Effect of crotapotin and heparin on the rat paw oedema induced by different secretory phospholipases A2

Landucci, Elen C.T.; Toyama, Marcos H.; Marangoni, Sérgio; Oliveira, Benedito; Cirino, Giuseppe; Antunes, Edson; Nucci, Gilberto De

doi:10.1016/s0041-0101(99)00143-9

Cited by 76 publications

(46 citation statements)

References 26 publications

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“…We suggest that crotapotin might interact in a less stable way, thus partially avoiding the substrate access to the catalytic site and hiding several key amino acid residues involved in the interfacial binding surface of PLA 2 s. Crotapotin isoforms from Crotalus d. collilineatus (Cdcol F3 and Cdcol F4) and Crotalus d. terrificus (CdtF5 and Cdt F7) significantly inhibit the Btae TX-I activity by approximately 60%. Our results are in agreement with findings of Landucci and co-workers [42], who reported that highly purified crotapotin can inhibit pancreatic, bee, and other snake venom PLA2, and Bonfim et al [15] and Calgarotto et al [31], who reported that crotapotins from C. d. terrificus (F7), C. d. cascavella (F3 and F4) and C. d. collilineatus (F3 and F4) decreased by 50% the catalytic activity of BJ IV PLA 2 from B. jararacussu and BmTX-I PLA 2 from B. moojeni snake venoms. Together, these results suggest that crotapotin may bind to bothropic PLA 2 in a manner similar to that from crotalic PLA 2 .…”

Section: Discussionsupporting

confidence: 94%

Biochemical Characterization of a PLA2 Btae TX-I Isolated from Bothriopsis taeniata Snake Venom: A Pharmacological and Morphological Study

Romero-Vargas¹,

Rocha²,

Cruz‐Höfling

et al. 2014

J Clin Toxicol

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In this research a preliminary identification and biochemical and biological characterization of a PLA 2 (Btae TX-I) from the venom of a viperid snake, Bothriopsis taeniata (Speckled forest pit viper) were obtained. Btae TX-I was purified by two chromatographic steps, molecular exclusion chromatography followed by analytical chromatography reverse phase HPLC. Molecular mass behaved as a homogeneous single chain protein on SDS-PAGE, confirmed by MALDI-TOF spectrometry, indicating a molecular mass of 13889.98 Da. Tryptic peptides were determined in tandem mass spectrometry and showed similarity with other myotoxic PLA 2 s. Btae TX-I belongs to the Asp49 PLA 2 class, is enzymatically active in presence of a synthetic substrate and shows a minimum sigmoidal behavior, reaching its maximal activity at pH 8.0 and 35-45°C. PLA 2 activity in presence of Mn 2+ , Mg 2+ , Cd 2+ and Zn 2+ was reduced either in presence or absence of Ca 2+ , suggesting that the arrangement of the catalytic site presents an exclusive structure for Ca 2+ . Crotalic crotapotins from rattlesnake venom has significantly inhibited (p<0.05) the enzymatic activity of Btae TX-I. In ex vivo experiment, Btae TX-I caused partial blockade of the neuromuscular transmission in chick biventer cervicis preparations in a similar way to other Bothrops species. Btae TX-I also inhibited contractures in the upper concentration (50 µg) to exogenous KCl (20 mM). Histological analysis of the biventer cervicis incubated with Btae TX-I showed that just the highest Btae TX-I PLA 2 dose (50 µg) caused almost 27.4 ± 0.3% damaged fibers. The results give evidence that the main effect of type Asp49 Btae TX-I PLA 2 from Bothriopsis taeniata is at the post-synaptic site.

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Section: Discussionsupporting

confidence: 94%

Biochemical Characterization of a PLA2 Btae TX-I Isolated from Bothriopsis taeniata Snake Venom: A Pharmacological and Morphological Study

Romero-Vargas¹,

Rocha²,

Cruz‐Höfling

et al. 2014

J Clin Toxicol

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“…PLA 2 (30 µg/paw), a major inflammatory component of BV (12% of dry wt), transiently evokes paw edema after subplantar injection [14,22]. As indicated above melittin has also been reported to induce paw edema after plantar injection in mice [22].…”

Section: The Effect Of Bv Injection In Normal Animalsmentioning

confidence: 84%

“…One postulated mechanism involves the inhibition of Phospholipase A 2 (PLA 2 ). PLA 2 is one of the major inflammatory components of BV (12% of dry wt) and has been shown to evoke paw edema after subplantar injection [14,22]. However, Saini and co-workers have reported that melittin, a major component of BV (50% of dry wt), binds to secretory PLA 2 and inhibits its enzymatic activity which serves to suppress inflammation [33].…”

mentioning

confidence: 99%

Bee Venom Pretreatment Has Both an Antinociceptive and Anti-Inflammatory Effect on Carrageenan-Induced Inflammation.

et al. 2001

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ABSTRACT. Although the injection of bee venom (BV) has been reported to evoke tonic pain and hyperalgesia, there is conflicting evidence in the literature indicating that BV can also exert an anti-inflammatory and antinociceptive effects on inflammation. In this regard, BV has been traditionally used in Oriental medicine to relieve pain and to treat chronic inflammatory diseases such as rheumatoid arthritis. The present study was designed to test the hypothesis that BV induces acute nociception under normal conditions, but that it can serve as a potent anti-inflammatory and antinociceptive agent in a localized inflammatory state. The experiments were designed to evaluate the effect of BV pretreatment on carrageenan (CR)-induced acute paw edema and thermal hyperalgesia. In addition, spinal cord Fos expression induced by peripheral inflammation was quantitatively analyzed. In normal animals subcutaneous BV injection into the hindlimb was found to slightly increase Fos expression in the spinal cord without producing detectable nociceptive behaviors or hyperalgesia. In contrast pretreatment with BV (0.8 mg/kg) 30 min prior to CR injection suppressed both the paw edema and thermal hyperalgesia evoked by CR. In addition, there was a positive correlation between the percent change in paw volume and the expression of Fos positive neurons in the spinal cord. These results indicate that BV pretreatment has both antinociceptive and anti-inflammatory effects in CRinduced inflammatory pain. These data also suggest that BV administration may be useful in the treatment of the pain and edema associated with chronic inflammatory diseases. It has been recently reported that unilateral, subcutaneous injection of bee venom (BV) into the plantar surface of the hindpaw evokes prolonged and tonic behavioral responses resembling clinical persistent pain [6,23]. Moreover, intraplantar BV injection induces Fos expression in the ipsilateral dorsal horn of the spinal cord and the spinal Fos expression induced by BV is attenuated by morphine treatment [25]. These data suggest that BV can be a useful agent not only for assessing the mechanisms of pain transmission, but also for evaluating the effectiveness of novel analgesic drugs in the treatment of tonic pain. Although intraplantar BV injection can produce persistent pain under normal conditions, there are conflicting data indicating that BV can be both anti-inflammatory and antinociceptive under conditions of inflammation. In this regard it is interesting to note that BV therapy has been utilized as a traditional alternative medical approach to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis in humans [1,3]. In experimental animals, adjuvant induced arthritis has been shown to be successfully suppressed by long-term BV treatment [8,12]. BV or its constituents have also been reported to be effective in the treatment of rheumatoid arthritis in humans [37]. Recently, we also demonstrated that that BV treatment produced antinociceptive and anti-inflammatory effect...

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“…Results were expressed as increase or reduction in paw volume (mL) calculated by subtracting the basal volume measured at 0 min. Area under the curve (AUC) was expressed in arbitrary units (Landucci et al, 1995).…”

Section: Paw-edema Modelmentioning

confidence: 99%

In vivoanti-inflammatory effect of a sulfated polysaccharide isolated from the marine brown algaeLobophora variegata

Siqueira

Silva

Alencar

et al. 2010

Pharmaceutical Biology

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Effect of crotapotin and heparin on the rat paw oedema induced by different secretory phospholipases A2

Cited by 76 publications

References 26 publications

Biochemical Characterization of a PLA2 Btae TX-I Isolated from Bothriopsis taeniata Snake Venom: A Pharmacological and Morphological Study

Biochemical Characterization of a PLA2 Btae TX-I Isolated from Bothriopsis taeniata Snake Venom: A Pharmacological and Morphological Study

Bee Venom Pretreatment Has Both an Antinociceptive and Anti-Inflammatory Effect on Carrageenan-Induced Inflammation.

In vivoanti-inflammatory effect of a sulfated polysaccharide isolated from the marine brown algaeLobophora variegata

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