Pharmacological analysis of hemodynamic responses to Lachesis muta (South American bushmaster) snake venom in anesthetized rats

Counteracting Action of Coutarea hexandra (Rubiaceae) Stem Bark Extract on the Systemic Toxicity Induced by Lachesis muta muta (Viperidae: Crotalinae) Venom in Rats

“…The inflammatory activity induced by L. m. muta venom was also evidenced by increase in level of serum fibrinogen, while there was also an increase of reticulocytes most likely due to occurrence of subcutaneous haemorrhage (p <0.05 compared to G1 'control' for both of these parameters, n = 6) (Figure 4), but without affecting the erythrocyte count [in mm 3 : 8.3 ± 0.3 (G1), 7.8 ± 0.3 (G2), 9.3 ± 0.2 (G3), 8.6 ± 0.2 (G4), 8.2 ± 0.2 (G5) and 8.3 ± 0.3 (G6), n = 6]. Such systemic alterations characterize the physiopathological profile produced by Lachesis venoms, as previously reported in studies with animal experimentation models [8,13,15,26] and in a human case report [36]. (p < 0.05 compared to G3 'venom' for both these biomarkers, n = 6) (Figure 2), and avoided the increase of reticulocytes release (p < 0.05 compared to G3 'venom', n = 6) (Figure 4); however, antivenom only partially prevented the venom-induced cardiotoxicity, as measured through serum CK-MB release (Figure 2) and promoted limited protection against the increase in leukocytes involved in the inflammatory responses, e.g., neutrophils, eosinophils, and monocytes (Figure 3), including a mild protection against the increase of fibrinogen (Figure 4).…”

“…Envenomations by Lachesis snakes are characterized by causing severe local damage and systemic disorders which commonly result in deaths, mostly associated with their potent cardiovascular action [8,13,15]. In this work, rats exposed to L. m. muta venom (1.5 mg/kg, i.m.)…”

“…Envenomation by Lachesis spp. causes critical local [5][6][7] and systemic disorders characterized by haematological disturbances such as widespread bleeding, coagulopathy and pulmonary thrombosis [8][9][10][11], including renal failure [12], bradycardia and hypotension [8,[13][14][15][16]. These venoms contain a wide variety of non-enzymatic proteins and peptides biologically active [17,18] including venom metalloproteases (SVMPs), serine proteases (SVSPs), phospholipases A 2 (PLA2), C-type lectins and L-amino acid oxidase (LAAO), which are directly related to envenomation process by Lachesis spp.…”

Action of Varespladib (LY-315920), a Phospholipase A2 Inhibitor, on the Enzymatic, Coagulant and Haemorrhagic Activities of Lachesis muta rhombeata (South-American Bushmaster) Venom

“…In Brazil, these snakes are represented by three main genera, i.e., Bothrops , Crotalus and Lachesis (Viperidae–Crotalinae), being responsible for more than 20,000 cases of snakebites per year in this country, as reported by Notifiable Diseases Information System of the Brazilian Ministry of Health (SINAN, Brasília, DF, Brazil). Lachesis snakes found in South America ( L. muta muta and L. m. rhombeata ) occasionally cause severe human envenomations ( Magalhães et al, 2019 ; Diniz-Sousa et al, 2020 ), which are characterized by pronounced local and systemic disorders, e.g., necrosis ( Damico et al, 2006 ; Ferreira et al, 2009 ; Damico et al, 2012 ), haemorrhage, coagulopathy ( Sánchez et al, 1987 ; Sánchez et al, 1991 ; Sánchez et al, 1995 ; Fuly et al, 1997 ; Rucavado et al, 1999 ; Estêvão-Costa et al, 2000 ; Torres-Huaco et al, 2013 ) and hypotension ( Dias et al, 2016a ; Dias et al, 2016b ), strongly associated with a variety of enzymatically active proteins such as snake venom metalloproteases, serine proteases, PLA 2 , C-type lectins and l -amino acid oxidases ( Weinberg et al, 2004 ; Junqueira-de-Azevedo et al, 2006 ; Bregge-Silva et al, 2012 ; Madrigal et al, 2012 ; Cordeiro et al, 2018 ; Diniz-Sousa et al, 2018 ; Wiezel et al, 2019 ) present in these venoms.…”

“…Envenomation by Lachesis spp. is characterized by intense local pain, oedema and necrosis (Damico et al, 2006;Ferreira et al, 2009;Damico et al, 2012), systemic myotoxicity (Fuly et al, 2000;Fuly et al, 2003;Damico et al, 2006), renal failure (Damico et al, 2007), haemorrhage and coagulopathy (Sánchez et al, 1987;Sánchez et al, 1991;Sánchez et al, 1995;Fuly et al, 1997;Rucavado et al, 1999;Estêvão-Costa et al, 2000;Torres-Huaco et al, 2013), including severe cardiovascular disorders (Diniz and Oliveira, 1992;Giovanni-De-Simone et al, 1997;Dias et al, 2016a;Dias et al, 2016b). Such effects have been associated predominantly with the presence of phospholipases A 2 (PLA 2 ) (Cordeiro et al, 2015;Diniz-Sousa et al, 2018), metalloproteases (Cordeiro et al, 2018) and serine proteases (Wiezel et al, 2019), including biologically active peptides (Graham et al, 2005;Soares et al, 2005;Sanz et al, 2008;Pla et al, 2013;Pinheiro-Júnior et al, 2018), in these venoms.…”