Partial efficacy of a Brazilian coralsnake antivenom and varespladib in neutralizing distinct toxic effects induced by sublethal Micrurus dumerilii carinicauda envenoming in rats.

In this work, we reported the efficacy of a combination of Brazilian therapeutic coralsnake antivenom (CAV) and varespladib (phospholipase A2 inhibitor - VPL) in partially neutralizing selected toxic effects of Micrurus dumerilii carinicauda coralsnake venom in rats. Venom caused local myonecrosis and systemic neurotoxicity, nephrotoxicity, and hepatotoxicity within 2 h of injection. CAV and VPL administered separately failed to prevent most of these alterations. However, a combination of CAV plus VPL offered variable protection against venom-induced coagulation disturbances, leukocytosis, and renal-hepatic morphological alterations.

Acute-phase proteins in cats with obstructive feline lower urinary tract disease.

BACKGROUND: Feline obstructive disease of the lower urinary tract (FLUTD) is a common pathologic condition of cats. It can be related to sterile inflammation, which leads to acute impairment of renal function and the accumulation of electrolytes and acid-base imbalance. Acute-phase proteins (APPs) are biomarkers of tissue damage from inflammation that assist in monitoring treatment and prognosis. OBJECTIVE: Monitoring the inflammatory processes of obstructive feline lower urinary tract disease through the determination of plasma fibrinogen concentrations and serum concentrations of the acute-phase proteins, serum amyloid A (SAA), alpha-1-acid glycoprotein (AGP), and albumin. METHODOLOGY: Twenty-five male cats were included in this study. They were divided into two experimental groups: a control group (CG) and an obstruction group (OG). There were 8 healthy cats in the CG group and 17 cats with obstructive FLUTD in the OG group. APP measurements were conducted using ELISA kits. Samples were collected for APP analyses, serum biochemical assays, urinalyses, and urine protein: creatinine ratio calculations at diagnosis, before urethral clearance (H0), and 12 (H12), 24 (H24), and 48 (H48) hours after urethral clearance from cats in the OG group. Samples were collected once from cats in the CG group cats. RESULTS: At H0, we found positive correlations of SAA, AGP, and fibrinogen with urea and creatinine, and negative correlations of albumin with hematuria, SAA, and potassium. At H48, we found positive correlations between SAA and AGP, AGP and urea, fibrinogen and urea, fibrinogen and creatinine, fibrinogen and AGP, and fibrinogen and SAA. In addition, a negative correlation of albumin with urea and creatinine was observed. CONCLUSIONS: Serum amyloid A, AGP, fibrinogen, and albumin could be used as biomarkers of inflammatory processes in cats with obstructive FLUTD.

In vivo treatment with varespladib, a phospholipase A2 inhibitor, prevents the peripheral neurotoxicity and systemic disorders induced by Micrurus corallinus (coral snake) venom in rats.

In this study, we investigated the action of varespladib (VPL) alone or in combination with a coral snake antivenom (CAV) on the local and systemic effects induced by Micrurus corallinus venom in rats. Adult male Wistar rats were exposed to venom (1.5 mg/kg - i.m.) and immediately treated with CAV (antivenom:venom ratio 1:1.5 'v/w' - i.p.), VPL (0.5 mg/kg - i.p.), or both of these treatments. The animals were monitored for 120 min and then anesthetized to collect blood samples used for haematological and serum biochemical analysis; after euthanasia, skeletal muscle, renal and hepatic tissue samples were collected for histopathological analysis. M. corallinus venom caused local oedema without subcutaneous haemorrhage or apparent necrosis formation, although there was accentuated muscle morphological damage; none of the treatments prevented oedema formation but the combination of CAV and VPL reduced venom-induced myonecrosis. Venom caused neuromuscular paralysis and respiratory impairment in approximately 60 min following envenomation; CAV alone did not prevent the neurotoxic action, whereas VPL alone prevented neurotoxic symptoms developing as did the combination of CAV and VPL. Venom induced significant increase of serum CK and AST release, mostly due to local and systemic myotoxicity, which was partially prevented by the combination of CAV and VPL. The release of hepatotoxic serum biomarkers (LDH and ALP) induced by M. corallinus venom was not prevented by CAV and VPL when individually administered; their combination effectively prevented ALP release. The venom-induced nephrotoxicity (increase in serum creatinine concentration) was prevented by all the treatments. VPL alone or in combination with CAV significantly prevented the venom-induced lymphocytosis. In conclusion, VPL shows to be effective at preventing the neurotoxic, nephrotoxic, and inflammatory activities of M. corallinus venom. In addition, VPL acts synergistically with antivenom to prevent a number of systemic effects caused by M. corallinus venom.

Protective action of N-acetyl-L-cysteine associated with a polyvalent antivenom on the envenomation induced by Lachesis muta muta (South American bushmaster) in rats.

In this study, we examined the potential use of N-acetyl-L-cysteine (NAC) in association with a polyvalent antivenom and as stand-alone therapy to reduce the acute local and systemic effects induced by Lachesis muta muta venom in rats. Male Wistar rats (300-350 g) were exposed to L. m. muta venom (1.5 mg/kg - i.m.) and subsequently treated with anti-Bothrops/Lachesis serum (antivenom:venom ratio 1:3 'v/w' - i.p.) and NAC (150 mg/kg - i.p.) separately or in association; the animals were monitored for 120 min to assess changes in temperature, locomotor activity, local oedema formation and the prevalence of haemorrhaging. After this time, animals were anesthetized in order to collect blood samples through intracardiac puncture and then euthanized for collecting tissue samples; the hematological-biochemical and histopathological analyses were performed through conventional methods. L. m. muta venom produced pronounced local oedema, subcutaneous haemorrhage and myonecrosis, with both antivenom and NAC successfully reducing the extent of the myonecrotic lesion when individually administered; their association also prevented the occurrence of subcutaneous haemorrhage. Venom-induced creatine kinase (CK) release was significantly prevented by NAC alone or in combination with antivenom; NAC alone failed to reduce the release of hepatotoxic (alanine aminotransferase) and nephrotoxic (creatinine) serum biomarkers induced by L. m. muta venom. Venom induced significant increase of leucocytes which was also associated with an increase of neutrophils, eosinophils and monocytes; antivenom and NAC partially reduced these alterations, with NAC alone significantly preventing the increase of eosinophils whereas neither NAC or antivenom prevented the increase in monocytes. Venom did not induce changes in the erythrogram parameters. In the absence of a suitable antivenom, NAC has the potential to reduce a number of local and systemic effects caused by L. m. muta venom.