ABSTRACT
The most abundant protein families in viper venoms are Snake Venom Metalloproteases (SVMPs), Snake Venom Serine Proteases (SVSPs) and Phospholipases (PLA2s). These are primarily responsible for the pathophysiology caused by the bite of pit-vipers; however, there are few studies that analyze the pharmacokinetics (PK) of whole venom (WV) and its protein families. We studied the pathophysiology, PK profile and differential absorption of representative toxins from venom of Neotropical Rattlesnake (Crotalus simus) in a large animal model (ovine). Toxins studied included crotoxin (the main lethal component), which causes moderate to severe neurotoxicity; SVSPs, which deplete fibrinogen; and SVMPs, which cause local tissue damage and local and systemic hemorrhage. We found that Whole Venom (WV) was highly bioavailable (86%) 60 h following intramuscular (IM) injection, and extrapolation suggests that bioavailability may be as high as 92%. PK profiles of individual toxins were consistent with their physicochemical properties and expected clinical effects. Lymph cannulated animals absorbed 1.9% of WV through lymph during the first 12 h. Crotoxin was minimally detectable in serum after intravenous (IV) injection; however, following IM injection it was detected in lymph but not in blood. This suggests that crotoxin is quickly released from the blood toward its tissue targets.
Subject(s)
Crotalid Venoms/pharmacokinetics , Crotalus , Lymph/metabolism , Animals , Biological Availability , Blood Coagulation/drug effects , Crotalid Venoms/administration & dosage , Crotalid Venoms/blood , Crotalid Venoms/toxicity , Crotoxin/blood , Crotoxin/pharmacokinetics , Fibrinogen/metabolism , Hemorrhage/chemically induced , Injections, Intramuscular , Injections, Intravenous , Male , Metalloproteases/blood , Metalloproteases/pharmacokinetics , Serine Proteases/blood , Serine Proteases/pharmacokinetics , Sheep, DomesticABSTRACT
Clinical and laboratory data from patients who applied a tourniquet (tourniquet group, n = 45) and who did not apply it (non-tourniquet group, n = 52) after being bitten by Crotalus durissus were compared. The patients were treated with 100-200 ml of Crotalus durissus antivenom. The gender, age, time elapsed between bite and hospital admission, dose of antivenom and the frequency of local paresthesia, myalgia and palpebral ptosis did not differ between the two groups. Plasma creatine kinase enzyme activity and partial thromboplastin time, plasma whole venom and crotoxin concentrations and the frequency of acute renal and respiratory failure and number of deaths also did not differ between both groups. Data from this study show the ineffectiveness of tourniquet applied by patients in the fields to reduce the severity of Crotalus durissus envenoming.
Subject(s)
Antivenins/therapeutic use , Crotoxin/adverse effects , Snake Bites/therapy , Tourniquets , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , Child , Child, Preschool , Creatine Kinase/blood , Crotoxin/blood , Female , Humans , Male , Middle Aged , Partial Thromboplastin Time , Renal Insufficiency/prevention & control , Respiratory Insufficiency/prevention & controlABSTRACT
Thirty-seven patients envenomed by Crotalus durissus were classified into three groups according to the interval between the bite and hospital admission (delta T): group 1 (n = 14, delta T < 4 hr), group 2 (n = 14, delta T > 4 hr < 8 hr) and group 3 (n = 9, delta T > 8 hr). Venous blood from these patients was sampled for biochemical and hematological analysis and for whole venom, crotoxin and antivenom enzyme-linked immunosorbent assays before antivenom treatment (T0) and at 1 hr (T1), 6 hr (T6), 12 hr (T12) and 24 hr (T24) after the start of antivenom therapy. The patients were treated with 100-200 ml (10-20 ampules) of C. durissus antivenom. Whole venom and crotoxin were detected in 13 (92.8%) and 11 (78.6%) of 14 group 1 patients, respectively, in 11 (78.6%) and six (42.9%) of 14 group 2 patients, respectively, and in two (22.2%) and one (11.1%) of nine group 3 patients, respectively, before antivenom treatment. Data from this study show that whole venom and crotoxin were not detected in most of patients when the time elapsed between the bite and hospital admission was greater than 8 hr, and crotoxin was not detected in most of the patients who were admitted to the hospital at times ranging from 4 to 8 hr after the snakebite. Plasma whole venom, crotoxin and antivenom levels measured over time in these patients show the efficacy of antivenom treatment, since circulating venom and crotoxin were no longer detected 1 hr after antivenom therapy and high antivenom titers persisted for at least 24 hr after serotherapy.
Subject(s)
Antivenins/therapeutic use , Crotalid Venoms/blood , Crotalus , Crotoxin/blood , Snake Bites/therapy , Adolescent , Adult , Aged , Animals , Antivenins/blood , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Snake Bites/blood , Time FactorsABSTRACT
We report on an ELISA for the detection of crotoxin with a detection limit of 1-3 pg/ml of sample. Cross-reactivity with other animal venoms occurred only at concentrations above 1 microgram/ml. Serum kinetics of crotoxin were investigated in BALB/c mice after a single 10 micrograms s.c. dose of venom obtained from Crotalus durissus terrificus. Crotoxin levels were 254 +/- 141 ng/ml serum (X +/- S.E.) 15 min after venom injection, 3.9 +/- 0.5 ng/ml serum at 30 min and undetectable thereafter. The rapid clearance of crotoxin from the serum suggests that the test may be unsuitable for the clinical management of envenomation victims.