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      Effects of Tityus stigmurus (Thorell 1876) (Scorpiones: Buthidae) venom in isolated perfused rat kidneys

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          Abstract

          ABSTRACT Scorpions belonging to the Tityus genus are of medical interest in Brazil. Among them, Tityus stigmurus is the main scorpion responsible for stings in the Northeast region. After a sting, the scorpion venom distributes rapidly to the organs, reaching the kidneys quickly. However, there are few studies concerning the renal pathophysiology of scorpion poisoning. In this study, we evaluated the effects of T. stigmurus venom (TsV) on renal parameters in isolated rat kidneys. Wistar rats (n = 6), weighing 250-300 g, were perfused with Krebs-Henseleit solution containing 6 g/100 mL bovine serum albumin. TsV at 0.3 and 1.0 μg/mL was tested, and the effects on perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and electrolyte excretion were analyzed. Effects were observed only at TsV concentration of 1.0 μg/mL, which increased PP (controlPP40' = 92.7 ± 1.95; TsVPP40' = 182.0 ± 4.70* mmHg, *p < 0.05), RVR (controlRVR40' = 3.28 ± 0.23 mmHg; TstRVR40' = 6.76 ± 0.45* mmHg, *p < 0.05), UF (controlUF50' = 0.16 ± 0.04; TstUF50' = 0.60 ± 0.10* mL/g/min,*p < 0.05), GFR and electrolyte excretion, with histological changes that indicate renal tubular injury. In conclusion, T. stigmurus venom induces a transient increase in PP with tubular injury, both of which lead to an augmented electrolyte excretion.

          Translated abstract

          RESUMO Os escorpiões de interesse médico no Brasil pertencem ao gênero Tityus. Dentre eles, Tityus stigmurus é o principal responsável por picadas de escorpião na região Nordeste. Após uma picada, a peçonha de escorpião se distribui rapidamente para os órgãos, atingindo os rins depressa. Entretanto, há poucos trabalhos sobre fisiopatologia renal do envenenamento por escorpiões. Neste trabalho, avaliamos os efeitos da peçonha de T. stigmurus (TsV) sobre parâmetros renais em rins de ratos isolados. Ratos Wistar (n = 6), pesando 250-300 g, foram perfundidos com solução de Krebs-Henseleit contendo 6 g/100 mL de albumina de soro bovino. TsV nas concentrações de 0,3 e 1,0 μg/mL foi testado e os efeitos sobre a pressão de perfusão (PP), resistência vascular renal (RVR), fluxo urinário (FU), taxa de filtração glomerular (TFG) e excreção de eletrólitos foram analisados. Apenas na concentração de 1,0 μg/mL de TsV foram observados efeitos que aumentaram PP (controlePP40' = 92,7 ± 1,95; TsVPP40' = 182,0 ± 4,70 mmHg*, *p < 0,05), RVR (controleRVR40' = 3,28 ± 0,23 mmHg; TstRVR40' = 6,76 ± 0,45 mmHg*, *p < 0,05), FU (controleFU50' = 0,16 ± 0,04; TstFU50' = 0,60 ± 0,10 mL/g/min*, *p < 0,05), a TFG e excreção de eletrólitos, com alterações histológicas que indicam de lesão renal tubular. Em conclusão, peçonha de T. stigmurus induz um aumento transiente da PP com lesão tubular, ambos os quais conduzem a uma excreção elevada de eletrólitos.

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          Mitochondria and calcium: from cell signalling to cell death.

          M R Duchen (2000)
          While a pathway for Ca2+ accumulation into mitochondria has long been established, its functional significance is only now becoming clear in relation to cell physiology and pathophysiology. The observation that mitochondria take up Ca2+ during physiological Ca2+ signalling in a variety of cell types leads to four questions: (i) 'What is the impact of mitochondrial Ca2+ uptake on mitochondrial function?' (ii) 'What is the impact of mitochondrial Ca2+ uptake on Ca2+ signalling?' (iii) 'What are the consequences of impaired mitochondrial Ca2+ uptake for cell function?' and finally (iv) 'What are the consequences of pathological [Ca2+]c signalling for mitochondrial function?' These will be addressed in turn. Thus: (i) accumulation of Ca2+ into mitochondria regulates mitochondrial metabolism and causes a transient depolarisation of mitochondrial membrane potential. (ii) Mitochondria may act as a spatial Ca2+ buffer in many cells, regulating the local Ca2+ concentration in cellular microdomains. This process regulates processes dependent on local cytoplasmic Ca2+ concentration ([Ca2+]c), particularly the flux of Ca2+ through IP3-gated channels of the endoplasmic reticulum (ER) and the channels mediating capacitative Ca2+ influx through the plasma membrane. Consequently, mitochondrial Ca2+ uptake plays a substantial role in shaping [Ca2+]c signals in many cell types. (iii) Impaired mitochondrial Ca2+ uptake alters the spatiotemporal characteristics of cellular [Ca2+]c signalling and downregulates mitochondrial metabolism. (iv) Under pathological conditions of cellular [Ca2+]c overload, particularly in association with oxidative stress, mitochondrial Ca2+ uptake may trigger pathological states that lead to cell death. In the model of glutamate excitotoxicity, microdomains of [Ca2+]c are apparently central, as the pathway to cell death seems to require the local activation of neuronal nitric oxide synthase (nNOS), itself held by scaffolding proteins in close association with the NMDA receptor. Mitochondrial Ca2+ uptake in combination with NO production triggers the collapse of mitochondrial membrane potential, culminating in delayed cell death.
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            Overview of scorpion toxins specific for Na+ channels and related peptides: biodiversity, structure-function relationships and evolution.

            Scorpion venoms contain a large number of bioactive components. Several of the long-chain peptides were shown to be responsible for neurotoxic effects, due to their ability to recognize Na(+) channels and to cause impairment of channel functions. Here, we revisited the basic paradigms in the study of these peptides in the light of recent data concerning their structure-function relationships, their functional divergence and extant biodiversity. The reviewed topics include: the criteria for classification of long-chain peptides according to their function, and a revision of the state-of-the-art knowledge concerning the surface areas of contact of these peptides with known Na(+) channels. Additionally, we compiled a comprehensive list encompassing 191 different amino acid sequences from long-chain peptides purified from scorpion venoms. With this dataset, a phylogenetic tree was constructed and discussed taking into consideration their documented functional divergence. A critical view on problems associated with the study of these scorpion peptides is presented, drawing special attention to the points that need revision and to the subjects under intensive research at this moment, regarding scorpion toxins specific for Na(+) channels and the other related long-chain peptides recently described.
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              Manual de diagnóstico e tratamento de acidentes por animais peçonhentos.

              (2001)
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
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                Journal
                aabc
                Anais da Academia Brasileira de Ciências
                An. Acad. Bras. Ciênc.
                Academia Brasileira de Ciências
                1678-2690
                2016
                : 88
                : suppl 1
                : 665-675
                Affiliations
                [1 ] Universidade Federal de Pernambuco Brazil
                [2 ] Faculdade de Medicina Brasil
                [3 ] Universidade Federal de Pernambuco Brazil
                [4 ] Universidade Federal do Ceará Brazil
                [5 ] Universidade Federal do Ceará Brazil
                [6 ] Universidade Federal de Pernambuco Brazil
                [7 ] Universidade Federal de Pernambuco Brazil
                Article
                S0001-37652016000200665
                10.1590/0001-3765201620150253
                65d0161f-4cf0-444e-8f22-e455dd7d25b4

                This work is licensed under a Creative Commons Attribution 4.0 International License.

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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0001-3765&lng=en
                Categories
                MULTIDISCIPLINARY SCIENCES

                2D-PAGE,kidney,MDCK,venom,Tityus stigmurus,rim,veneno
                2D-PAGE, kidney, MDCK, venom, Tityus stigmurus, rim, veneno

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