Streptozotocin is a drug, which is also a carcinogen. Besides the pancreas, can it harm other vital organs? Are there any results related to this topic?
Well the possibility exist that it can affect other organs, what makes the pancreas the target for STZ is the presences of GLUT-2 receptors in relatively large amounts compare to the liver, kidney, brain, adipose tissue and skeletal muscle. So even though it is a strong alkalating carcinogen its activity is most specific in tissue with GLUT-2 receptors. I hope this answer the question.
STZ damages many organs in a dose dependent manner as dictated by GLUT-2 as above. This makes dose titration essential as overdosing will be fatal. Unfortunately the window you are aiming for is small with many variables affecting the effects of STZ as discussed in numerous other posts.
Yes it mainly affects pancreas, but
Different mechanisms of action on the beta cells destruction by STZ have been proposed. STZ is taken up by pancreatic β-cells via, glucose transporter GLUT 2 which is mainly expressed in pancreas
The main action is through free radical generation and proposed site for the action of STZ is the nuclear DNA. During decomposition of STZ, highly reactive carbonium ions are formed, which cause alkylation of DNA base (LeDoux et al., 1986). Recent experiments have also proved that the main reason for STZ induced β-cell death is alkylation of DNA (DeLaney et al., 1995; Elsner et al., 2000). The alkylating activity of STZ is related to its nitrosourea moiety, especially at the O6 position of guanine. After STZ injection to rats different methylated purines were found in tissues of these animals (Bennet and Pegg, 1981).
In the following phase of excision DNA repair, the nuclear enzyme poly (ADP-ribose) synthetase becomes activated to such an extent that cellular levels of its substrate NAD becomes critically depleted, leading to cell death (Heller, 1994). This process leads to depletion of cellular NAD+, further reduction of the ATP content and subsequent inhibition of insulin synthesis and secretion (Nukatsuka et al., 1990b). It was found that 3-aminobenzamide, a strong inhibitor of poly (ADP-ribose) synthase, protected against the action of STZ in rats, even when this substance was administered 45-60 min after STZ (Masiello et al., 1985).
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