Renal and antibacterial effects induced by myotoxin I and II isolated from Bothrops jararacussu venom

• Published in: Toxicon (Oxford) Vol. 46; no. 4; pp. 376 - 386
• Main Authors: Barbosa, P.S.F., Martins, A.M.C., Havt, A, Toyama, Daniela O., Evangelista, J.S.A.M., Ferreira, D.P.P., Joazeiro, P.P., Beriam, Luis O.S., Toyama, Marcos H., Fonteles, M.C., Monteiro, H.S.A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-09-2005; Elsevier Science
• Subjects: Acetophenones - pharmacology; Amino Acid Sequence; Animal poisons toxicology. Antivenoms; Animals; Antibacterial activity; Biological and medical sciences; Bothrops; Bothrops jararacussu; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Crotalid Venoms - chemistry; Group II Phospholipases A2; Indomethacin - pharmacology; Kidney Function Tests; Mass Spectrometry; Medical sciences; Microscopy, Electron, Transmission; Molecular Sequence Data; Myotoxin; Phospholipase A 2; Phospholipases A - antagonists & inhibitors; Phospholipases A - genetics; Phospholipases A - isolation & purification; Phospholipases A - toxicity; Phospholipases A2; Rats; Renal; Reptilian Proteins; Toxicology; Urinary Tract Physiological Phenomena - drug effects; Xanthomonas - drug effects; Xanthomonas - ultrastructure; Xanthomonas axonopodis; Bothrops jararacussu; Antibacterial activity; Myotoxin; Phospholipase A 2; Renal; Phospholipase A2; Enzyme; Activity; Esterases; Phospholipase A; Kidney; Carboxylic ester hydrolases; Toxin; Striated muscle disease; Urinary system; Venom; Hydrolases; Isolation; Antibacterial agent
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2005.04.024

Bothrops jararacussu myotoxin I (BthTx-I; Lys 49) and II (BthTX-II; Asp 49) were purified by ion-exchange chromatography and reverse phase HPLC. In this work we used the isolated perfused rat kidney method to evaluate the renal effects of
B. jararacussu myotoxins I (Lys49 PLA
2) and II (Asp49 PLA
2) and their possible blockage by indomethacin. BthTX-I (5
μg/ml) and BthTX-II (5
μg/ml) increased perfusion pressure (PP; ct
120=110.28±3.70
mmHg; BthTX I=171.28±6.30*
mmHg; BthTX II=175.50±7.20*
mmHg), renal vascular resistance (RVR; ct
120=5.49
±0.54
mmHg/ml.g
−1
min
−1; BthTX I=8.62±0.37*
mmHg/ml
g
−1
min
−1; BthTX II=8.9±0.36*
mmHg/ml
g
−1
min
−1), urinary flow (UF; ct
120=0.14±0.01
ml
g
−1
min
−1; BthTX I=0.32±0.05*
ml
g
−1
min
−1; BthTX II=0.37±0.01*
ml
g
−1
min
−1) and glomerular filtration rate (GFR; ct
120=0.72±0.10
ml
g
−1
min
−1; BthTX I=0.85±0.13*
ml
g
−1
min
−1; BthTX II=1.22±0.28*
ml
g
−1
min
−1). In contrast decreased the percent of sodium tubular transport (%TNa
+; ct
120=79,76±0.56; BthTX I=62.23±4.12*; BthTX II=70.96±2.93*) and percent of potassium tubular transport (%TK
+;ct
120=66.80±3.69; BthTX I=55.76±5.57*; BthTX II=50.86±6.16*). Indomethacin antagonized the vascular, glomerular and tubular effects promoted by BthTX I and it's partially blocked the effects of BthTX II. In this work also evaluated the antibacterial effects of BthTx-I and BthTx-II against
Xanthomonas axonopodis. pv. passiflorae (Gram-negative bacteria) and we observed that both PLA2 showed antibacterial activity. Also we observed that proteins Also we observed that proteins chemically modified with 4-bromophenacyl bromide (ρ-BPB) decrease significantly the antibacterial effect of both PLA
2. In conclusion, BthTx I and BthTX II caused renal alteration and presented activity antimicrobial. The indomethacin was able to antagonize totally the renal effects induced by BthTx I and partially the effects promoted by BthTx II, suggesting involvement of inflammatory mediators in the renal effects caused by myotoxins. In the other hand, other effects could be independently of the enzymatic activity of the BthTX II and the C-terminal domain could be involved in both effects promoted for PLA
2.