Side Effects of streptozocin: A Synthesis of Findings from 22 Studies

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Original Abstract of the Article

Major Research Findings

Streptozotocin is a widely used drug in diabetes research, but it is known to have various side effects. 17 reported that hyperbaric oxygen therapy increased blood glucose levels in diabetic rats and reduced the number of pancreatic beta cells. This suggests that hyperbaric oxygen therapy may enhance the toxicity of streptozotocin to beta cells.

22 reported that streptozotocin is directly toxic to the kidneys, making it difficult to distinguish between diabetic nephropathy and streptozotocin-induced kidney damage. This study suggests that phlorizin, an SGLT inhibitor, is effective in reducing the toxicity of streptozotocin to the kidneys.

15 describes a rat model of type 2 diabetes induced by streptozotocin and nicotinamide. This model is widely used in diabetes research because it is close to human type 2 diabetes. However, streptozotocin is toxic not only to pancreatic beta cells but also to other organs such as the kidneys and liver, so caution is needed when using this model.

14 reported that aged garlic extract (AGE) lowered blood glucose levels and exhibited antioxidant effects in streptozotocin-induced diabetic rats. However, further research is needed because AGE may also affect other organs, so it needs further research before being used as a diabetes drug.

6 reported that the anti-cancer drugs streptozotocin and floxuridine reduce the virulence of Staphylococcus aureus. This research suggests that streptozotocin may be effective not only as a diabetes drug but also as an infection drug.

Reasons for side effects

Streptozotocin acts as a DNA synthesis inhibitor and damages the DNA of various cells, including pancreatic beta cells, leading to side effects.

Common side effects

Increased blood glucose levels

Streptozotocin inhibits insulin secretion by destroying pancreatic beta cells, leading to increased blood glucose levels. 17 suggests that hyperbaric oxygen therapy may enhance the toxicity of streptozotocin to beta cells.

Kidney damage

Streptozotocin is directly toxic to the kidneys and can cause kidney dysfunction. 22 suggests that phlorizin, an SGLT inhibitor, is effective in reducing the toxicity of streptozotocin to the kidneys.

Liver damage

Streptozotocin can also be toxic to the liver and cause liver dysfunction. 20 reported that baicalein improved liver function in streptozotocin-induced type 2 diabetic rats.

Gastrointestinal disorders

Streptozotocin is also toxic to gastrointestinal cells and can cause symptoms such as nausea, vomiting, and loss of appetite. 22 reported that gastric dilatation induced by streptozotocin is caused by inhibition of desacyl ghrelin clearance.

Nervous system disorders

Streptozotocin can also be toxic to nervous system cells and cause neurological disorders. 11 reported that exercise reduced inflammation in the spinal cord of streptozotocin-induced type 1 diabetic rats and protected nerve function. Also, 10 reported that neramexane, an NMDA receptor antagonist, is effective in reducing pain caused by streptozotocin-induced diabetic neuropathy.

Other side effects

Streptozotocin can cause side effects such as leukopenia, thrombocytopenia, and anemia. 6 reported that streptozotocin and floxuridine are effective in treating Staphylococcus aureus infections, but these drugs affect blood cells and require caution.

Countermeasures for side effects

Increased blood glucose levels

Increased blood glucose levels can be controlled by administering insulin or using drugs that lower blood glucose levels.

Kidney damage

Kidney damage can be addressed by discontinuing streptozotocin administration or administering kidney protectants. 20 reported that baicalein improved kidney function in streptozotocin-induced type 2 diabetic rats.

Liver damage

Liver damage can be addressed by discontinuing streptozotocin administration or administering liver protectants. 20 reported that baicalein improved liver function in streptozotocin-induced type 2 diabetic rats, but rosiglitazone showed liver toxicity, so caution is needed.

Gastrointestinal disorders

Gastrointestinal disorders can be addressed by discontinuing streptozotocin administration or administering antiemetics or appetite stimulants.

Nervous system disorders

Nervous system disorders can be addressed by discontinuing streptozotocin administration or administering neuroprotectants. 11 reported that exercise reduced inflammation in the spinal cord of streptozotocin-induced type 1 diabetic rats and protected nerve function. Also, 10 reported that neramexane, an NMDA receptor antagonist, is effective in reducing pain caused by streptozotocin-induced diabetic neuropathy.

Comparison between studies

Commonalities in research

These studies indicate that streptozotocin is widely used in diabetes research, and its side effects are a concern. These studies also suggest various approaches to reducing the side effects of streptozotocin.

Differences in research

The severity and type of side effects of streptozotocin vary depending on the study. This is thought to be affected by various factors such as the dosage and administration method of streptozotocin, the animal species, and the experimental conditions. Approaches to reducing the side effects of streptozotocin also vary depending on the study.

Precautions for applying research to real life

Streptozotocin is widely used in diabetes research, but its use in humans is limited. Streptozotocin has a high risk of side effects in humans and is not used as a therapeutic drug. However, streptozotocin plays an important role in elucidating the pathogenesis of diabetes and developing therapeutic drugs. The results of animal experiments using streptozotocin provide valuable information for developing therapeutic drugs for humans.

Current research limitations

Research on the side effects of streptozotocin is still insufficient. In particular, there is a lack of data on the side effects of streptozotocin in humans. Also, effective methods for reducing the side effects of streptozotocin have not yet been established.

Future research directions

Further research is needed to reduce the side effects of streptozotocin. It is especially important to collect data on the side effects of streptozotocin in humans. Developing new drugs and treatments to reduce the side effects of streptozotocin is also an important challenge.

Conclusion

Streptozotocin is an important drug in diabetes research, but it is known to have various side effects. The risks of these side effects must be fully understood when using streptozotocin. It is hoped that future research on the side effects of streptozotocin will advance and make it possible to use streptozotocin more safely.

Literature analysis of 22 papers
Positive Content
20
Neutral Content
1
Negative Content
1
Article Type
0
0
0
2
22
1.

Long-term treatment with streptozocin/5-fluorouracil chemotherapy in patients with metastatic pancreatic neuroendocrine tumors: Case series.

Author: MüllerChristian, KreisslMichael C, KloseSilke, KrauseAndreas, KeitelVerena, VeneritoMarino

pNET treatment

This study discusses the current guidelines recommending a combination of streptozocin (STZ) and 5-fluorouracil (5-FU) for patients with metastatic well-differentiated pancreatic neuroendocrine tumors (pNETs) requiring systemic therapy.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

2.

A practical guide for induction of type-2 diabetes in rat: Incorporating a high-fat diet and streptozotocin.

Author: GheibiSevda, KashfiKhosrow, GhasemiAsghar

Diabetes prevention
Diabetes treatment
Side effects

This review describes a commonly used rat model of type 2 diabetes induced by a high-fat diet and streptozotocin. The model has advantages and disadvantages, and it is important to consider these when interpreting results.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

3.

Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy.

Author: AlomariGhada, Al-TradBahaa, HamdanSalehhuddin, AljabaliAlaa, Al-ZoubiMazhar, BatainehNesreen, QarJanti, TambuwalaMurtaza M

diabetic kidney disease
renal function improvement
no side effects

This study investigated the effects of 50-nm gold nanoparticles (AuNPs) on diabetic kidney disease in rats. AuNPs treatment prevented diabetes-associated hyperglycemia and ameliorated renal damage by reducing oxidative stress, inhibiting extracellular matrix accumulation, and improving podocyte function.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Pharmacodynamic interaction of cumin seeds (Cuminum cyminum L.) with glyburide in diabetes.

Author: KaurGinpreet, UpadhyayNidhi, TharappelLeo J Philip, InvallyMihir

Diabetes management

Cumin extract has anti-diabetic effects in streptozotocin-induced diabetic rats and can lower elevated glucose levels by more than 45% without causing hypoglycemia.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

6.

The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus.

Author: YeoWon-Sik, AryaRekha, KimKyeong Kyu, JeongHyunyoung, ChoKyu Hong, BaeTaeok

Anti-virulence
Staphylococcus aureus infection
DNA damage

Streptozotocin (STZ) and floxuridine (FU), two anti-cancer drugs, were identified as potential anti-virulence drug candidates against Staphylococcus aureus infection. FU was more efficient than STZ in repressing Sae-regulated promoters and protecting human neutrophils from S. aureus-mediated killing. Both compounds showed in vivo efficacy in murine models of infection without noticeable side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

Taraxerol as a possible therapeutic agent on memory impairments and Alzheimer's disease: Effects against scopolamine and streptozotocin-induced cognitive dysfunctions.

Author: BertéTalita Elisa, DalmagroAna Paula, ZimathPriscila Laiz, GonçalvesAna Elisa, Meyre-SilvaChristiane, BürgerCristiani, WeberCarla J, Dos SantosDiogo Adolfo, Cechinel-FilhoValdir, de SouzaMárcia M

AChE inhibition
Memory improvement

Taraxerol (TRX), a triterpene isolated from plants, exhibited AChE inhibitory activity and improved scopolamine- and STZ-induced memory impairment in animal models. This suggests its potential as a therapeutic agent for Alzheimer's disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

The Effects and Mechanism of Quercetin Dietary Supplementation in Streptozotocin-Induced Hyperglycemic Arbor Acre Broilers.

Author: YingLinlin, ChaudhryMaria Tabassum, XiaoFenglin, MaoYanjun, WangMi, WangBo, WangShanshan, LiYao

diabetes treatment

Dietary supplementation with quercetin, a flavonoid found in fruits and vegetables, was shown to have a protective effect in streptozotocin- (STZ-) induced hyperglycemic Arbor Acre (AA) broilers by decreasing oxidative stress and improving glucose metabolism.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

10.

Antinociceptive effects of chronic administration of uncompetitive NMDA receptor antagonists in a rat model of diabetic neuropathic pain.

Author: ChenShao-Rui, SamoriskiGary, PanHui-Lin

Minimal side effects
Neuropathic pain relief

Chronic administration of neramexane effectively attenuated diabetic neuropathic pain in rats, comparable to the effects of memantine and gabapentin.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Effect of exercise on neurogenic inflammation in spinal cord of Type 1 diabetic rats.

Author: ThakurVikram, GonzalezMayra, PenningtonKristen, NargisSyeda, ChattopadhyayMunmun

Alternative treatment for sensory neuropathy
Preserved sensory nerve function
Reduced inflammation in spinal cord

This study found that moderate exercise for 6 weeks reduced inflammation in the spinal cord of diabetic rats and preserved sensory nerve function. Exercise may be a valuable alternative treatment for diabetic neuropathy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Doxorubicin and streptozotocin after failed biotherapy of neuroendocrine tumors.

Author: PavelMarianne E, BaumUlrich, HahnEckhart G, HensenJohannes

Neuroendocrine tumor treatment

This study examines the potential benefits of chemotherapy in patients with well-differentiated neuroendocrine tumors who experience rapid tumor progression under biotherapy (somatostatin analogs and interferon-alpha).

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

13.

Metformin attenuates hyperalgesia and allodynia in rats with painful diabetic neuropathy induced by streptozotocin.

Author: MaJunxiong, YuHailong, LiuJun, ChenYu, WangQi, XiangLiangbi

Diabetic neuropathy treatment

Metformin can attenuate diabetes-induced hyperalgesia and allodynia in rats, possibly through its anti-oxidative effect via the AMPK pathway.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Anti-diabetic and anti-oxidant potential of aged garlic extract (AGE) in streptozotocin-induced diabetic rats.

Author: ThomsonMartha, Al-QattanKhaled K, JsDivya, AliMuslim

AGE
Anti-diabetic effects

This study investigated the anti-diabetic effects of aged garlic extract (AGE) in streptozotocin (STZ)-induced diabetic rats. Results showed that AGE significantly reduced blood glucose levels in diabetic rats, suggesting its potential benefits in managing diabetes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Streptozotocin-nicotinamide-induced rat model of type 2 diabetes (review).

Author: GhasemiAsghar, KhalifiS, JediS

Diabetes research
Streptozotocin/nicotinamide model
Type 2 diabetes model

This study provides an overview of the streptozotocin and nicotinamide-induced rat model of type 2 diabetes, a commonly used model in diabetes research. It highlights the model's advantages and disadvantages for studying diabetes in humans.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

17.

Enhancement of glucose toxicity by hyperbaric oxygen exposure in diabetic rats.

Author: MatsunamiTokio, SatoYukita, MorishimaTsunenori, ManoYoshihiro, YukawaMasayoshi

Beta-cell damage
Glucose increase

This study investigated the effects of hyperbaric oxygen (HBO) treatment on glucose homeostasis and pancreatic beta-cells in diabetic rats. Results showed that HBO exposure enhanced the cytotoxic effect of streptozotocin (STZ) on beta-cells, indicating that HBO should be cautiously used in diabetic patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Docking, synthesis and anti-diabetic activity of novel sulfonylhydrazone derivatives designed as PPAR-gamma agonists.

Author: Zapata-SudoGisele, LimaLídia M, PereiraSharlene L, TrachezMargarete M, da CostaFilipe P, SouzaBeatriz J, MonteiroCarlos E S, RomeiroNelilma C, D'AndreaÉverton D, SudoRoberto T, BarreiroEliezer J

Diabetic neuropathy treatment
Hypoglycemic activity

Diabetes is a metabolic disorder characterized by hyperglycemia. This study describes the virtual screening and synthesis of a novel series of sulfonylhydrazone derivatives designed as peroxisome proliferator-activated receptor gamma (PPARγ) agonists. These derivatives showed experimental affinity for PPARγ and were investigated for hypoglycemic activity in a murine model of diabetes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

Adverse effects of gabapentin and lack of anti-allodynic efficacy of amitriptyline in the streptozotocin model of painful diabetic neuropathy.

Author: LindnerMark D, BourinClotilde, ChenPing, McElroyJohn F, LeetJohn E, HoganJohn B, StockDavid A, MachetFrederic

Cognitive deficits
Motor/ambulatory deficits

Amitriptyline did not show anti-allodynic effects in a rat model of painful diabetic neuropathy, while gabapentin produced robust anti-allodynic effects but also significant motor and cognitive deficits.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

20.

Prophylactic effect of baicalein against renal dysfunction in type 2 diabetic rats.

Author: AhadAmjid, MujeebMohd, AhsanHaseeb, SiddiquiWaseem Ahmad

Diabetic nephropathy prevention
Liver toxicity

This study explored the protective effects of baicalein, a flavonoid, on diabetic nephropathy (DN) in rats. Baicalein significantly improved renal function and reduced inflammation compared to rosiglitazone, a standard antidiabetic drug. These findings suggest baicalein could be a promising treatment option for DN.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound healing effects and cytotoxicity/genotoxicity profile.

Author: BagdasDeniz, EtozBetul Cam, GulZulfiye, ZiyanokSedef, InanSevda, TuracozenOzge, GulNihal Yasar, TopalAyse, CinkilicNilufer, TasSibel, OzyigitMusa Ozgur, GurunMine Sibel

Accelerated wound healing
Improved blood glucose levels
Reduced oxidative stress
Cytotoxicity
Genotoxicity

This study investigated the effects of chlorogenic acid (CGA), a dietary antioxidant, on wound healing in diabetic rats. CGA was found to accelerate wound healing and decrease oxidative stress, but it also induced side effects such as cyto/genotoxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

22.

Phlorizin pretreatment reduces acute renal toxicity in a mouse model for diabetic nephropathy.

Author: BrouwersBas, PruniauVincent P E G, CauwelierElisa J G, SchuitFrans, LerutEvelyne, EctorsNadine, DeclercqJeroen, CreemersJohn W M

Diabetic nephropathy induction
Kidney toxicity

A new protocol for inducing diabetic nephropathy (DN) in mice using low doses of streptozotocin (STZ) with little or no toxic side effects has been developed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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