| Journal of Theoretical & Experimental Pharmacology ISSN (electronic): 1916-6958 |
Editorial: In this issue: four outstanding scientific contributions to the journal in the form of review papers
and original studies in experimental animal models
J Theor Exp Pharmacol 2010; 1 (2): 37-38
Alejandro A. NAVA-OCAMPO(a,b)
(a)PharmaReasons, Toronto, Canada
(b)Department of Pharmacology & Toxicology, Faculty of Medicine, University of Toronto, Toronto, Canada
Correspondence: editor.jtep@premiumreasons.com
and original studies in experimental animal models
J Theor Exp Pharmacol 2010; 1 (2): 37-38
Alejandro A. NAVA-OCAMPO(a,b)
(a)PharmaReasons, Toronto, Canada
(b)Department of Pharmacology & Toxicology, Faculty of Medicine, University of Toronto, Toronto, Canada
Correspondence: editor.jtep@premiumreasons.com
REVIEW ARTICLE: Pharmacological strategies to counteract doxorubicin-induced cardiotoxicity: the role
of mitochondria
J Theor Exp Pharmacol 2010; 1 (2): 39-53
Gonçalo C. PEREIRA and Paulo J. OLIVEIRA*
Center for Neurosciences and Cell Biology, Department of Zoology, University of Coimbra, Portugal
*Corresponding author: pauloliv@ci.uc.pt
ABSTRACT
Since the discovery of doxorubicin (DOX) as a potential anticancer agent, different types of human
cancers have been successfully treated. However, the use of the drug leads to an irreversible and
dose-dependent cumulative cardiotoxicity thus restraining the treatment efficacy. Previous studies
pointed out mitochondrial dysfunction as the main mechanism for drug cardiotoxicity, although the story
still remains incomplete. Several approaches have been proposed in order to prevent DOX selective
cardiotoxicity, some of which specifically target mitochondria. The present review performs a brief
overview of the mitochondrial tar-gets of DOX toxicity and the pharmacological strategies designed to
decrease it, with a special focus on agents that act on mitochondria. This review is thus divided in to three
main sections: a) the effects of DOX on mitochondrial physiology and bioenergetics as well as the
consequences at the myocyte level; b) non-pharmacological strategies already demonstrated to
counteract DOX-induced cardiotoxicity and, c) damage-preventing approaches involving mitochondria and
their mechanism. Our objective was to review the state-of-art regarding the mechanisms of DOX-induced
cardiotoxicity, especially focusing on mitochondria, and to describe strategies aimed at preventing such
toxicity. The present review can help on the development of new strategies to counteract DOX toxicity
focusing on the mitochondria as the target.
of mitochondria
J Theor Exp Pharmacol 2010; 1 (2): 39-53
Gonçalo C. PEREIRA and Paulo J. OLIVEIRA*
Center for Neurosciences and Cell Biology, Department of Zoology, University of Coimbra, Portugal
*Corresponding author: pauloliv@ci.uc.pt
ABSTRACT
Since the discovery of doxorubicin (DOX) as a potential anticancer agent, different types of human
cancers have been successfully treated. However, the use of the drug leads to an irreversible and
dose-dependent cumulative cardiotoxicity thus restraining the treatment efficacy. Previous studies
pointed out mitochondrial dysfunction as the main mechanism for drug cardiotoxicity, although the story
still remains incomplete. Several approaches have been proposed in order to prevent DOX selective
cardiotoxicity, some of which specifically target mitochondria. The present review performs a brief
overview of the mitochondrial tar-gets of DOX toxicity and the pharmacological strategies designed to
decrease it, with a special focus on agents that act on mitochondria. This review is thus divided in to three
main sections: a) the effects of DOX on mitochondrial physiology and bioenergetics as well as the
consequences at the myocyte level; b) non-pharmacological strategies already demonstrated to
counteract DOX-induced cardiotoxicity and, c) damage-preventing approaches involving mitochondria and
their mechanism. Our objective was to review the state-of-art regarding the mechanisms of DOX-induced
cardiotoxicity, especially focusing on mitochondria, and to describe strategies aimed at preventing such
toxicity. The present review can help on the development of new strategies to counteract DOX toxicity
focusing on the mitochondria as the target.
REVIEW ARTICLE: A critical overview of clinical and experimental studies on pulmonary vasodilators in
newborns
J Theor Exp Pharmacol 2010; 1 (2): 54-61
Miguel GONZÁLEZ-LOZANO(a), Alejandro A. NAVA-OCAMPO(b,c), María Elena TRUJILLO-ORTEGA(e),
María ALONSO-SPILSBURY(d), Daniel MOTA-ROJAS(d)*
(a)Postgraduate Division of Animal Science and Health, Faculty of Veterinary and Animal Production,
Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico, (b)PharmaReasons, To-ronto,
Canada, (c)Department of Pharmacology & Toxicology, Faculty of Medicine, University of Toronto,
Toronto, Canada, (d)Department of Animal Production & Agriculture, Cuerpo Académico Etología,
Producción Porcina y Fauna Silvestre. Área de Investigación: Ecodesarrollo de la Producción Animal,
Universidad Autónoma Metropolitana-Xochimilco, Mexico and (e)Animal Production: Swine, FMVZ,
Universidad Nacional Autónoma de México, Ciudad Universitaria. Mexico.
*Corresponding author: dmota100@yahoo.com.mx
ABSTRACT
Pulmonary vasodilators represent a viable alternative in the reduction of neonatal mortality and
improvement of postnatal performance. The high rate of babies born with respiratory problems facilitates
a prompt evaluation of pharmacological alternatives. This review describes the assessment of pulmonary
vasodilators in animal models as well as in some clinical trials. The studies reviewed suggest that the use
of experimental animal models is critical for examining, in depth, current alternatives of pulmonary
vasodilators intended to be used in human neonates as well as for developing new therapeutic options.
However, interspecies differences should be considered when evaluating the mechanisms involved in
perinatal asphyxia, its consequences, and treatment. Regarding drug therapy, the administration of
tocolytic agents for increasing gestational age has not shown to improve neonatal conditions. Instead,
transferring the mother to a tertiary-care centre with proper neonatal facilities. Currently, the pulmonary
vasodilator of choice in neonates with pulmonary hypertension is inhaled nitric oxide (iNO). However,
sildenafil has shown to be a good alternative both as a single drug or associated with iNO.
newborns
J Theor Exp Pharmacol 2010; 1 (2): 54-61
Miguel GONZÁLEZ-LOZANO(a), Alejandro A. NAVA-OCAMPO(b,c), María Elena TRUJILLO-ORTEGA(e),
María ALONSO-SPILSBURY(d), Daniel MOTA-ROJAS(d)*
(a)Postgraduate Division of Animal Science and Health, Faculty of Veterinary and Animal Production,
Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico, (b)PharmaReasons, To-ronto,
Canada, (c)Department of Pharmacology & Toxicology, Faculty of Medicine, University of Toronto,
Toronto, Canada, (d)Department of Animal Production & Agriculture, Cuerpo Académico Etología,
Producción Porcina y Fauna Silvestre. Área de Investigación: Ecodesarrollo de la Producción Animal,
Universidad Autónoma Metropolitana-Xochimilco, Mexico and (e)Animal Production: Swine, FMVZ,
Universidad Nacional Autónoma de México, Ciudad Universitaria. Mexico.
*Corresponding author: dmota100@yahoo.com.mx
ABSTRACT
Pulmonary vasodilators represent a viable alternative in the reduction of neonatal mortality and
improvement of postnatal performance. The high rate of babies born with respiratory problems facilitates
a prompt evaluation of pharmacological alternatives. This review describes the assessment of pulmonary
vasodilators in animal models as well as in some clinical trials. The studies reviewed suggest that the use
of experimental animal models is critical for examining, in depth, current alternatives of pulmonary
vasodilators intended to be used in human neonates as well as for developing new therapeutic options.
However, interspecies differences should be considered when evaluating the mechanisms involved in
perinatal asphyxia, its consequences, and treatment. Regarding drug therapy, the administration of
tocolytic agents for increasing gestational age has not shown to improve neonatal conditions. Instead,
transferring the mother to a tertiary-care centre with proper neonatal facilities. Currently, the pulmonary
vasodilator of choice in neonates with pulmonary hypertension is inhaled nitric oxide (iNO). However,
sildenafil has shown to be a good alternative both as a single drug or associated with iNO.
ORIGINAL RESEARCH: Behavioral and neurochemical evaluation in rats withdrawn from repeated
cocaine treatment and exposed to the forced swimming and open field tests
J Theor Exp Pharmacol 2010; 1 (2): 62-71
Maria Izabel GOMES SILVA, Maria do Carmo DE OLIVEIRA CITÓ, Jeferson FALCÃO DO AMARAL,
Manuel Rufino DE AQUINO NETO, Brinell ARCANJO MOURA, Patrícia FREIRE DE VASCONCELOS,
Silvânia Maria MENDES DE VASCONCELOS, Marta Maria DE FRANÇA FONTELES, Glauce Socorro DE
BARROS VIANA, Danielle SILVEIRA MACÊDO and Francisca Cléa FLORENÇO DE SOUSA*
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará,
Fortaleza, Brazil
*Corresponding author: clea@ufc.br; cleaflorenco@yahoo.com.br
ABSTRACT
Objective: We aimed to investigate possible behavioral alterations in the forced swimming (FST) and
open field tests (OFT), and monoamine level changes in rats with-drawn for one and seven days from
repeated cocaine administration. Methods: Animals were treated once a day during a week with cocaine
20 mg kg-1 or saline (control), intraperitoneally. Following one or seven days of cocaine administration,
animals were submitted to the FST or OFT, while another one was decapitated and their brain striatum
was removed for determination of dopamine (DA) and serotonin (5-HT) and their metabolites levels
determined by HPLC analysis. Results: Cocaine was able to induce a significant decrease in the
immobility time of animals in FST and a significant increase in the exploratory activity in OFT after both
withdrawal times. During the abstinence periods, monoamine levels were significantly increased, while
DA and 5-HT turnovers were decreased. Conclusions: Results indicate that 20 mg kg-1 of cocaine
administered during 7 consecutive days to rats were not sufficiently able to promote depression-like
symptoms 24 h or 7 days after treatment discontinuation.
cocaine treatment and exposed to the forced swimming and open field tests
J Theor Exp Pharmacol 2010; 1 (2): 62-71
Maria Izabel GOMES SILVA, Maria do Carmo DE OLIVEIRA CITÓ, Jeferson FALCÃO DO AMARAL,
Manuel Rufino DE AQUINO NETO, Brinell ARCANJO MOURA, Patrícia FREIRE DE VASCONCELOS,
Silvânia Maria MENDES DE VASCONCELOS, Marta Maria DE FRANÇA FONTELES, Glauce Socorro DE
BARROS VIANA, Danielle SILVEIRA MACÊDO and Francisca Cléa FLORENÇO DE SOUSA*
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará,
Fortaleza, Brazil
*Corresponding author: clea@ufc.br; cleaflorenco@yahoo.com.br
ABSTRACT
Objective: We aimed to investigate possible behavioral alterations in the forced swimming (FST) and
open field tests (OFT), and monoamine level changes in rats with-drawn for one and seven days from
repeated cocaine administration. Methods: Animals were treated once a day during a week with cocaine
20 mg kg-1 or saline (control), intraperitoneally. Following one or seven days of cocaine administration,
animals were submitted to the FST or OFT, while another one was decapitated and their brain striatum
was removed for determination of dopamine (DA) and serotonin (5-HT) and their metabolites levels
determined by HPLC analysis. Results: Cocaine was able to induce a significant decrease in the
immobility time of animals in FST and a significant increase in the exploratory activity in OFT after both
withdrawal times. During the abstinence periods, monoamine levels were significantly increased, while
DA and 5-HT turnovers were decreased. Conclusions: Results indicate that 20 mg kg-1 of cocaine
administered during 7 consecutive days to rats were not sufficiently able to promote depression-like
symptoms 24 h or 7 days after treatment discontinuation.
ORIGINAL RESEARCH: Neuroprotective effects of glycine in rats with permanent cerebral ischemia
J Theor Exp Pharmacol 2010; 1 (2): 72-75
Rebeca URIBE-ESCAMILLA(a), Krystell PADILLA-MARTÍN(a), Angélica GONZÁLEZ-MACIEL(b), Emilio
ARCH-TIRADO(a), Alejandro A. NAVA-OCAMPO(c,d), Alfonso ALFARO-RODRÍGUEZ(a)*
(a)Laboratory of Neurochemistry, National Institute of Rehabilitation, Secretaría de Salud, México DF,
Mexico,
(b)Laboratory of Electronic Microscopy, National Institute of Pediatry, Secretaría de Salud, México DF,
Mexico,
(c)Department of Pharmacology & Toxicology, University of Toronto, Toronto ON, Canada,
(d)PharmaReasons, Toronto ON, Canada
*Corresponding author: alfa1360@yahoo.com.mx
ABSTRACT
Objectives: The aim of this study was to evaluate the neuroprotective effects of glycine in an
experimental animal model of permanent brain ischemic injury. Glycine is an inhibitory neurotransmitter
amino acid that acts as neuromodulator of N-methyl-D-aspartate (NMDA) receptors, critically involved in
the process of ischemic brain injury. Methods: Twenty-four Wistar rats, 20 days old, were randomly
allocated to one of the following three groups. In Group 1: rats underwent a sham surgery where the left
carotid was visualized only; in Group 2, rats underwent permanent left carotid occlusion and received
treatment with placebo; and in Group 3, rats received glycine i.p. (40 mMol kg-1 24 h-1) for 30 days
examined by histopathology. Results: In Group 1, normal brain histopathology was observed. In Group 2,
tortuous capillary vessels were observed in the brain in addition to necrotic areas in hippocampus,
medial vestibular nucleus, piriform and cerebral cortex, and thalamus. In Group 3, histopathological
alterations were restricted to thalamus. Conclusions: Glycine administered i.p. to rats with permanent
left carotid occlusion limited the ischemic brain damage probably by increasing the neurological
availability of glycine concentration enough to prevent the desensitization of NMDA receptors and
consequently altering the cascade of events that lead to cellular death.
J Theor Exp Pharmacol 2010; 1 (2): 72-75
Rebeca URIBE-ESCAMILLA(a), Krystell PADILLA-MARTÍN(a), Angélica GONZÁLEZ-MACIEL(b), Emilio
ARCH-TIRADO(a), Alejandro A. NAVA-OCAMPO(c,d), Alfonso ALFARO-RODRÍGUEZ(a)*
(a)Laboratory of Neurochemistry, National Institute of Rehabilitation, Secretaría de Salud, México DF,
Mexico,
(b)Laboratory of Electronic Microscopy, National Institute of Pediatry, Secretaría de Salud, México DF,
Mexico,
(c)Department of Pharmacology & Toxicology, University of Toronto, Toronto ON, Canada,
(d)PharmaReasons, Toronto ON, Canada
*Corresponding author: alfa1360@yahoo.com.mx
ABSTRACT
Objectives: The aim of this study was to evaluate the neuroprotective effects of glycine in an
experimental animal model of permanent brain ischemic injury. Glycine is an inhibitory neurotransmitter
amino acid that acts as neuromodulator of N-methyl-D-aspartate (NMDA) receptors, critically involved in
the process of ischemic brain injury. Methods: Twenty-four Wistar rats, 20 days old, were randomly
allocated to one of the following three groups. In Group 1: rats underwent a sham surgery where the left
carotid was visualized only; in Group 2, rats underwent permanent left carotid occlusion and received
treatment with placebo; and in Group 3, rats received glycine i.p. (40 mMol kg-1 24 h-1) for 30 days
examined by histopathology. Results: In Group 1, normal brain histopathology was observed. In Group 2,
tortuous capillary vessels were observed in the brain in addition to necrotic areas in hippocampus,
medial vestibular nucleus, piriform and cerebral cortex, and thalamus. In Group 3, histopathological
alterations were restricted to thalamus. Conclusions: Glycine administered i.p. to rats with permanent
left carotid occlusion limited the ischemic brain damage probably by increasing the neurological
availability of glycine concentration enough to prevent the desensitization of NMDA receptors and
consequently altering the cascade of events that lead to cellular death.
| 2010; Volume 1; Issue 2 (May - August) |
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