alterations significantly correlated with cognitive behavior in poisoned mice. Therefore, it could be proposed the use of platelet oxygen consumption as a peripheral blood marker of brain function in a mouse model MeHg-induced neurotoxicity.
  Journal of Bioenergetics 03/2013; · 2.81 Impact Factor
• Article: Effects of lifestyle modifications on cognitive impairments in a mouse model of hypercholesterolemia.

  Eduardo Luiz Gasnhar Moreira, Aderbal S Aguiar Jr, Cristiane Ribeiro de Carvalho, Danúbia Bonfanti Santos, Jade de Oliveira, Andreza Fabro de Bem, João Carlos Xikota, Roger Walz, Marcelo Farina, Rui Daniel Prediger
  [show abstract] [hide abstract]
  ABSTRACT: Epidemiological studies indicate that high midlife plasma cholesterol levels increases the risk of Alzheimer's disease. Moreover, middle-aged familial hypercholesterolemia (FH) subjects show a particularly high incidence of mild cognitive impairments (MCI). These evidence points to hypercholesterolemia as one of the modifiable risk factors focused on prevention/treatment of cognitive deterioration. The present study draws a comparison between pharmacological (lipid-lowering drug probucol) and non-pharmacological (voluntary running wheel, RW) approaches for the management of hypercholesterolemia and cognitive impairments associated with the low-density lipoprotein receptor-deficient (LDLr-/) mice, a well-established rodent model of FH. We also investigated whether exposure to environmental enrichment (EE), a feasible option to increase physical activity in young mice cohort, from birth to adolescence (PN45) yields long-term behavioral changes in adult LDLr-/- mice (PN90). We observed that both probucol and RW significantly decreased total and non-HDL plasma cholesterol levels in LDLr-/- mice. Notably, only physical exercise mitigated the spatial memory deficits of LDLr-/- mice. In addition, we showed that exposure to EE from birth until the adolescence did not mitigate the spatial memory deficits of adult LDLr-/- mice in the object location task, although it induced persistent anxyolitic-like effects in the open field arena. Collectively, our results emphasize the advantages physical exercise, in comparison to lipid-lowering drugs, for the management of cognitive deficits associated with FH.
  Neuroscience Letters 03/2013; · 2.11 Impact Factor
• Article: Toxicity of ethylmercury (and Thimerosal): a comparison with methylmercury.

  José G Dórea, Marcelo Farina, João B T Rocha
  [show abstract] [hide abstract]
  ABSTRACT: Ethylmercury (etHg) is derived from the metabolism of thimerosal (o-carboxyphenyl-thio-ethyl-sodium salt), which is the most widely used form of organic mercury. Because of its application as a vaccine preservative, almost every human and animal (domestic and farmed) that has been immunized with thimerosal-containing vaccines has been exposed to etHg. Although methylmercury (meHg) is considered a hazardous substance that is to be avoided even at small levels when consumed in foods such as seafood and rice (in Asia), the World Health Organization considers small doses of thimerosal safe regardless of multiple/repetitive exposures to vaccines that are predominantly taken during pregnancy or infancy. We have reviewed in vitro and in vivo studies that compare the toxicological parameters among etHg and other forms of mercury (predominantly meHg) to assess their relative toxicities and potential to cause cumulative insults. In vitro studies comparing etHg with meHg demonstrate equivalent measured outcomes for cardiovascular, neural and immune cells. However, under in vivo conditions, evidence indicates a distinct toxicokinetic profile between meHg and etHg, favoring a shorter blood half-life, attendant compartment distribution and the elimination of etHg compared with meHg. EtHg's toxicity profile is different from that of meHg, leading to different exposure and toxicity risks. Therefore, in real-life scenarios, a simultaneous exposure to both etHg and meHg might result in enhanced neurotoxic effects in developing mammals. However, our knowledge on this subject is still incomplete, and studies are required to address the predictability of the additive or synergic toxicological effects of etHg and meHg (or other neurotoxicants). Copyright © 2013 John Wiley & Sons, Ltd.
  Journal of Applied Toxicology 02/2013; · 2.48 Impact Factor