Disease relevance of STREPTOZOTOCIN

• Toxicity tests revealed that STZ and MNU were not toxic at equimolar concentrations [1].
• At 16 weeks after STZ injection, the score of lens opacity was more than 3 (diffuse central opacities) in diabetic placebo control rats, whereas it was less than 2 (peripheral vesicles and cortical opacities) and the lenses remained clear in animals treated with 0.3% of FR74366 [2].
• Daily treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia [3].
• Rats treated with streptozotocin (STZ) during the neonatal period have been used as a model of non-insulin-dependent diabetes mellitus [4].
• We conclude that iNOS-derived NO modulates glomerulosclerosis and tubulointerstitial fibrosis in chronic STZ nephropathy [5].

High impact information on STREPTOZOTOCIN

• In addition, eNOS protein expression, cavernosal constitutive NOS activity, and cGMP levels were reduced in the STZ-diabetic penis [6].
• RhoA/Rho-kinase protein abundance and MYPT-1 phosphorylation at Thr-696 were elevated in the STZ-diabetic rat penis [6].
• STZ-diabetic rats transfected with AAVCMVT19NRhoA had a reduction in RhoA/Rho-kinase and MYPT-1 phosphorylation at a time when cavernosal eNOS protein, constitutive NOS activity, and cGMP levels were restored to levels found in the control rats [6].
• In STZ-induced diabetic rats, beta II isoenzyme is preferentially increased in both aorta and heart, whereas PKC alpha did not change significantly [7].
• The increases in membranous PKC specific activity and DAG level are observed in both spontaneous diabetes-prone diabetic BB rats as well as in STZ-induced diabetic BB and Sprague-Dawley rats, which persisted for up to 5 weeks [7].

Chemical compound and disease context of STREPTOZOTOCIN

• Regardless of the route of cisplatin injection, both renal cortex platinum level and renal toxicity as quantified by blood urea nitrogen (BUN) increase, were significantly lower in STZ diabetic versus nondiabetic rats [8].
• After 4-weeks of STZ injection, diabetic rats exhibited a significant thermal hyperalgesia and cold allodynia along with increased plasma glucose and decreased body weights as compared with controls rats [9].

Biological context of STREPTOZOTOCIN

• STZ-induced diabetes (group III) caused a 57% reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60% increase in conjugated dienes [10].
• These findings suggest that factors in addition to the activation of poly(ADP-ribose) synthetase must be responsible for the toxicity seen with STZ, because MNU at a nonlethal concentration is capable of causing comparable DNA damage [1].
• Using the streptozotocin (STZ) diabetic rat as a model, the experiments in this study examined the effect of the diabetic state on bioavailability, renal accumulation and renal toxicity following intraperitoneal (i.p.) and intravenous (i.v.) injection of cisplatin at various doses [8].
• In three other groups of mice-db/db (B6.Cg-m+/+Lepr(db)/J) Type II diabetic (DM2) mouse, db/m (its heterozygote), and the corresponding wild type (WT)-TF [NO] was also much higher than in the rat, and unlike the B6129G2/J STZ diabetic mouse, did not change after the onset of diabetes [11].
• Using bromodeoxyuridine (BrdU) to label newly generated cells, a strong reduction in cell proliferation was obtained in DG and SVZ of mice sacrificed 20 days after STZ administration [12].

Anatomical context of STREPTOZOTOCIN

• After 2 weeks of diabetes without treatment, the normalization of blood glucose levels for up to 3 weeks with islet cell transplants in STZ-induced diabetic BB rats reversed the biochemical changes only in the heart, but not in the aorta [7].
• These results suggest that NO-induced internucleosomal DNA cleavage is an important initial step in the destruction and dysfunction of pancreatic beta-cells induced by inflammatory stimulation or treatment with STZ [13].
• Decreased myo-inositol content and Na+-K+-ATPase activity in superior cervical ganglion of STZ-diabetic rat and prevention by aldose reductase inhibition [14].
• Granulocyte macrophage-colony stimulating factor (GM-CSF) recruits immune cells to the pancreas and delays STZ-induced diabetes [15].
• Stress did not modulate nNOS expression, while nNOS mRNA and protein levels were significantly decreased in the hippocampus of STZ diabetic rats [16].

Associations of STREPTOZOTOCIN with other chemical compounds

• Male Sprague-Dawley rats were injected with streptozotocin (STZ, 65 mg/kg i.v.) and received insulin via ip osmotic minipumps (3 U/kg per day) [17].
• To characterize the role of the kallikrein-kinin system in diabetic cardiopathy, we studied the effect of streptozotocin (STZ) on the regulation of the myocardial bradykinin (BK) receptors, the B1 and B2 type, and two tissue kallikrein genes, rat kallikrein 1 (rKLK1) and rKLK7, in severely hyperglycemic rats [18].
• Increases in hypothalamic corticotrophin-releasing hormone (CRH) and inhibitory hippocampal mineralocorticoid receptor (MR) mRNA with STZ diabetes were not restored with either insulin or phloridzin treatments [19].
• In conclusion, overexpression of eNOS and cGMP in combination with sildenafil significantly increased both the peak ICP and total ICP to CNS in the STZ-diabetic rat, which was similar to the response observed in control rats [20].
• Male Fischer 344 (F344) rats were injected with 32 mg/kg STZ (i.p.) or citrate buffer [21].

Gene context of STREPTOZOTOCIN

• Thus, the B1 receptor does not play a regulatory role in either the healthy or in STZ-diabetic heart [18].
• We investigated the role of NO produced by inducible nitric oxide synthase (iNOS) in chronic STZ diabetic nephropathy [5].
• While iNOS protein was undetectable in any of the kidney specimens obtained from either strain, eNOS was present throughout the course of chronic STZ diabetes [5].
• The heterologous half-life of DBH in STZ-diabetic rats is significantly increased compared with that of control animals [22].
• In STZ kidneys treated with superoxide dismutase (SOD, 150 U/mL), afferent and efferent arteriolar L-NNA responses were restored to levels comparable to those of SOD-treated and untreated sham kidneys [17].

Analytical, diagnostic and therapeutic context of STREPTOZOTOCIN

• Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats [23].
• METHODS: We assayed NO synthase (NOS) activity by monitoring the conversion of L-[(14)C] arginine to L-[(14 )C] citrulline, identified the NOS isoforms by immunoblotting, and examined the effects of STZ-induced diabetes on NOS in the rat choroid [24].
• We have previously shown that dose-response studies performed in streptozotocin (STZ)-diabetic nude mouse recipients bearing established, functioning islet xenografts can be used to directly compare in vivo STZ-sensitivity between donor species and that tilapia (fish) islet grafts are exceedingly STZ-resistant [25].
• Moreover, the total erectile response was greater in STZ-diabetic rats receiving eNOS gene therapy plus sildenafil than STZ-rats receiving sildenafil or eNOS gene therapy alone [20].
• Male lean mice belonging to the obese-hyperglycemic strain were made diabetic by intravenous injection of streptozoticin [26].

References