Investigation of the microcirculation and the state of oxidative stress in the rat after scorpion envenomation.
1. Severe cases of scorpion envenomation (SE) generally show both respiratory and cardiocirculatory dysfunction. However, the pathophysiology of SE remains controversial. In the present study, we tried to explain the pathophysiology of the haemodynamic perturbations and cardiac failure in rats poisoned by the venom of Buthus occitanus tunetanus through a histomorphometric study of myocardial and muscular skeletal microcirculation and analysis of the oxidative stress state in order to evaluate the implication of the inflammatory process in the pathogenesis of SE. 2. Experiments were performed on 96 rats divided into 16 groups (n = 6 in each group). Two groups were used to determine the optimum conditions of venom administration and times when to measure haemodynamic parameters. The B. occitanus tunetanus venom was administered at a dose of 800 microg/kg and tissues were removed 5 and 20 min after envenomation. Six groups were used for histomorphometric study: two control groups, two poisoned groups an two melatonin-pretreated and poisoned groups. The histomorphometric study was performed on isolated hearts and skeletal muscles. The final eight groups of rats (two control groups, two envenomated groups, two control groups pretreated with melatonin and two groups pretreated and envenomated) were used to investigate the state of tissue oxidative stress during SE and to evaluate the anti-oxidant effect of melatonin on rats poisoned with B. occitanus tunetanus venom. This study was based on the determination of tissue malondialdehyde in isolated organs as an indicator of thiobarbituric acid-reactive substances (TBARS). Melatonin was injected at a dose of 5 mg/kg, i.v., 15 min before the administration of serum or venom. Data were compared using analysis of variance and Tukey's test for multiple pair-wise comparisons. 3. Five minutes after venom injection, a significant reduction in the mean relative volume of venules and arterioles in the heart and skeletal muscles of poisoned rats was noted. Twenty minutes after venom injection, these volumes were significantly increased in the heart and skeletal muscles of poisoned rats. Pretreatment of envenomated rats with melatonin resulted in a significant decrease in the mean relative volume of the venules and arterioles in the heart and skeletal muscles 5 and 20 min after venom injection compared with untreated envenomated rats. Investigation of the oxidative stress state showed a highly significant increase in TBARS in poisoned rats compared with control groups 5 and 20 min after venom injection. Melatonin pretreatment of rats poisoned with B. occitanus tunetanus venom resulted in an important and highly significant reduction of TBARS compared with untreated envenomated rats. 4. It appears from the results of the present study that administration of B. occitanus tunetanus venom engendered an excessive myocardial and skeletal muscular vasoconstriction attributed to massive catecholamine release followed by arteriolar and venular vasodilatation. This venous stasis at the muscular microcirculation could be due to myocardiac failure. However, the concomitant presence of arteriolar vasodilatation suggests an inflammatory process in the pathophysiology of SE. This process was suggested by the genesis of a state of oxidative stress in relation to the important lipoperoxidation, which was inhibited by administration of the anti-oxidant melatonin. Thus, melatonin pretreatment seemed to accentuate the first phase of vascular reactivity in envenomed rats and inhibit the second vasodilator phase observed 20 min after administration of the venom.
Sahnoun
Z
Z
Laboratory of Pharmacologie, Faculty of Medicine, Sfax, Tunisia. Zouheir.Sahnoun@fmsf.rnu.tn
Chaker-Krichen
S
S
Kassis
M
M
Hakim
A
A
Hammami
S
S
Ghozzi
H
H
Bouayed
N
N
Bellasfar
Z
Z
Zeghal
K M
KM
Rebai
T
T
D000704:Analysis of Variance; D000818:Animals; D000832:Animals, Poisonous; D007275:Injections, Intravenous; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012604:Scorpion Venoms / Q000008:administration & dosage / Q000506:poisoning*; D012605:Scorpions; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D012604:Scorpion Venoms; D017392:Thiobarbituric Acid Reactive Substances; D008550:Melatonin