Kindly suggest the moderate dose of STZ to induce diabetes in Rattus norvegicus for evaluating antidiabetic activity of herbal plants. We administered STZ with sodium citrate buffer (4.5 pH) with a dosage of 35 mg/kg body weight of rat through i.p at single dose. But the fasting blood glucose level was increased >500 mg/dl on the 3rd day some rats (mostly male) were dead 5 days after i.p injection of STZ.
I assume you are trying to induce type 2 diabetes. We use 60% high fat diet for 6 weeks to induce obesity, after which we finally inject 35mg/kg STZ intravenously. Because this procedure generally carries the risk of mortality in the animals, there are suggestions that the use of fructose/sucrose in their drinking water for a few days after injection of STZ may prevent deaths.
You should follow mention below point to reduce the death:
1. Should take rats of 3 to 3.5 month old (weight around 250-300 gm)
2. Before induction should put rats on fasting 12-16 hrs.
3.After induction of diabetes should give the sucrose(15g/L) solution for 48 hrs.
3. If blood glucose very high then should give slow acting human insulin of 4-6 U/kg body wt of rats to maintain blood glucose nearly 300 to 350 mg/dL.
I think above point help you in your experiment.
You should take care during administration of STZ to prevent rupturing of tissue.
You can use the protocol of repeated administration of STZ whichprevent death.
The moderate dose would be 120mg/Kg body weight, if you want to administer only one time. If you want to administer every day, then you can even go to lower doses of 50-80mg/Kg body weight.
You may want to have a look at the conversation I have been having with Elavarasi S (also from Nehru memorial college) on the use of STZ. Above comments all very useful. Unfortunately one complication is the variable effect depending on rat strain, fasted or not, batch of STZ, how long since STZ made up. You need to work out and control these factors to use STZ reliably. You may get away without doing this or you may waste a lot of time and money. There are also of course single dose versus multiple dose protocols as discussed on here. The choice is yours! I use insulin to control BG as above.
I am completaly agreed with the previous comment. But it is important to have experience from previous studies with research hypothesis similar to yours. And from my experience it is better to have male rats if you can choose. 50% of female rats died after 4-7 days. I success to have hyperglycemia after one dosis of 60 mg/kg. But as I saw in other studies some researcher had a problem with duration of hyperglycemia because healthy part of pancreas cells hypertrophied. I had all symptoms of DM in three weeks that was duration of my study. I hope that this is useful to you.
65 mg/kg body weight, 1 x IP for model of model of type I diabetes. No deaths, confirmed diabetes (except 2 out of approximate 24 rats). Adult rats, approximate weight of 350 g were used. Be careful of how you perform IP injections. Poor placement is what might cause death.
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