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Effects of Allyl Isothiocyanate on Oxidative and Inflammatory Stress in Type 2 Diabetic Rats

2022, Okulicz, Monika, Hertig, Iwona, Król, Ewelina, Szkudelski, Tomasz

Oxidative stress and inflammation play a crucial role in the pathogenesis and progression of diabetes. Currently, there is a growing need to exploit plant-derived bioactive compounds to support conventional therapies. The purpose of this study was to explore allyl isothiocyanate (AITC) potency in reducing oxidative and inflammatory stress along with its profitable modulation trace element status in pathological conditions such as diabetes. Two weeks of oral AITC treatments (2.5, 5, and 25 mg/kg body weight per day) were evaluated in Wistar rats with diabetes induced by a high-fat diet and streptozotocin. The study included AITC influence on antioxidant factors (SOD, CAT, GST, Nrf2), stress and inflammatory markers (cortisol, CRP, IL-1β, IL-6, TNFα, NF-κB), lipid peroxidation indices (TBARS, -SH groups), and trace element status (Fe, Zn, and Cu) in the detoxification and lymphoid organs. Independently of dose, AITC increased cortisol levels in rat blood serum and decreased total thiol groups (T-SH) and protein-bound thiol groups (PB-SH) collaterally with raised thiobarbituric acid reactive substances (TBARS) in diabetic rat liver. The inflammation and oxidative effects were enhanced by an AITC dose increase. The highest dose of AITC, 25 mg/kg b.w., strongly affected the inflammation process by increasing IL-6, IL-1β, and TNFα in the blood serum, and it upregulated Nrf2 transcription factor with increased SOD, GPx, and GST activities in the liver. AITC showed an equivocal effect on profitable modulation of disturbances in mineral homeostasis in the liver, kidney, and spleen. Our findings revealed that two-week AITC treatment exacerbated oxidative and inflammation status in diabetic rats.

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Quercetin as an Anti-Diabetic Agent in Rodents—Is It Worth Testing in Humans?

2025, Szkudelski, Tomasz, Szkudelska, Katarzyna, Łangowska, Aleksandra

Quercetin is a biologically active flavonoid compound that exerts numerous beneficial effects in humans and animals, including anti-diabetic activity. Its action has been explored in rodent models of type 1 and type 2 diabetes. It was revealed that quercetin mitigated diabetes-related hormonal and metabolic disorders and reduced oxidative and inflammatory stress. Its anti-diabetic effects were associated with advantageous changes in the relevant enzymes and signaling molecules. Quercetin positively affected, among others, superoxide dismutase, catalase, glutathione peroxidase, glucose transporter-2, glucokinase, glucose-6-phosphatase, glycogen phosphorylase, glycogen synthase, glycogen synthase kinase-3β, phosphoenolpyruvate carboxykinase, silent information regulator-1, sterol regulatory element-binding protein-1, insulin receptor substrate 1, phosphoinositide 3-kinase, and protein kinase B. The available data support the conclusion that the action of quercetin was pleiotropic since it alleviates a wide range of diabetes-related disorders. Moreover, no side effects were observed during treatment with quercetin in rodents. Given that human diabetes affects a large part of the population worldwide, the results of animal studies encourage clinical trials to evaluate the potential of quercetin as an adjunct to pharmacological therapies.

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Differentiated Effects of Allyl Isothiocyanate in Diabetic Rats: From Toxic to Beneficial Action

2022, Okulicz, Monika, Hertig, Iwona, Szkudelski, Tomasz

Allyl isothiocyanate (AITC), a constituent of Brassica family plants, has been reported to possess a high bioactivity in animal and human cells, showing ambiguous properties from adverse to beneficial ones. It was reported its genotoxic, carcinogenic, goitrogenic effects. On the other side, AITC has shown anti-cancer, cardioprotective, neuroprotective, and lately anti-obesity abilities. So far, its anti-diabetic effects are poorly explored. We tried to assess AITC action on carbohydrate, lipid and hormonal disorders in high fat diet-fed/streptozotocin diabetic rats. In this report, diabetic rats were treated intragastrically at doses 2.5, 5 and 25 mg/kg b.w./day of AITC for 2 weeks. Irrespectively of doses, AITC considerably lowered thyroid hormones (fT4, fT3), increased liver TG content, and also caused robust LDL-cholesterol and direct bilirubin concentration enhancement. Moreover, AITC at the highest dose caused pancreatic amylase and lipase drops and thyroid gland hypertrophy. AITC at 2.5 and 5 mg significantly reduced blood glucose levels along with robust beta-hydroxybutyric acid drop. Additionally, AITC at 5 mg improved insulin sensitivity (HOMA-IR index) in spite of reduced blood insulin. To conclude, despite amelioration of diabetic hyperglycemia by AITC, the adverse lipids and hormonal effects may exclude its use as a health-promoting compound in terms of anti-diabetic properties.