Renal and antibacterial effects induced by myotoxin I and II isolated from Bothrops jararacussu venom.
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 PLA2) and II (Asp49 PLA2) and their possible blockage by indomethacin. BthTX-I (5 microg/ml) and BthTX-II (5 microg/ml) increased perfusion pressure (PP; ct120=110.28+/-3.70 mmHg; BthTX I=171.28+/-6.30*mmHg; BthTX II=175.50+/-7.20*mmHg), renal vascular resistance (RVR; ct120=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+/-0.01ml 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; ct120=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(+);ct120=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 (rho-BPB) decrease significantly the antibacterial effect of both PLA2. 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 PLA2.
Barbosa
P S F
PS
Institute of Biomedicine and Clinical Research Unit, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
Martins
A M C
AM
Havt
A
A
Toyama
Daniela O
DO
Evangelista
J S A M
JS
Ferreira
D P P
DP
Joazeiro
P P
PP
Beriam
Luis O S
LO
Toyama
Marcos H
MH
Fonteles
M C
MC
Monteiro
H S A
HS
D000098:Acetophenones / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D017837:Bothrops; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D003435:Crotalid Venoms / Q000737:chemistry*; D054501:Group II Phospholipases A2; D007213:Indomethacin / Q000494:pharmacology; D007677:Kidney Function Tests; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification* / Q000633:toxicity*; D054467:Phospholipases A2; D051381:Rats; D030162:Reptilian Proteins; D014553:Urinary Tract Physiological Phenomena / Q000187:drug effects*; D014974:Xanthomonas / Q000187:drug effects / Q000648:ultrastructure
D000098:Acetophenones; D003435:Crotalid Venoms; D030162:Reptilian Proteins; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2; C076780:myotoxin I; C006821:4-bromophenacyl bromide; D007213:Indomethacin