Can the Mortality Rate be Reduced in the Diabetes Induction Model in Rats? A Protocol Study
,
Abstract
The use of animal models of diseases is essential for the study of the effects of various drugs and the discovery of new drugs. One of the most common problems in researches on diabetes in animal models is the high rate of mortality after diabetes induction. This leads to disrupt the grouping of diabetic animals for interventional evaluations. We introduce a protocol to reduce the rate of mortality in diabetic rats. To do this, we used alloxan at dose of 185 mg/kg to induce diabetes in rats. In this study in addition to provide 5% glucose solution in drinking water from 2 to 12 hrs post alloxan injection, 2 ml of 50% dextrose solution orally gavaged with 2 hrs intervals up to 12 hrs post diabetes induction, and also from 12 to 24 hrs following alloxan injection 2 ml of 5% glucose solution was given by gavage every 2 hrs. Furthermore, from 6 to 48 hrs post alloxan injection the rats were orally received 1 ml of Ringer's serum with 2 hrs intervals via gavage route. Moreover, one unit of Novolin 70/30 (70% NPH and 30% insulin regular) was subcutaneously injected in the back of the neck area for 5 consistence days from the second day post alloxan injection. In the sixth day following alloxan injection the level of glucose was at level of 280 mg/dL which considered as diabetic level. Our findings showed that by abovementioned interventions the rate of mortality significantly reduced (2 percent) and diabetes well established.
1. Radl J, Croese J, Zurcher C, Van den Enden-Vieveen M,
de Leeuw AM. Animal model of human disease. Multiple
myeloma. Am J Pathol 1988;132:593-7.
2. Fiorellini JP, Nevins ML, Norkin A, Weber HP,
Karimbux NY. The effect of insulin therapy on
osseointegration in a diabetic rat model. Clin Oral
Implants Res 1999;10:362-8.
3. Rohilla A, Ali S. Alloxan induced diabetes: mechanisms
and effects. Int J Res pharm Biomed Sci 2012;3:819-23.
4. Balali Dehkordi S, Sajedianfard J, Owji AA. The effect of
intra-cerebroventricular injection of insulin on
nociception of formalin test in non-diabetic and shortterm diabetic rat models. Iran J Vet Res 2017;18:108-12.
5. Dhanabal S, Raja MMM, Ramanathan M, Suresh B.
Hypoglycemic activity of Nymphaea stellata leaves
ethanolic extract in alloxan induced diabetic rats.
Fitoterapia 2007;78:288-91.
6. Gidado A, Ameh D, Atawodi S. Effect of Nauclea
latifolia leaves aqueous extracts on blood glucose levels
of normal and alloxan-induced diabetic rats. African J
Biotechnol 2005;4:91-3.
7. Szkudelski T. The mechanism of alloxan and
streptozotocin action in B cells of the rat pancreas.
Physiol Res 2001;50:537-46.
8. AE Kitabchi GU, JM Miles. Hyperglycemic Crises in
Adult Patients With Diabetes. Diabetes Care
2009;32:1335-43.
9. Kawano K, Hirashima T, Mori S, Saitoh Y, Kurosumi M,
Natori T. Spontaneous long-term hyperglycemic rat with
diabetic complications: Otsuka Long-Evans Tokushima
Fatty (OLETF) strain. Diabetes 1992;41:1422-8.
10. Walter S, Skinner J, Laycock J, Shirley D. The
antidiuretic effect of chronic hydrochlorothiazide
treatment in rats with diabetes insipidus: water and
electrolyte balance. Clin Sci (Lond) 1982;63:525-32.
11. SCOW RO. Total pancreatectomy in the rat: operation,
effects, and postoperative care. Endocrinology
1957;60:359-67.
12. Alam S, Khan AH, Sirhindi GA, Khan S. Alloxan
induced diabetes in rabbits. Pakistan J Pharmacol
2005;22:41-5.
13. Miller HC. The effect of pregnancy complicated by
alloxan diabetes on the fetuses of dogs, rabbits and rats.
Endocrinology 1947;40:251-8.
14. Ghosh S, Suryawanshi SA. Effect of Vinca rosea extracts
in treatment of alloxan diabetes in male albino rats. Indian
J Exp Biol 2001;39:748-59.
15. Raju J, Gupta D, Rao AR, Yadava PK, Baquer NZ.
Trigonella foenum graecum (fenugreek) seed powder
improves glucose homeostasis in alloxan diabetic rat
tissues by reversing the altered glycolytic, gluconeogenic
and lipogenic enzymes. Mol Cell Biochem 2001;224:45-
51.
16. Dixon RL, Hart LG, Rogers LA, Fouts JR. The
Metabolism of Drugs by Liver Microsomes from
Alloxan-Diabetic Rats: Long Term Diabetes. J Pharmacol
Exp Ther 1963;142:312-7.
17. El-Demerdash FM, Yousef MI, El-Naga NIA.
Biochemical study on the hypoglycemic effects of onion
and garlic in alloxan-induced diabetic rats. Food Chem
Toxicol 2005;43:57-63.
18. Maithili V, Dhanabal SP, Mahendran S, Vadivelan R.
Antidiabetic activity of ethanolic extract of tubers of
Dioscorea alata in alloxan induced diabetic rats. Indian J
Pharmacol 2011;43:455-9.
19. Pari L, Maheswari JU. Hypoglycaemic effect of Musa
sapientum L. in alloxan-induced diabetic rats. J
Ethnopharmacol 1999;68:321-5.
20. Dhandapani S, Subramanian VR, Rajagopal S,
Namasivayam N. Hyoplipidemic effect of cuminum
cyminum cyminum L. on alloxan- induced diabetic rats.
Pharmacol Res 2002;46:251-5.
21. Abdel-Barry JA, Abdel-Hassan IA, Al-Hakiem MHH.
Hypoglycaemic and antihyperglycaemic effects of
Trigonella foenum-graecum leaf in normal and alloxan
induced diabetic rats. J Ethnopharmacol 1997;58:149-55.
22. Karen. A Layman's Guide to Health, Medication Use,
Breeding, and Responsible Care of Pet Rats. Rat Health
Guide; 2020.
23. Christensen S, Kusano E, Yusufi A, Murayama N, Dousa
TP. Pathogenesis of nephrogenic diabetes insipidus due to
chronic administration of lithium in rats. J Clin Invest
1985;75:1869-79.
24. Lubar JF, Boyce BA, Schaefer CF. Etiology of polydipsia
and polyuria in rats with septal lesions. Physiol Behav
1968;3:289-92.
25. Hills A, Chalmers T, Webster G, Rosenthal O, Conover
H, Songster E. Adrenal cortical regulation of the
distribution of water and electrolytes in the human body. J
Clin Invest 1953;32:1236-47.
26. Groenendyk S, English P, Abetz I. External balance of
water and electrolytes in the horse. Equine Vet J
1988;20:189-93.
27. Darrow DC, Yannet H. Metabolic studies of the changes
in body electrolyte and distribution of body water induced
experimentally by deficit of extracellular electrolyte. The
J Clin Invest 1936;15:419-27.
28. Weisberg HF. Water, electrolyte and acid-base balance.
Philadelphia, Pennsylvania, United States: The Williams
& Wilkins; 1953.
29. Arun N, Nalini N. Efficacy of turmeric on blood sugar
and polyol pathway in diabetic albino rats. Plant Foods
Hum Nutr 2002;57:41-52.
30. Dehkordi SB, Sajedianfard J, Owji AA. The effect of
intra-cerebroventricular injection of insulin on the levels
of monoamines on the raphe magnus nucleus of nondiabetic and short-term diabetic rats in the formalin test.
Iran J Basic Med Sci 2019;22:915
31. Fitzsimons T, Le Magnen J. Eating as a regulatory control
of drinking in the rat. J Comp Physiol Psychol
1969;67:273-83.
32. Atcha Z, Rourke C, Neo AH, Goh CW, Lim JS, Aw C-C,
et al. Alternative method of oral dosing for rats. J Am
Assoc Lab Anim Sci 2010;49:335-4
de Leeuw AM. Animal model of human disease. Multiple
myeloma. Am J Pathol 1988;132:593-7.
2. Fiorellini JP, Nevins ML, Norkin A, Weber HP,
Karimbux NY. The effect of insulin therapy on
osseointegration in a diabetic rat model. Clin Oral
Implants Res 1999;10:362-8.
3. Rohilla A, Ali S. Alloxan induced diabetes: mechanisms
and effects. Int J Res pharm Biomed Sci 2012;3:819-23.
4. Balali Dehkordi S, Sajedianfard J, Owji AA. The effect of
intra-cerebroventricular injection of insulin on
nociception of formalin test in non-diabetic and shortterm diabetic rat models. Iran J Vet Res 2017;18:108-12.
5. Dhanabal S, Raja MMM, Ramanathan M, Suresh B.
Hypoglycemic activity of Nymphaea stellata leaves
ethanolic extract in alloxan induced diabetic rats.
Fitoterapia 2007;78:288-91.
6. Gidado A, Ameh D, Atawodi S. Effect of Nauclea
latifolia leaves aqueous extracts on blood glucose levels
of normal and alloxan-induced diabetic rats. African J
Biotechnol 2005;4:91-3.
7. Szkudelski T. The mechanism of alloxan and
streptozotocin action in B cells of the rat pancreas.
Physiol Res 2001;50:537-46.
8. AE Kitabchi GU, JM Miles. Hyperglycemic Crises in
Adult Patients With Diabetes. Diabetes Care
2009;32:1335-43.
9. Kawano K, Hirashima T, Mori S, Saitoh Y, Kurosumi M,
Natori T. Spontaneous long-term hyperglycemic rat with
diabetic complications: Otsuka Long-Evans Tokushima
Fatty (OLETF) strain. Diabetes 1992;41:1422-8.
10. Walter S, Skinner J, Laycock J, Shirley D. The
antidiuretic effect of chronic hydrochlorothiazide
treatment in rats with diabetes insipidus: water and
electrolyte balance. Clin Sci (Lond) 1982;63:525-32.
11. SCOW RO. Total pancreatectomy in the rat: operation,
effects, and postoperative care. Endocrinology
1957;60:359-67.
12. Alam S, Khan AH, Sirhindi GA, Khan S. Alloxan
induced diabetes in rabbits. Pakistan J Pharmacol
2005;22:41-5.
13. Miller HC. The effect of pregnancy complicated by
alloxan diabetes on the fetuses of dogs, rabbits and rats.
Endocrinology 1947;40:251-8.
14. Ghosh S, Suryawanshi SA. Effect of Vinca rosea extracts
in treatment of alloxan diabetes in male albino rats. Indian
J Exp Biol 2001;39:748-59.
15. Raju J, Gupta D, Rao AR, Yadava PK, Baquer NZ.
Trigonella foenum graecum (fenugreek) seed powder
improves glucose homeostasis in alloxan diabetic rat
tissues by reversing the altered glycolytic, gluconeogenic
and lipogenic enzymes. Mol Cell Biochem 2001;224:45-
51.
16. Dixon RL, Hart LG, Rogers LA, Fouts JR. The
Metabolism of Drugs by Liver Microsomes from
Alloxan-Diabetic Rats: Long Term Diabetes. J Pharmacol
Exp Ther 1963;142:312-7.
17. El-Demerdash FM, Yousef MI, El-Naga NIA.
Biochemical study on the hypoglycemic effects of onion
and garlic in alloxan-induced diabetic rats. Food Chem
Toxicol 2005;43:57-63.
18. Maithili V, Dhanabal SP, Mahendran S, Vadivelan R.
Antidiabetic activity of ethanolic extract of tubers of
Dioscorea alata in alloxan induced diabetic rats. Indian J
Pharmacol 2011;43:455-9.
19. Pari L, Maheswari JU. Hypoglycaemic effect of Musa
sapientum L. in alloxan-induced diabetic rats. J
Ethnopharmacol 1999;68:321-5.
20. Dhandapani S, Subramanian VR, Rajagopal S,
Namasivayam N. Hyoplipidemic effect of cuminum
cyminum cyminum L. on alloxan- induced diabetic rats.
Pharmacol Res 2002;46:251-5.
21. Abdel-Barry JA, Abdel-Hassan IA, Al-Hakiem MHH.
Hypoglycaemic and antihyperglycaemic effects of
Trigonella foenum-graecum leaf in normal and alloxan
induced diabetic rats. J Ethnopharmacol 1997;58:149-55.
22. Karen. A Layman's Guide to Health, Medication Use,
Breeding, and Responsible Care of Pet Rats. Rat Health
Guide; 2020.
23. Christensen S, Kusano E, Yusufi A, Murayama N, Dousa
TP. Pathogenesis of nephrogenic diabetes insipidus due to
chronic administration of lithium in rats. J Clin Invest
1985;75:1869-79.
24. Lubar JF, Boyce BA, Schaefer CF. Etiology of polydipsia
and polyuria in rats with septal lesions. Physiol Behav
1968;3:289-92.
25. Hills A, Chalmers T, Webster G, Rosenthal O, Conover
H, Songster E. Adrenal cortical regulation of the
distribution of water and electrolytes in the human body. J
Clin Invest 1953;32:1236-47.
26. Groenendyk S, English P, Abetz I. External balance of
water and electrolytes in the horse. Equine Vet J
1988;20:189-93.
27. Darrow DC, Yannet H. Metabolic studies of the changes
in body electrolyte and distribution of body water induced
experimentally by deficit of extracellular electrolyte. The
J Clin Invest 1936;15:419-27.
28. Weisberg HF. Water, electrolyte and acid-base balance.
Philadelphia, Pennsylvania, United States: The Williams
& Wilkins; 1953.
29. Arun N, Nalini N. Efficacy of turmeric on blood sugar
and polyol pathway in diabetic albino rats. Plant Foods
Hum Nutr 2002;57:41-52.
30. Dehkordi SB, Sajedianfard J, Owji AA. The effect of
intra-cerebroventricular injection of insulin on the levels
of monoamines on the raphe magnus nucleus of nondiabetic and short-term diabetic rats in the formalin test.
Iran J Basic Med Sci 2019;22:915
31. Fitzsimons T, Le Magnen J. Eating as a regulatory control
of drinking in the rat. J Comp Physiol Psychol
1969;67:273-83.
32. Atcha Z, Rourke C, Neo AH, Goh CW, Lim JS, Aw C-C,
et al. Alternative method of oral dosing for rats. J Am
Assoc Lab Anim Sci 2010;49:335-4
| Files | ||
| Issue | Vol 61 No 2 (2023) | |
| Section | Study Protocol | |
| DOI | https://doi.org/10.18502/acta.v61i2.12531 | |
| Keywords | ||
| Diabetes Protocol Reduce Mortality Diabetes Establishment | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Rafieian-Kopaei M, Amini Khoei H, Rahimi-Madiseh M. Can the Mortality Rate be Reduced in the Diabetes Induction Model in Rats? A Protocol Study. Acta Med Iran. 2023;61(2):88-91.
