Scorpion venom poisoning in experimental animals

Tags: free fatty acids, insulin resistance, triglycerides, L. Haghnazari Deppartment, K. Radha Krishna Murthy, Scorpion Venom, rabbits, Department of Biochemistry, Razi Institute, body weight, LTM Medical College, blood sugar, acute myocarditis, resistance, Insulin levels, insulin secretion, hyperglycemia, Insulin receptors, concentrations, hyperinsulinemia, Blood sugar levels
Content: Arch. Inst. RAZI (1994) 44/45 Scorpion Venom Poisoning in Experimental AnimaIs A. Zare·, K. Radha Krishna Murthy and L. Haghnazari Deppartment of Physiology, LTM Medical College, Sion, Bobay Summary Red scorpion (Mesobuthus tamulous concanesis, Pocock) sting produces acute myocarditis and causes death in children and adults. acute myocarditis was erperimentally produced by injection of 3 mg/kg and 4 mg/kg of body weight in dogs and rabbits, respectively. Plasma analyses showed significant increae in blood sugar and free fatty acids. The levels of insulin and cortisol were increased after 30 minutes with sharp decline after 60 min and the level of triglycerides showed significant decrease. These results suggest that scorpion venom produces autonomie storm and releases massive amount of catecholamines in blood which in tum enhance Insulin Resistance and suppress insulin secretion. Ali these may be responsible for changes in metabolism and various manifestations in envenomated animais. Introduction It is suggested that the massive release of catecholamines is the main factor for aIl the manifestations seen in scorpion venom poisoning. The reflection in glycogenolysis in liver, heart and tissues as weIl as the increase in osmotic fragility of erythrocytes are already reported from this labo In the present study we attempted to detect the effect of scorpion venom on free fatty acids, triglycerides, blood sugar, insulin and cortisol. Present address: Department of Biochemistry, Razi Institute, PO Box 11365-1558, Tehran, Iran. 67
Materials and methods For the present study 10 dogs and 8 rabbits of either sex, weighing 8 ± 3 kg and 1.5 ± 0.5 kg, respectively, were used. Scorpion venom 3 mglkg body weight in dogs and 4 mglkg body weight in rabbits was administrated subcutaneously. Blood was collected before venom injection and every 30 min up to 120 min after venom injection. The plasma was separated and processed for plasma free fatty acids(2), triglycerides(3),blood sugar(4), insulin(5) and cortisol(6). Ali the results were analysed statistically using Student paired 't' test. Results signs and symptoms of envenomation appeared within 25 to 30 minutes following venom injection. Ali the animais showed increase in salivation, lacrimation with frequent urination and defecation. Death occurred in dogs within 120-150 min and in rabbits within 2-5 h. The blood sugar and free fatty acid levels increased significantly (P<0.OO1) following venom injection. Triglycerides level was reduced significantly (P<0.05) (Table 1). The level of insulin was raised non-significantly within 30 min followed by a decline at 60 min. Level of cortisol increased significantly within 30 minutes and remained high till 60 min and then retumed to normal after 120 min. Discussion In the present study, the blood sugar level increased significantly producing hyperglycemia of animais following venom injection. These results are in conformity with our earlier studies(7, 8, 9, 10). This could be due to secretion of catecholamines and changes in insulin secretion. Insulin levels measured by radioimmunoassay were significantly elevated within 30 minutes after venom injection. This finding of hyperinsulinemia is in concurrence with the observations made by Ismail and Abd-Elsalam(7). Hyperinsulinism observed in the present study could be equated with insulin resistance. Insulin resistance could be caused by a change in the receptor number, a change in hormone-receptor binding characteristics or 68
Arch. lnst. RAZl (1994) 44/45 a change in post-receptor events. Insulin receptors probably are down regulated by high concentrations of agonist hormone. The post-receptor resistance can be caused by other hormones(ll); for instance stimulation of glucagon secretion(12) and angiotensin 11(9), (which facilitates the release of catecholamines), have been demonstrated earlier in experimental scorpion venom poisoning. These alterations in the hormonal environment possibly explain the hyperinsulinemia (insulin resistance) as shown by hyperglycemia and rise in free fatty acids. Even though these findings are in agreement with observations made by Ismail and Abd-Elsalam(7), the hyperinsulinemia noticed, is quite unexpected because sympathetic system is directly involved in the regulation of insulin secretion and during epinephrine infusion, despite hyperglycemia, insulin secretion is not stimulated( 13). Insulin levels were found to be reduced at 60 min following venom injection. These results were in conformation with our earlier reports(8, 9, 10). Catecholamines directly suppress insulin secretion. Blood Sugar Levels have been found to be increased when the poisoned animais showed reduced insulin levels. The hyperglycemia could be due to glycogenolysis as demonstrated earlier in the dog following scorpion venom poisoning(1). There was an increase in free fatty acids along with a simultaneous reduction in triglycerides level following venom injection. These results were also in support of our earlier work(8, 9, 10). The elevated free fatty acids are toxic, lead to arrhythemias and, in conditions of ischemia, will intensify the myocardial oxygen consumption(14). The elevated free fatty acids inhibit cardiac Na +-K+ ATPase activity contributing to the aberrant electrical behaviour of ischemic hearts (15). These changes are reflected by alterations in cardiac sarcolemmal ATPase activities indicating cardiac sarcolemmal defects( 16). Cortisol excess produces hyperglycaemia, glycosuria, increased resistance to insulin and an increase in liver glycogen. The hyperglycaemia thus induced in normal animal or person is to some extent counteracted by an increased secretion of insulin. Cortisol accelerates gluconeogenesis in the liver. In diabetics, cortisol raises plasma lipids and increases ketone body formation. The effect of cortisol on electrolyte and water excretion is qualitatively similar to that of aldosterone, though it is very much less potent. Thus cortisol promotes retention Na+ and excretion of K+ by the kidney. Large amounts of cortisol cause excessive retention of Na + and
Table 1. Effect of venom on dog blood sugar, insulin, free fatty acids and triglycerides (MEAN ±S.E.D.)
BEFORE
AFTER
VENOM o MIN
JO MIN
60 MIN
VENOM 90 MIN
BLOODSUGAR
(mtJtIl)
··
···
··
MEAN
119.66
248.00
J41.66
402.66
(6)
:%J8.S0
r.47.JO
r.76.J0
%CHANGES
+107
+185
+238
INSULIN
(pMIIПI/Ml)
NS
NS
·
MEAN
22.86
4J.SO
20.00
69.41
(6)
:%IJ.Jl
:%5.J2
r.22.00
9fCHANGES
+90
·12
+204
FREE FATlY AC/DS
(pmtJl/L)
NS
··
Ils
MEAN
2MBJ
62400
411.40
417.JJ
(6)
±267.00
:%41.90
±108.00
%CHANGES
+IJS
+54
+56
TRIGLYCERIDES
(mtJtIl)
·
NS
NS
MEAN
87.41
7J.8J
96.60
6J.J2
(6)
±s.s1
±4.6O
±9.S0
%CHANGES
·IS
+11
·27
··P" CHANGES: BE1WEEN BEFORE VENOM .AND All Other DBSERVAT/ONS.
S.E.D.: standard error OF MEAN DEFFERENCE.
COMPAlUSON OF RESULTS FOR BIOSTAT/ST/CAL ANALYSIS IN GROUP 1: BEFORE VENOM WTrH ALL DBSERVATIONS AFTER VENOM
120 MIN · ··· 288.00 r.l7.JO +140 NS JO.50 r.9.00 +JJ ·· 528.S0 ±97.00 +98 NS 69.01 ±10.00 ·21
70
Arch. Irut. RAZI (1994) 44/45 extracellular water leading to oedema and hypertension(17) Therefore, the excess of cortisol level in the plasma could have been a factor for insulin resistance and hyperglycaemia as weIl as hyperinsulinism in our experimental animais poisoned with scorpion venom. It was concluded that scorpion venom poisoning with multiple systems organ failure characterised by massive release of catecholamines, angiotensin II, inhibition of insulin secretion and enhanced insulin resistance is a condition of fuel energy deficits and inability to effectively utilize the existing metabolic substrate. Acknowledgements This work was financed by Indian Council of medical research (ICMR) and Haffk:ine Bio-pharmaceutical Corporation, Bombay. Abbas Zare M. was recipient of senior research fellowship from ICMR. References 1. Balasubramaniam, and Radha Krishna Murthy, K (1984). Abnormal cardiovascular and electrocardiographic profiles and cardiac glycogen content in rabbits injected with scorpion venom. Indian Journal of Physiology and Pharmacology. 25: 35-355. 2. Varley, H (1980). In: Practical Clin. Biochem. 5th ed. Arnold-Heine mann, New Delhi. 3. Gattfried, S. P., Rossenberg, B. (1980) In: Varley H Practical Clin. Biochem. 5th ed. Arnold-Heine mann, New Delhi. 4. Bittner, D. L. and Manning, J. (1967). In Automation in Analytical Chemistry. VoL 1 (White Plains, Medical Inc., New York) P. 33. 5. Bhabha Atomic Research Centre. Radioimmunoassay Kit for analysis of insulin, Bombay. 6. Endab cortisol enzyme immunoassay kit. Catalog number 107, supplied by Immunetech Corp. Boston. 7. Ismail, M, and Abd-Elsalam, MA. (1988). Are the toxicological effects of scorpion envenomation related to tissue venom concentration? Toxicon, 26: 233. 8. Radha Krishna Murty, K, Zolfagharian, H, Medh. J. D., Kudalkar, J. A., Yeolekar, ME., Pandit, S. P. Khopkar, M, Dave, K N., Billimoria, F. R r·' 71 1
(1988). Dissiminated intravascular coagulation and disturbances in carbohydrate and fat metabolism in acute myocarditis produced by scorpion (Buthustamulus) venom. Indian Journal of Medical Research. 87: 318. 9. Abbas Zare, M Scorpion Venom Poisoning: Reversai of Biochemical Hormonal and Pathophysiological Disturbances by Anti-scorpion Venom and Insulin Therapy. Ph.D. Thesis submitted to University of Bombay. 10.Radha Krishna Murthy, K Billimoria, F. R, Khopkllr, M & Dave, K N., (1986)Acute hyperglycemia and hyperkillemia in acute myocarditis produced by scorpion (Buthus tamulus) venom injection in dogs. Indian HeArt Journal. 38: 7i. 11.Izzo, J. L. Jr. (1991). Insulin resistance; Is it truly the link? Americal Journal of Medicine 90 (Supple 2A), 2A-263. 12 Johnson, D. G. and Ensincle, J. W. (1976). Stimulation of glucagon secretion by scorpion by scorpion torins in the perfused rat pancreas. Diabetes 25: 645 13 Ensincle, J. W. and Williams, R H (1972). In Handbook of Physiology, Section 7: Endocrinology, Vol. /. R O. Greep, E. B. Astwood, D. F. Steiner, and S. R Geiger, Eds (American Physiological Society, Washington, Williams and Wz1kins Company, Baltimore) P. 665. 14. VUe, H and Ole,· D. M (1981). Influence offree fatty acids on myocardial oxygen consumption and ischemic injury. Australian Journal of Cardiolology. 48: 361. 15.Lamers, J. M and Hulsman, W. C. (1977). Inhibition of Na+/C" stimulated A TPase of hearts by fatty acids. Journal of Molecular and Cell Cardiology. 9: 343. 16.Radha Krishna Murthy, K (1982). Investigations of cardiac sarcolemmal A TPase activitiy in rabbils with acute myocarditis produced by scorpion (Buthus tamulus) venom. Japanese Heart Journal 23: 835. 17.Cyril, A. K, Eric, N. and Norman J. Samson Wright's Applied Physiology, 13 ed. Oxford University Press, Delhi. 72

File: scorpion-venom-poisoning-in-experimental-animals.pdf
Published: Sun Feb 19 13:25:04 2017
Pages: 6
File size: 0.17 Mb


General Systems, 1 pages, 0.27 Mb

, pages, 0 Mb
Copyright © 2018 doc.uments.com