Reduced Insulin Resistance and Oxidative Stress in a Mouse Model of Metabolic Syndrome following Twelve Weeks of Citrus Bioflavonoid Hesperidin Supplementation: A Dose-Response Study.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice (p < 0.0001). Fasting blood glucose (FBG) increased by 40% (p < 0.0001), plasma insulin by 100% (p < 0.05), and HOMA-IR by 150% (p < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day (p < 0.0001) and 50% at 280 mg/kg/day (p < 0.005). HOMA-IR decreased by 45% at both doses (p < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups (p < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice (p < 0.001) and reduced by 20% with all hesperidin doses (p < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.

A systematic review exploring the mechanisms by which citrus bioflavonoid supplementation benefits blood glucose levels and metabolic complications in type 2 diabetes mellitus.

BACKGROUND: Citrus bioflavonoids are polyphenolic compounds that are derived from citrus fruits and vegetables. Although they are well known for their powerful antioxidant properties, their effects on glycemic control are not well understood. This review aims to highlight the potential benefits of using citrus bioflavonoids in patients with type 2 diabetes mellitus and its metabolic complications, as well as the medicinal effects of known subclasses of naturally occurring citrus bioflavonoids. METHODS: In this systematic review, a survey of studies was conducted from January 2012 to February 2023 using various databases (PubMed, Medline, Google Scholar, and Scopus) to determine the effects of citrus bioflavonoid supplementation on reducing oxidative stress, improving lipid profiles, and glycemic index in patients with diabetes mellitus, as well as the proposed mechanisms of action. RESULTS: The results of the survey indicate that citrus bioflavonoids may have a positive impact on reducing oxidative stress levels in patients with type 2 diabetes mellitus. In addition to reducing oxidative stress, citrus bioflavonoids may also have a positive impact on other markers of diabetes. For example, studies have shown that they can reduce non-enzymatic protein glycation, which is a process that occurs when glucose molecules bind to proteins in the body. CONCLUSION: The reduction in oxidative stress that can be achieved using citrus bioflavonoids may help to maintain antioxidant levels in the body, thereby reducing the severity of diabetes and its complications. These findings suggest that citrus bioflavonoids may be a useful complementary therapy for patients with diabetes.

Oridonin supplementation in rabbits may help to improve the outcome of induced atherosclerosis via autophagy induction.

BACKGROUND AND AIM: Inflammation plays a crucial role in the development of atherosclerotic plague. Oridonin is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens. It is a natural terpenoids that is known as a strong anti-inflammatory supplement by acting as a potent inhibitor of the TXNIP/NLRP3 pathway. Hence, it can reduce the severity of inflammation and improve the outcome of atherosclerotic changes. This study aims to evaluate the anti-inflammatory effects of oridonin in the progression of atherosclerotic plague in rabbits. METHODS: Sixty-three male rabbits were included. The rabbits were randomly assigned to one of the three study groups (21 rabbits in each group), normal control diet (NC) fed normal diet for 8 weeks, atherogenic control (AC) fed atherogenic diet (2% cholesterol-enriched diet) for 8 weeks, and oridonin treated group (OT) fed atherogenic diet (2% cholesterol-enriched diet) with oridonin (purity 94%, Sigma-Aldrich, USA) at 20 mg/kg orally daily for 8 weeks. After the end of the study, blood and tissue samples were collected for analysis of various markers of inflammation and atherosclerotic plaque progression. RESULTS: Serum lipids showed a statistically significant improvement in terms of reduction in total cholesterol and low-density lipoprotein (LDL) in the OT group compared to the AC group. This was associated with a significant reduction in serum F2-isoprostane (marker of inflammation) and LC3B (marker of tissue autophagy) between the OT group compared to the AC group. There was also a significant reduction in NLRP3 inflammasome RNA expression in OT group, P<0.001. CONCLUSIONS: In animal model, with atherogenic diet, oridonin supplementation can significantly improve the outcome of atherosclerosis by its strong anti-inflammatory action.

‘Look, wait, I’ll translate’: refugee women’s experiences with interpreters in healthcare in Aotearoa New Zealand.

This study aimed to explore refugee women's experiences of interpreters in healthcare in Aotearoa, New Zealand (NZ). Semi-structured interviews were conducted with nine women who arrived in NZ as refugees. Analysis involved a 'text in context' approach. An iterative and interpretive process was employed by engaging with participant accounts and field notes. The various meanings behind participants' experiences were unpacked in relation to the literature and the broader socio-cultural contexts in which these experiences occurred. Findings highlighted issues with professional and informal interpreters. These issues included cost, discrepancies in dialect, translation outside appointments, and privacy. Findings indicate ethical and practical implications of using interpreters in healthcare for refugee women. A step to achieving equitable healthcare for refugee women in New Zealand entails putting in place accessible and robust communicative infrastructure.

Twelve-Week Mediterranean Diet Intervention Increases Citrus Bioflavonoid Levels and Reduces Inflammation in People with Type 2 Diabetes Mellitus.

The benefits of a Mediterranean Diet (MedDiet) in the management of diabetes have been reported, but the contribution of polyphenol-rich citrus fruit has not been studied widely. Here, we report the sub-study findings of a previously conducted MedDiet intervention clinical trial in patients with type 2 diabetes mellitus (T2DM), where we aimed to measure the diet intervention effects on plasma citrus bioflavonoids levels and biomarkers of inflammation and oxidative stress. We analysed plasma samples from 19 (of original 27) participants with T2DM who were randomly assigned to consume the MedDiet intervention or their usual diet for 12 weeks and then crossed over to the alternate diet. Compared with baseline, MedDiet significantly increased levels of the citrus bioflavonoids naringin, hesperitin and hesperidin (by 60%, 58% and 39%, respectively, p < 0.05) and reduced plasma levels of the pro-inflammatory cytokine IL-6 (by 49%, p = 0.016). Oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) decreased by 32.4% (p = 0.128). Usual diet did not induce these beneficial changes. The reduced inflammatory profile of T2DM participants may, in part, be attributed to the anti-inflammatory actions of citrus bioflavonoids. Together with indications of improved oxidative stress, these findings add to the scientific evidence base for beneficial consumption of citrus fruit in the MedDiet pattern.

The Nephroprotective Effect of Lycopene on Renal Ischemic Reperfusion Injury: A Mouse Model.

Acute kidney injury (AKI) is characterized by fast decline in renal function within a short period of time. Renal ischemic-reperfusion (I-R) injury is the main cause of AKI. This study aims to investigate the possible nephroprotective effect of lycopene on renal ischemic-reperfusion injury in mice model. Forty Swiss Albino adult male mice were randomly allocated onto one of the four study groups: sham group: mice had median laparotomy under anesthesia with no procedures performed, renal tissues and blood samples were collected. ischemic-reperfusion group (I-R-control): mice underwent median laparotomy under anesthesia, followed by 30 min bilateral renal ischemia. Renal tissues and blood samples were collected after 2 h from reperfusion. Vehicle-treated group: mice were pretreated with intra 1% dimethyl sulfoxide 30 min before inducing ischemia. Lycopene-treated group: mice were pretreated with 10 mg/kg intraperitoneal injection of lycopene 30 min before inducing renal ischemia. Renal tissues, and blood samples were collected after 2 h from reperfusion. Blood and tissue samples were collected to look for evidence of inflammation and necrosis. Blood urea nitrogen, serum creatinine as well as plasma NGAL levels were significantly increased in the active control group (P ≤ 0.05), when compared to the sham group. Similarly, renal levels of Notch2/Hes 1, TLR 2, IL-6, Bax, and F2-isoprostane were significantly increased in the active control group as compared to the sham group (P ≤ 0.05). Moreover, lycopene treatment was found to be significantly effective in reducing the increased levels of these markers after I-R injury (P ≤ 0.05).

Assessing urinary levels of IL-18, NGAL and albumin creatinine ratio in patients with diabetic nephropathy.

AIMS: Diabetic nephropathy (DN) is a serious microvascular complication of a longstanding hyperglycemia. This study aims to evaluate whether urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary Interleukin-18 possess a better diagnostic value than albumin creatinine ratio in assessing the severity of nephropathy in patients with type 2 diabetes mellitus (T2DM). MATERIAL & METHODS: Ninety participants diagnosed with T2DM were recruited and they were divided into three study groups according to their albumin/creatinine ratio (ACR): (Normoalbuminuria group, Microalbuminuria group, and Macroalbuminuria group). A matching of Ninety healthy subjects were included as controls. Blood and urine samples were collected to measure various markers of glycemic control and kidney function. RESULTS: IL-18 levels were not changed significantly between all study groups (P > 0.05), despite a significant positive correlation between IL-18 and urinary albumin levels. NGAL levels were significantly increased in Microalbuminuria group and Macroalbuminuria group as compared to the control and Normoalbuminuria groups. NGAL was also positively correlated with urinary albumin and ACR, but negatively correlated with the age and body mass index. Receiver Operating Characteristic curves revealed that for early detection of DN, the best cutoff values to discriminate DN and diabetic without nephropathy groups were ˃ 21.4 ng/ml for NGAL (94.67 sensitivity, 26.67% specificity), ≤0.34 pg/mL for IL-18 (72% sensitivity, 53.33% specificity), and ˃29.8 mg/g for ACR (80% sensitivity, 100% specificity). CONCLUSION: We conclude that the urinary ACR is a more accurate individual biomarker of DN when compared to both NGAL and IL-18.

Reno-protective effects of TAK-242 on acute kidney injury in a rat model.

Acute kidney inschemia/reperfusion (I/R) injury is characterized by an abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. Despite the advances in therapeutic techniques, the mortality and morbidity of patients remain high and have not appreciably improved. This study aims to evaluate the potential protective effect of TAK-242 on renal ischemia/reperfusion injury using an animal model. Thirty-five adult male Sprague-dawely rats (weighing 200-300), were assigned randomly into the following experimental groups (n = 7 in each group), Control (I/R), Sham (negative control), TAK-242 (5 mg/kg body weight), TAK-242 (10 mg/kg body weight) and Vehicle (DMSO). Rats were exposed to a 30 min of ischemia then 3 h of reperfusion. At the end of reperfusion phase, rats were sacrificed then plasma, serum and tissue samples were obtained to measure markers of kidney oxidative stress and inflammation. Plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), and tissue levels of interleukin-18 (IL-18) and malondialdehyde (MDA) were significantly lower in TAK-242 pretreated groups than the vehicle group and the control group (p < 0.05). Furthermore; serum levels of urea and creatinine were significantly lower in the TAK-242 pretreated groups as compared to the control group (p < 0.05). We conclude that administration of TAK-242 can be useful preventive method in attenuating the degree of acute kidney injury during ischemic reperfusion process as shown by a significant reduction of urinary inflammatory markers as well as significant reduction of urea and creatinine levels.

Trimetazidine attenuates the acute inflammatory response induced by Novolimus eluting bioresorbable coronary scaffold implantation.

BACKGROUND: This study aims to investigate the inflammatory response in Novolimus bioresorbable coronary scaffold implantation after a course treatment with trimetazidine (35mg tablet/twice daily for 4days). METHODS: This was a randomized single blind study. Forty diabetic patients with critical coronary stenosis were subjected to elective coronary scaffold implantation in Al-Najaf Center for Cardiac Surgery and Trans-Catheter Therapy, Najaf, Iraq, between January and July 2015. All patients were informed about the nature of the study and they signed the consent form before they included in the study. Patients were randomly allocated into the two study groups: Group 1 included 20 patients who did the elective coronary scaffold implementation without trimetazidine medication. Group 2 included 20 patients who did the elective coronary scaffold implementation with a course of the trimetazidine (35mg tablet/twice daily for 4days). RESULTS: There were significant reduction in the levels of the interleukin-6 and cardiac troponin-I in the trimetazidine-treated group (group 2) compared to the control group (group 1) (P<0.001), after 12h and 24h post-operative. This was associated with a significant rise in the levels of interleukin 10 in group 2 compared to group 1 (P<0.001). Pentraxin-3 was significantly reduced in group 2 but only 24h post-operative (P<0.006). CONCLUSION: Our study concluded that trimetazidine minimizes the acute inflammatory response occurred due to systemic release of inflammatory markers into blood in diabetic patients undergoing elective Novolimus bioresorbable coronary scaffold implementation.

A comparative study to illustrate the benefits of using ethinyl estradiol-cyproterone acetate over metformin in patients with polycystic ovarian syndrome.

AIM: This study was done to illustrate the clinical and biochemical effects of ethinyl estradiol-cyproterone acetate (EE-AC) and metformin in this disease. METHODS: This was a randomized control trial study, done on twenty-six female patients already diagnosed as cases of PCOS. Participants were divided into two study groups: group one (Group 1), received metformin of 500mg twice daily and the second group (Group 2), was given ethinyl estradiol-cyproterone acetate for 21 consecutive days followed by 7 days drug-free. The course of the treatment for both groups was continued for three consecutive months. RESULTS: Group 1 showed a statistical significant increase in serum high density lipoprotein cholesterol (HDL-C) levels (P=0.006) and a decrease in the level of triglyceride (TG) (P=0.006). In addition, Group 1 had a significant reduction in the levels of very density lipoprotein cholesterol (VLDL-C) (P=0.006). Group 2 had a significant increase in serum TG levels (P=0.01), associated with a significant decrease in serum LDL-C (P=0.04). Serum testosterone was significantly reduced in group 1 (P=0.038). This was associated with an improvement in glucose tolerance test (GTT) and BMI in the same group (group 1). Group 2, had an improvement in the menstrual cycle control; hirsutism and acne. CONCLUSION: This study showed that metformin treatment is beneficial in improving serum lipids; glucose homeostasis and BMI, however, the ethinyl estradiol-cyproterone acetate is superior in improving the clinical manifestation of patients with PCOS, including menstrual cycle regulation, hyperandrogenic state.

Simvastatin Use in Patients with Type 2 Diabetes Mellitus: The Effects on Oxidative Stress.

OBJECTIVES: Studies have shown that people with type 2 diabetes mellitus (T2DM) may develop atherosclerosis due to the disturbance in oxidative control and progressive dyslipidemia. Our study aimed to highlight the benefits of simvastatin treatment in improving serum lipids and reducing oxidative damage in patients with T2DM. METHODS: Our randomized control trial included 56 patients with T2DM and dyslipidemia. The participants were on glibenclamide (5mg/day) during the period of the study. The patients were divided into two study groups (groups 1 and 2). Group 1 was the control group and consisted of 31 patients. Group 2 consisted of 25 participants, who were given simvastatin 20mg tablet once daily for 12 weeks. The control group did not receive simvastatin. Both groups were followed-up for measurement of blood pressure, pulse rate, serum lipids, and parameters of oxidative stress. RESULTS: The simvastatin treated group showed a significant improvement with reduced erythrocyte glutathione compared to the control group (p<0.001). This was also associated with a significant reduction in erythrocyte malondialdehyde in the simvastatin treated group compared to the control group (p<0.001). Serum lipids reflected a similar improvement in the levels of erythrocyte malondialdehyde. CONCLUSION: Our study highlights the beneficial role of simvastatin in improving the degree of oxidative stress in patients with T2DM through its effects on serum lipids and lipid peroxidation.

Cardiovascular effects of copper deficiency on activity of superoxide dismutase in diabetic nephropathy.

BACKGROUND: Copper (Cu) is essential both for its role in antioxidant enzymes, like Cu/zinc (Zn) superoxide dismutase (SOD) and ceruloplasmin, as well as its role in lysyl oxidase, essential for the strength and integrity of the heart and blood vessels. With such a central role in cardiovascular health, Cu has been generally overlooked in the debate over improving our cardiovascular health. Cu deficiency has produced many of the same abnormalities present in cardiovascular disease. It seems almost certain that Cu plays a large role in the development of this killer disease, not because of its excess in the diet, but rather its deficiency. AIM: This study was undertaken to investigate the cardiovascular effects of Cu deficiency on the activity of SOD in patients with type 2 diabetes mellitus (T2DM) with and without diabetic nephropathy. MATERIALS AND METHODS: Fifty-five patients with T2DM were recruited in this study which were divided into two subgroups based on the presence of microalbuminuria, the first group (microal buminuric group, n = 31) had a microalbuminuria between 30 and 299 µg/mg. The second group (normoal buminuric group, n = 29) had an albumin level less than 30 µg/mg. The two diabetic groups were compared to the control group (n = 37). RESULTS: The results of our study showed a significant reduction in the levels of SOD enzyme associated with an increased urinary Cu excretion in microalbuminuric group compared to the control group at P < 0.05. CONCLUSIONS: The current study illustrates that the regulation of the blood concentrations of Cu may be a potential therapeutic target for prevention and treatment of diabetic nephropathy.