Streptozotocin, derived from a fermentation broth of Streptomyces achromogenes, was first isolated as a new antibiotic in 1956, which had a significant antimicrobial action for a wide spectrum of organisms [1].
In 1960 and 1961, antitumor activity screening at both Upjohn Research Laboratories and contract laboratories of the National Cancer Institute demonstrated antitumor effect, particularly in L1210 leukemia [2].
Murine tumor studies led to the discovery that STZ produced hyperglycemia [3], and further toxicology studies in dogs and rhesus monkeys demonstrated that STZ had a potent diabetogenic effect [4].
Ever since then, STZ has been used as a diabetogenic agent in experimental animals.
The mechanisms of STZ-induced hyperglycemia are considered as follows: (1) STZ causes DNA strand breaks in pancreatic islets and stimulates nuclear poly(ADP- ribose) synthetase, and thus depletes the intracellular NAD+ and NADP+ levels, which inhibit proinsulin synthesis and induces diabetes [5]; (2) activated oxygen species, such as superoxide (O2 •- ), hydrogen peroxide (H2O2), hydroxyl radical (•OH) and singlet oxygen (1O2), have been implicated to play important roles in diabetes, especially diabetic angiopathy [6].
Most recent research demonstrated that intracerebroventricular injection of STZ in rats produces oxidative stress in brain to cause cognitive impairment in rats and is likened to sporadic Alzheimer’s disease (AD) in humans.
This paper will focus mainly on reviewing the free radicals generated by STZ and the related animal models of STZ-induced diseases.