Increasing evidence in both experimental and clinical studies suggests that oxidative stress is involved in the pathogenesis and progression of diabetic tissue damage. This study investigated the protective effects of quercetin treatment on oxidative stress, nuclear factor (NF)-kappaB activation and expression of inducible nitric oxide synthase (iNOS) in streptozotocin-induced diabetic rats. Male Wistar rats were divided into 4 groups: control rats, control rats treated daily with quercetin (150 micromol/kg, i.p.), untreated diabetic rats, and diabetic rats treated with quercetin. Diabetes was induced by a single i.p. injection of streptozotocin (70 mg/kg). Eight weeks later we measured TBARS and hydroperoxide-initiated chemiluminescence (QL) in liver as markers of oxidative stress, and activities of the antioxidant enzymes catalase, superoxide dismutase (SOD), and glutathione peroxidase, NF-kappaB activation by an electrophoretic mobility shift assay and expression of IkappaB kinases (IKKalpha and IKKbeta), the inhibitor IkappaB (IkappaBalpha and IkappaBbeta), and iNOS by Western blot. The plasma glucose concentration was significantly increased in diabetic rats and was not changed by quercetin. Streptozotocin administration induced significant increases in hepatic TBARS concentration, QL, and SOD and catalase activities that were prevented by quercetin. Activation of NF-kappaB, induction of IKKalpha and iNOS protein levels, and increased degradation of IkappaBalpha were also observed in streptozotocin-treated rats. All of those effects were abolished by quercetin. These findings suggest that quercetin treatment, by abolishing the IKK/NF-kappaB signal transduction pathway, may block the production of noxious mediators involved in the development of early diabetes tissue injury and in the evolution of late complications.

Quercetin Decreases Oxidative Stress, NF-κB Activation, and iNOS Overexpression in Liver of Streptozotocin-Induced Diabetic Rats

Antioxidant and pancreas-protective effect of aucubin on rats with streptozotocin-induced diabetes.

Introduction: The depletion of defensive body chemicals called antioxidants may increase the risk of complications from the most common form of diabetes mellitus. This study aims to evaluate blood serum lipid peroxidation product (malondialdehyde), an antioxidant, in non-insulin dependent male and female type 2 diabetic patients. Methods: Blood serum samples were collected from the diabetic patients and non-diabetic healthy controls. Malondialdehyde (MDA) level, which is an index of endogenous lipid peroxidation, reduced glutathione and protein content of the serum were estimated. Results: A significant elevation in MDA level and decrease in glutathione and protein content was observed in both male and female diabetic patients in comparison to non-diabetic controls. Conclusion: Our findings indicate that the increase in the lipid peroxidation product MDA and decline in glutathione-dependent antioxidant defences may appear early in non-insulin dependent type 2 diabetes mellitus patients before the development of secondary complications.

Serum lipid peroxidation and antioxidant enzyme levels in male and female diabetic patients.

Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. The aim of this study was to investigate the effect of different phosphodiesterase inhibitors on lipid peroxidation and total antioxidant capacity (TAC) of plasma in streptozotocin-induced diabetic rats (Rattus norvegicus). Rats became diabetic by a single administration of streptozotocin (STZ, 45 mg/kg). The effects of 15-days treatment by milrinone, sildenafil, and theophylline as cyclic-AMP and -GMP phosphodiesterase inhibitors (PDEIs) on diabetes-induced oxidative stress were studied. The levels of glucose, malonedialdehyde (MDA) the by product of lipid peroxides, and TAC (FRAP test) were estimated in plasma of control and experimental groups of rats. A significant increase in the levels of plasma glucose, and MDA and a concomitant decrease in the levels of TAC were observed in diabetic rats. These alterations were reverted back to near normal level after the treatment with PDEIs. Treatment of diabetic rats by PDEIs reduced MDA levels and increased TAC in the order of milrinone > sildenafil > theophylline. In conclusion, the present investigation show that PDIS possesses antioxidant activities, which may be attributed to their enhancing effect on cellular cyclic nucleotides contributing to the protection against oxidative stress in streptozotocin-induced diabetes. Exact mechanism of protective actions of cAMP- and cGMP-phosphodiesterase remains to be elucidated by further studies. This finding may suggest a place for PDEIs in maintaining health in diabetes.

Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats.

Antioxidant effects of Gongronema latifolium in hepatocytes of rat models of non-insulin dependent diabetes mellitus

The effect of dietary treatment on erythrocyte lipid peroxidation, superoxide dismutase, glutathione peroxidase, and serum lipid peroxidation in patients with type 2 diabetes mellitus.

Abstract We report the radioprotective attitude of Annona muricata (AM) leaf extract as antioxidant material to prevent cellular damage in the ileum tissue. The protective effects of an ethyl acetate extract of AM leaves are comprehensively investigated against radiation-induced ileal damage in numerous rats. Thirty-two adult female rats were separated into 4 groups (3 intervention groups and 1 control) as follows: controls received 0.01 mL/kg distilled water, the AM group received 300 mg/kg AM leaf extract, the ionizing radiation (IR) group received a single dose of whole body radiation (8.3 Gy) after 0.01 mL/kg saline treatment, and the AM + IR group received 300 mg/kg AM leaf extract treatment and were subjected to whole body radiation (8.3 Gy) 1 h after the last gavage. All treatments are administered by oral gavage once a day for 9 days. At the end of the experiment, biochemical total oxidant status (TOS, interleukin-6, and caspase) and histological examinations are performed on blood samples as well as ileum tissue. TOS levels are found to be significantly high in rats, which received irradiation, and those in the AM group when compared to controls. These findings suggest that AM has radioprotective effects on ileum tissue, likely because of its antioxidative properties. The findings of this research may contribute to the minimizing of major side effects induced by excessive radiation exposure in patients undergoing radiotherapy and may serve as a significant impetus for further assessments. However, future studies are highly recommended to confirm safety and to determine extraction technique and dosage before human use can be considered.

Clinical comprehensive and experimental assessment of the radioprotective effect of Annona muricata leaf extract to prevent cellular damage in the ileum tissue

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities. However, the impact of COVID-19 on long-term health outcomes remains to be elucidated. Aims: The Precision Medicine for more Oxygen (P4O2) consortium COVID-19 extension aims to identify long COVID patients that are at risk for developing chronic lung disease and furthermore, to identify treatable traits and innovative personalized therapeutic strategies for prevention and treatment. This study aims to describe the study design and first results of the P4O2 COVID-19 cohort. Methods: The P4O2 COVID-19 study is a prospective multicenter cohort study that includes nested personalized counseling intervention trial. Patients, aged 40–65 years, were recruited from outpatient post-COVID clinics from five hospitals in The Netherlands. During study visits at 3–6 and 12–18 months post-COVID-19, data from medical records, pulmonary function tests, chest computed tomography scans and biological samples were collected and questionnaires were administered. Furthermore, exposome data was collected at the patient’s home and state-of-the-art imaging techniques as well as multi-omics analyses will be performed on collected data. Results: 95 long COVID patients were enrolled between May 2021 and September 2022. The current study showed persistence of clinical symptoms and signs of pulmonary function test/radiological abnormalities in post-COVID patients at 3–6 months post-COVID. The most commonly reported symptoms included respiratory symptoms (78.9%), neurological symptoms (68.4%) and fatigue (67.4%). Female sex and infection with the Delta, compared with the Beta, SARS-CoV-2 variant were significantly associated with more persisting symptom categories. Conclusions: The P4O2 COVID-19 study contributes to our understanding of the long-term health impacts of COVID-19. Furthermore, P4O2 COVID-19 can lead to the identification of different phenotypes of long COVID patients, for example those that are at risk for developing chronic lung disease. Understanding the mechanisms behind the different phenotypes and identifying these patients at an early stage can help to develop and optimize prevention and treatment strategies.

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Havva Sahin

Papers

The effect of dietary treatment on erythrocyte lipid peroxidation, superoxide dismutase, glutathione peroxidase, and serum lipid peroxidation in patients with type 2 diabetes mellitus.

Clinical comprehensive and experimental assessment of the radioprotective effect of Annona muricata leaf extract to prevent cellular damage in the ileum tissue

Precision Medicine for More Oxygen (P4O2)—Study Design and First Results of the Long COVID-19 Extension