[Indian Journal of Pharmacology (1994): (26), 225-226]

Alloxan-induced Diabetes in Rabbits and Effect of a Herbal Formulation D-400

Dubey, G.P., Dixit, S.P. and Alok Singh Department of Basic Principles, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

SUMMARY: Adult male rabbits injected with alloxan (50 mg/kg i. p.) were divided into two groups of nine each. One group received placebo and the other group an aqueous suspension of D-400, at the dose of 1 gm/kg body weight orally daily for 36 weeks. Blood glucose, blood urea and serum creatinine were estimated initially and at every 6-weekly intervals. At the end of 36 weeks D-400 significantly prevented the rise in blood urea and serum creatinine levels as compared to the control. Although a rise in blood sugar was noticed in both the groups, the level of blood sugar after 36 weeks was significantly lower in the D-400 treated group. This shows the favourable response of D-400 against alloxan-induced renal damage and hyper glycaemia. Key words: D-400; alloxan diabetes; renal damage; rabbits Diabetic nephropathy is one of the major complications of non-insulin dependent diabetes mellitus (NIDDM) which is a common cause of death in diabetic patients1. The severity of renal disease in diabetic patients correlates with the levels of blood urea and serum creatinine. Diabetic nephropathy accounts for considerably morbidity and mortality even in patients with well controlled blood sugar values2. Many indigenous drugs have been reported to lower blood sugar levels in diabetic individuals3,4. D-400 is one such indigenous drug combination which has been studied for its effect on blood sugar levels5. The main ingredients of D-400 are Eugenia jambulana, Pterocarpus marsupium, Ficus glomerulata and Ocimum sanctum in addition to other herbs, which have blood sugar lowering effect. While the effect of D-400 on blood sugar has been studied5, no studies have been conducted regarding the effects on renal impairment in diabetic nephropathy. In the present experiment, D-400 has been tried in alloxan-induced diabetes and renal damage in rabbits and the effect on blood glucose, blood urea and serum creatinine has been studied. MATERIALS AND METHODS Eighteen adult male rabbits were selected for the study. The rabbits weighed on an average 1 kg and all of them were given alloxan (50 mg/kg, i.p.) after a baseline blood urea, serum creatinine and blood sugar estimation was done. (alloxan in low doses, produces an NIDDM

like state, which can progress to a gradual recovery or to an insulin dependent stage)6,7. The rabbits were divided into two groups of 9 each. One group received D-400 at the dose of 1 gm/kg body weight and the other received normal saline. The dosage of 1 gm/kg of D-400 was arrived at, based on previous experimental trials of 0.5, 1.0 and 1.5 gms/kg. The biochemical parameters were checked once in 6 weeks for 36 weeks. A comparative analysis was done after the study was concluded. Statistical analysis was done by student's `t' test. RESULTS A rise in blood sugar starting one week after alloxan injection followed by a spontaneous and gradual fall was noted in all 18 rabbits. Blood urea and serum creatinine levels showed significant rise in both groups indicating renal damage caused by alloxan. At the end of 36 weeks, blood sugar, urea and serum creatinine levels were significantly lower in the D-400 treated group as compared to the control (Table 1).

Table 1: Changes in blood glucose, blood urea and serum creatinine in alloxan-induced diabetic nephropathy in rabbits Parameters Blood glucose (mg%) Blood urea (mg%) Serum creatinine (mg%) Initial value C 41.50 ±3.30 19.67 ±2.66 0.74 ±0.10 T 47.17 ±4.45 21.67 ±2.66 0.94 ±0.20 After 1 week C 169.33 ±7.78 20.50 ±1.61 0.73 ±0.10 T 184.00 ±8.41 21.83 ±1.51 0.95 ±0.20 6 weeks C 133.67 ±3.79 34.50 ±8.48 1.47 ±0.17 T 127.33 ±5.07 28.33 ±1.85 1.07 ±0.17 12 weeks C 121.00 ±3.42 45.17 ±2.55 2.27 ±0.24 T 115.33 ±4.51 33.67 ±2.08 1.29 ±0.20 24 weeks C 115.67 ±2.54 49.67 ±5.50 2.57 ±1.24 T 97.67 ±3.85 35.67 ±2.28 1.32 ±0.20 36 weeks C 111.00 ±5.13 56.67 ±2.20 2.90 ±0.41 T 56.33* ±4.78 29.33* ±3.44 1.30* ±0.20

*p<0.001 compared to control. C=Control, T=Treated

DISCUSSION Many oral hypoglycemic agents are normally metabolised or cleared by the kidneys and so accumulate in uraemic patients thus increasing the risk of hypoglycaemia and toxicity8,9. In addition to this, these drugs are also associated with long term complications. In the present study D-400 a herbomineral preparation has shown significant hypoglycaemic action and proved to be effective on alloxan-induced nephrotoxicity. It is very difficult to mention which of the ingredients was responsible for this favourable response. According to Ayurvedic texts, a combination of substances is used to get the enhanced desired action and eliminate unwanted side effects10,11. These ingredients may aid absorption of active principles responsible for hypoglycaemic action and protective action on kidneys. Since small number of animals were used in the present study, some more experimental and clinical trials should be conducted to evaluate the efficacy of this drug on diabetic complications. REFERENCES 1. Deekert T, Grenfel A. Epidemiology and natural history of diabetic nephropathy, In: Pickup JC, Williams G. eds. Textbook of Diabetes . London: Black well Scientific Publications, 1991: Vol. 2, 64: 651-6.


Grenfel A. Clinical features and management of established diabetic nephropathy. In: Pickup JC, Williams G. eds. Textbook of Diabetes. London: Black Well Scientific Publications, 1991: Vol.2, 67: 677-97. Ajgaonkar SS. Ancient Indian Medicines and diabetes mellitus. In: Bajaj JS. ed. Diabetes mellitus in developing countries, New Delhi. All India Medical Sciences, Mehta Offset Works, 1984:3-10. Upadhyay VP, Pandey K. Ayurvedic approach to diabetes mellitus and its management by indigenous resources. In: Bajaj JS ed. Diabetes mellitus in developing countries. All India Medical Sciences, 1984:375-7. Dubey GP, Aruna Agarwal, Alok Singh. Evaluation of D-400, an indigenous herbal preparation, in diabetes mellitus. Indian J Int Med 1993:3: 183-6. Bailey C J, Flatt PR. Animal models in non-insulin dependent diabetes mellitus. Oxford London, Blackwell Scientific Publications, 1991, 235. Cooperstein S.J. Watkins D. Action of toxic drugs on islet cells in: Cooperstein SJ, Watkin D, ech. The islets of Langerhans. New York; Academic Press, 1981:387-42. Borch-Johnsen K. Andersen PK, Deckert T. The effect of proteinuria on relative mortality in Type 1 (insulin-dependant) diabetes mellitus. Diabetologia 1985: 28-590-6. Grenfell A, Watkins PJ. Clinical diabetic nephropathy. Natural history and complications. Clin Endocrinol Metab 1986; 15: 783-805. Satyavati GV, Gupta AK, Tandon N. Medicinal plants of India. Vol. 1 & 2, New Delhi: Indian council of Medical Research, 1987. Nadkarni AK, Materia Medica 3rd ed. Vol. 1, Bombay: Popular Prakashan, 1982:516-8.



5. 6. 7. 8. 9. 10. 11.



3 pages

Report File (DMCA)

Our content is added by our users. We aim to remove reported files within 1 working day. Please use this link to notify us:

Report this file as copyright or inappropriate