ABSTRACT
Background: Intrathecal injection of voltage-sensitive calcium channel blocker peptide toxins exerts analgesic effect in several animal models of pain. Upon intrathecal administration, recombinant Phα1β exerts the same analgesic effects as the those of the native toxin. However, from a clinical perspective, the intrathecal administration limits the use of anesthetic drugs in patients. Therefore, this study aimed to investigate the possible antinociceptive effect of intravenous recombinant Phα1β in rat models of neuropathic pain, as well as its side effects on motor, cardiac (heart rate and blood pressure), and biochemical parameters. Methods: Male Wistar rats and male Balb-C mice were used in this study. Giotto Biotech® synthesized the recombinant version of Phα1β using Escherichia coli expression. In rats, neuropathic pain was induced by chronic constriction of the sciatic nerve and paclitaxel-induced acute and chronic pain. Mechanical sensitivity was evaluated using von Frey filaments. A radiotelemeter transmitter (TA11PA-C10; Data Sciences, St. Paul, MN, USA) was placed on the left carotid of mice for investigation of cardiovascular side effects. Locomotor activity data were evaluated using the open-field paradigm, and serum CKMB, TGO, TGP, LDH, lactate, creatinine, and urea levels were examined. Results: Intravenous administration of recombinant Phα1β toxin induced analgesia for up to 4 h, with ED50 of 0.02 (0.01-0.03) mg/kg, and reached the maximal effect (Emax = 100% antinociception) at a dose of 0.2 mg/kg. No significant changes were observed in any of the evaluated motor, cardiac or biochemical parameters. Conclusion: Our data suggest that intravenous administration of recombinant Phα1β may be feasible for drug-induced analgesia, without causing any severe side effects.
Subject(s)
Male , Animals , Rats , Analgesics , Sciatic Neuropathy/therapy , Paclitaxel , Toxins, Biological/administration & dosage , Toxins, Biological/adverse effects , Spider Venoms/chemistry , Administration, Intravenous , Mice, Inbred BALB C , Rats, WistarABSTRACT
ABSTRACT One of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive impairment is the accumulation of uremic toxins due to the deterioration of the renal clearance function. Cognition can be categorized into five major domains according to its information processing functions: memory, attention, language, visual-spatial, and executive. We performed a review using the terms 'uric acid', 'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and 'parathyroid hormone'. These are the compounds that were found to be strongly associated with cognitive impairment in CKD in the literature. The 26 selected articles point towards an association between higher levels of uric acid, homocysteine, and interleukin 6 with lower cognitive performance in executive, attentional, and memory domains. We also reviewed the hemodialysis effects on cognition. Hemodialysis seems to contribute to an amelioration of CKD-related encephalopathic dysfunction, although this improvement occurs more in some cognitive domains than in others.
RESUMO Um dos mecanismos propostos para explicar o comprometimento cognitivo relacionado à doença renal crônica (DRC) é o acúmulo de toxinas urêmicas devido à deterioração da função de depuração renal. A cognição pode ser categorizada em cinco domínios principais de acordo com suas funções de processamento de informações: memória, atenção, linguagem, visual-espacial e executiva. Realizamos uma revisão usando os termos "ácido úrico", "indoxil sulfato", "p-cresil sulfato", "homocisteína", "interleucinas" e "paratormônio". Estes são os compostos que se mostraram fortemente associados ao comprometimento cognitivo na DRC na literatura. Os 26 artigos selecionados apontam para uma associação entre níveis mais elevados de ácido úrico, homocisteína e interleucina-6 com menor desempenho cognitivo nos domínios executivo, atenção e de memória. Também revisamos os efeitos da hemodiálise na cognição. A hemodiálise parece contribuir para uma melhoria da disfunção encefalopática relacionada à DRC, embora essa melhora ocorra mais em alguns domínios cognitivos do que em outros.
Subject(s)
Humans , Toxins, Biological/adverse effects , Uremia/complications , Renal Insufficiency, Chronic/complications , Cognitive Dysfunction/etiology , Parathyroid Hormone/adverse effects , Sulfuric Acid Esters/adverse effects , Sulfuric Acid Esters/blood , Uric Acid/adverse effects , Uric Acid/blood , Renal Dialysis/adverse effects , Interleukin-6/adverse effects , Cresols/adverse effects , Cresols/blood , Interleukin-1beta/adverse effects , Interleukin-1beta/blood , Homocysteine/adverse effects , Homocysteine/blood , Indican/adverse effects , Indican/bloodABSTRACT
The scorpion toxin induces a number of physiological parameters alterations, as disturbance of cardiac rhythm, heart failure, shock, pancreatic hypersecretion, abortion, respiratory arrhytmias and pulmonary edema. As the purification of the venom fractions is a laborious process, one alternative for this would be the utilization of small animals. We utilized in the o present study thity-six mice that received progressive doses of scorpion toxin TsTX), i.p. or i.v., and were observed for three hours or sacrificed, and the pulmonary alterations were determined by the lung-body index and by histological analysis of the lungs in order to determine if the mouse can be an esperimental model for scorpion envenomation. The data were analyzed by One Way analysis of variance with p<0,05 indicating significance. These experiments showed no differences in clinical signs of scorpion envenomation between mice and other mammalians, the effects were dose-dependent and the i.v. administration needed less quantity to produce the same changings. In the pulmonary histology we observed septal but not alveolar edema, and we presumed that these differences are due to species-specific variations.
Subject(s)
Animals , Mice , Scorpion Venoms , Toxins, Biological/adverse effects , Analysis of Variance , Cheyne-Stokes Respiration , Heart BlockABSTRACT
We observed that the purified venom of the Tityus serrulatus scorpion (T1 fraction), injected IV in rats, in a single dose of 0,5 mg/kg, produces: acute pancreatitis, characterized by degranulation and acinar cell vacuolization, necrosis and an inflammatory reaction, 24, 48 and 96 hours after the injection; chronic pancreatitis, characterized by interstitial fibrosis, lymphocyte infiltration, ductal and ductular dilation, acinar cell atrophy, periductal ductular hyperplasia, 20 days after injection; hyperplasia of Langerhans' islets and nesidioblastosis, associated to chronic pancreatitis. The absence of deaths in the experimental group is an intersting finding: the dose used preserved the animals from death and allowed the safe follow-up ot the progression of the provoked pancreatitis. The results led us to conclude that the toxin of Tityus serrulatus scorpion is an agent of considerable efficacy in the induction of pancreatitis in rats providing an experimental model of acute and chronic form of this disease.
Subject(s)
Animals , Male , Rats , Pancreatitis/chemically induced , Scorpion Venoms/adverse effects , Toxins, Biological/adverse effects , Acute Disease , Chronic Disease , Disease Models, Animal , Pancreatitis/pathology , Rats, Wistar , Time FactorsABSTRACT
O paciente aqui relatado apresentou um quadro de trombocitopenia, disfunçäo renal, febre, após ser ferida por larvas de borboleta; näo apresentando anormalidades neurológicas, o que caracterizaria a síndrome de Moschcowitz. O quadro de anemia hemolítica com células vermelhas fragmentadas foi positivo, o que nos levou a pensar no diagnóstico de Púrpura Trombocitopênica Trombótica (TTP), mas estudo histológico näo foi realizado. Neste presente caso, relata-se a remissäo sustentada do quadro clínico após transfusöes de sangue fresco e sessöes de hemodiálises, precocemente instituidas