Effect of endosulfan on blood glucose

Chemosphere Fol. 9, PP 119 - 121 ©Pergamon Press Ltd. 1980. Printed in Great Britain

0045-6555/S0/0201-0119~02.00/0

EFFECT OF Ei~bC~SULF;~N ~[\i BLOCu GLUCCSZ D. llisra, R.ii. Khanna, i~. Anend and K. Gopal Industrial Toxicology aesearch Centre, Post Box No. 80, !!ehatms Gandhi ilarg, Lucknow-226001, India.

SUMI J~RY Endosulfan wss administered to cats intravenously at different doses. The compound (3 and 4 mg/kg) showed m~rked rise in blood4glucose level after 15 end 30 minutes of treatment with a gradual fall upto hrs. No change in blood glucose was observed at 2.0 mg/kg dose. ~drenelectomy prevented this rise in glucose level. Ii~TRODUCTICN Administration of endosulfan* (a chlorinated insecticide of the cyclodiene group) to mice, rat and oat produces CNS stimulation followed by involuntary body tremors and general muscul~r contractions which in some instances continue uninterrupted for several hours with great severity (1,2). It would seem that under these conditions a great 2mount of both nervous ~nd muscul~r energy would be required and expended by the animal organism until a state of exhaustion is reached. This is likely to create a great demand on the glycogen reserves in the liver. The present study was undertaken to determine (A) what effect endosulfan would have on the blood glucose (B) whether effect is dependent on the dose of the compound and (C) adrenelectomy hes eny effect on the blood glucose level. I<~TERI,~LS Al'iO iTLT};ODS ~tdult healthy cats, purchased from the local sup lier were kept in ITRC animal house one week prior to exneriment for acclimatization under standard laboratory conditions. The animals were fasted for 12 hrs before the experiment. A total of 20 cats of either sex (2.5-4.5 kg) were divided into five groups of four cats e~ch and were anaesthetized with i.p. injection of sodium pentobarbital (40-60 mg/kg). The tracheas were cannulated end the animtls were ventilated with respiratory pump. First group served as controls. The cats of the other group IInd, IIIrd end IVth were injected a single intravenous dose of endosulfan (2, 3 and 4 mg/kg respectively), dissolved in propylene glycol, through a cannuls inserted into a femoral vein. To see the effect of glucocorticoid hormones on glucose level, the animals of vth group were 8drenelectomized bilaterally and were given a rest period of four hours. They were then injected e dose of 3 mg/kg i.v. endosulfan. W k . ~ -1,2,3,4,7,7-hexachlgrobicyclo-(2,2,1)-heptene-(2)-bis-(ox~nethylene)-5,6, sulphite.

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There was no apparent effect observed below 2 mg/kg dose of endosulfan. Blood wes drawn from femorel vein in heparinized tubes at O, 15 min, 30 min, 1 hr, 2 2 hr and 4 hr interval and immediately precipitated out for the estimation of lucoseo The concentration of glucose was determined by the method of Folin-wu

~3).

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~,~D DISCUSSIbI~

The administration of endosulfan (2.0 mg/kg and higher) ceused muscular t~ritchings followed by convulsions. The changes in blood glucose level with different doses of endosulfan and at various time intervals are illustr:~ted in Fig. I.

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o--.o 2 mg/kg 3 mg}/kg

200-

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60

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Fig. 1. Effect of different doses of endosulfan on blood glucose levels at various time intervals. The bars indicate standard error of the mean. No change in blood glucose level was observed with 2.0 mg/kg dose. ~iowever, at 3.0 mg/kg dose, there was a marked rise in the level at 19 min (~-~ 132%) which attained peak values at 30 min (~'~ 152%) and then began to decline, to reach control levels in 2-4 hrs. At 4.0 mg/kg dose there was a sharp rise in glucose level at 15 min (~-~146%) with a gradual fall upto 4 hrs. From our studies it seems that 3 mg/kg of endosulfan was the minimal amount necessary to produce statistically significant hyperglycemia. An intravenous administration of DDT also produced elevation in blood sugar levels in rats (4), rabbits (5). Kacew and Singhal (4) also observed an increase in the activity of gluconeogenic enzymes after DDT treatment. Adrenalectomy prevented the rise in

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blood glucose level of cat after 3 mg/kg of endosulfsn treatment. Wand (6) has also shown that rise in blood glucose was prevented by adrenalectomy in aldrin treated cats. It may be suggested that endosulfan in some manner stimulates the adrenal glands to liberate epinephrine which in turn would elevate the blood glucose. Cn the other hand, the hyperglycemia may be s physiological response to meet the critical need of brain for increased energy in the form of glucose. ~lein and Olsen (7) observed that convulsive activity is accompanied by increase in brain lactate end decrease in glycogen glucose ratio of brain to plasma glucose. Increase in blood glucose level could possibly furnish the high demand of glucose in brain which would in turn compensate to some extent for any potential decrease in brain glucose. ,~ Cil?i C ~'~L' E D G E .EN TS

The Toxicology support of assistance

authors ~,re indebted to Dr. C.R. Krishna Murti, Director, Industrial Rese~rch Centre, Lucknow for his keen interest, valuable guidance end this work. Thanks are also due to Mr. G.~.D. Gupta for technical and Zr. !W. Ab;,sd for photography.

~FERENCES I. P.K. Gupta, Bull. Environ. Contsm. Toxicol., 15 (6), 708 (1976). 2. R.N. Khanna, D. Misra, M. Anand and H.K. Sharma, Toxicol., 22, 72, (1979).

Bull. ~nviroh. Contam.

3. Folin and Wu~ Cited from hawk's physiological chemistry, Oser, 14th edn., 1052, (1965). 4. S. hacew and R.L. Singhal,

Biochem. Pharmacol.,

5. E.F. Stohlman and R.D. Lilliej 6. R.A.J. Wand~

(Received in UK 3 January 1980)

22, 47, (1973).

J. PhsrT~:acol. Exp. Ther., 93, 351, (1948).

J. Phamr~scol. Exp. Ther, 106, 423,

7. J.R. Klein and N.S. Olsen,

edited by Bernard L.

(1952).

J. Biol. Chem., 167, 747, (1947).