The main objective of this experiment was to determine the effects of yogurt supplementation on fat deposition, oxidative stress, inflammation and fibrosis in the liver of rats with high-fat (HF) diet-induced obesity. Male Wistar rats were used in this study and were separated into the following four different groups: the control, control + yogurt, high fat and high fat+ yogurt groups. The high fat groups received a HF diet for eight weeks. A 5% yogurt (w/w) supplement was also provided to rats fed the HF diet. Yogurt supplementation prevented glucose intolerance and normalized liver-specific enzyme activities in the HF diet-fed rats. Yogurt supplementation also significantly reduced the levels of oxidative stress markers in the plasma and liver of HF diet-fed rats. Moreover, inflammatory cell infiltration, collagen deposition and fibrosis in the liver of HF diet-fed rats were also prevented by yogurt supplementation. Furthermore, yogurt supplementation normalized the intestinal lining and brush border in HF diet-fed rats. This study suggests that yogurt supplementation potentially represents an alternative therapy for the prevention of metabolic syndrome in HF diet-fed rats.

Diabetes is a leading cause of chronic kidney disease, and the high prevalence of sympathetic nervous system (SNS) hyperactivity in diabetic patients makes them further susceptible to SNS-mediated oxidative stress and accelerated kidney damage. Here, we investigated if canagliflozin can reverse isoprenaline (ISO)-induced renal oxidative damage in rats, a model that mimics SNS overstimulationinduced organ injuries in humans. We found that ISO administration elevates renal oxidative stress markers including malondialdehyde (MDA), advanced protein oxidation product (APOP), myeloperoxidase (MPO) and nitric oxide (NO), while depleting levels of endogenous antioxidants such as catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH). Strikingly, canagliflozin treatment of ISO-treated rats not only prevents elevation of oxidative stress markers but also rescues levels of depleted antioxidants. Our results also show that canagliflozin stimulates antioxidant/antiinflammatory signaling pathways involving AMP-activated protein kinase (AMPK), Akt and eNOS, and inhibits iNOS and NADPH oxidase isoform 4 (NOX4), all of which are associated with oxidative stress and inflammation. Further, canagliflozin prevents ISO-induced apoptosis of kidney cells by inhibiting Bax protein upregulation and caspase-3 activation. Histological examination of kidney sections reveal that canagliflozin attenuates ISO-mediated increases in inflammatory cell infiltration, collagen deposition and fibrosis. Finally, consistent with these findings, canagliflozin treatment improves kidney function in ISO-treated rats, suggesting that the antioxidant effects may be clinically translatable. Diabetic kidney disease is a major risk factor for the development of chronic kidney disease affecting approximately 40% of global diabetic population 1. Diabetic kidney disease is associated with vascular inflammation, loss of renal vascular integrity and hypertension, leading to a progressive loss of renovascular function and renal failure 1. Importantly, there is a high prevalence of sympathetic nervous system (SNS) hyperactivity in diabetic patients associated with autonomic neuropathy and concomitant vagal impairment, making diabetic patients twice as likely to develop hypertension 2. Diabetic patients are also highly susceptible to chronic kidney disease due to renal oxidative damage and inflammation 2. High SNS drive stimulates β1 adrenergic receptors (β1-AR) in juxtaglomerular cells, increasing renin secretion and subsequent activation of the renin-angiotensin-aldosterone system (RAAS). RAAS creates a feed-forward mechanism that accelerates renovascular dysfunction and kidney

The antidiabetic drug canagliflozin is reported to possess several cardioprotective effects. However, no studies have investigated protective effects of canagliflozin in isoprenaline (ISO)-induced cardiac oxidative damage-a model mimicking sympathetic nervous system (SNS) overstimulation-evoked cardiac injuries in humans. Therefore, we investigated protective effects of canagliflozin in ISOinduced cardiac oxidative stress, and their underlying molecular mechanisms in Long-Evans rat heart and in HL-1 cardiomyocyte cell line. Our data showed that ISO administration inflicts pro-oxidative changes in heart by stimulating production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). In contrast, canagliflozin treatment in ISO rats not only preserves endogenous antioxidants but also reduces cardiac oxidative stress markers, fibrosis and apoptosis. Our Western blotting and messenger RNA expression data demonstrated that canagliflozin augments antioxidant and anti-inflammatory signaling involving AMP-activated protein kinase (AMPK), Akt, endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In addition, canagliflozin treatment attenuates pro-oxidative, pro-inflammatory and proapoptotic signaling mediated by inducible nitric oxide synthase (iNOS), transforming growth factor beta (TGF-β), NADPH oxidase isoform 4 (Nox4), caspase-3 and Bax. Consistently, canagliflozin treatment improves heart function marker in ISO-treated rats. In summary, we demonstrated that canagliflozin produces cardioprotective actions by promoting multiple antioxidant and antiinflammatory signaling. Canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, belongs to a new class of antidiabetic drugs prescribed for the management of type 2 diabetes mellitus (T2DM) 1. Accumulating evidence suggests that canagliflozin exhibits a range of cardiovascular effects that are independent of glucose lowering. According to recent preclinical and clinical data, canagliflozin treatment significantly reduced risk of cardiovascular death, myocardial infarction (MI), stroke and hospitalization due to heart failure in both diabetic and non-diabetic subjects 2-5. Proposed mechanisms for cardiovascular benefits of canagliflozin include improvement of cardiac metabolism and diastolic function, reduction of vascular stiffness, and an overall reduction of blood pressure 5-9. A growing body of evidence suggests that canagliflozin possess antioxidant and anti-inflammatory actions in various cellbased and animal models 10-14. Canagliflozin was shown to reduce vascular inflammation and atherosclerosis by

No abstract

No abstract

Plant-derived natural products have shown beneficial effects in many diseases associated with liver. The present study aimed to appraise the effects of Trichosanthes dioica (TD) peel extract on oxidative stress, inflammation as well as fibrosis exhibited by the ovariectomized rats in which hepatic damage had been induced by the administration of carbon tetrachloride (CCl 4). The CCl 4 administration in the ovariectomized rats elevated the plasma ALT, AST, and ALP level in comparison with the control while TD peel extract showed significant reduction of those activities. Besides, oxidative stress and lipid peroxidation also increased in CCl 4treated rats. TD peel extract significantly reduced the oxidative stress marker's concentration and improved the catalase and SOD activities in CCl 4-administered ovariectomized rats. These results suggest that TD peel extract is capable of protecting the liver from CCl 4 induced damage through preventing oxidative stress, lipid

No abstract

The antidiabetic drug canagliflozin, a SGLT2 inhibitor, has been reported to possess protective effects against ischemia‐reperfusion and chemically‐induced cardiac and renal injuries. However, to our knowledge, no studies have investigated the protective effects of canagliflozin in isoprenaline (ISO)‐induced cardiac and renal oxidative damage – a model mimicking sympathetic nervous system (SNS) overstimulation‐evoked organ injuries in humans. Therefore, we investigated effects of canagliflozin in ISO‐induced cardiac and renal oxidative stress, and their underlying molecular mechanisms. Our tissue biochemistry, histology, and Western blotting data showed that ISO administration inflicted pro‐oxidative, pro‐inflammatory and pro‐apoptotic changes in the heart and kidney tissues. In contrast, treatment with canagliflozin at 5 mg/kg body weight attenuated levels of cardiac and renal oxidative stress markers including malondialdehyde (MDA), advanced protein oxidation product (APOP), myeloperoxidase (MPO) and nitric oxide (NO), and restored levels of endogenous antioxidant molecules such as catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) that were depleted in ISO‐treated rats. Western blot analysis revealed that canagliflozin increased activity of anti‐oxidant/anti‐inflammatory proteins such as AMP‐activated protein kinase (AMPK), Akt and eNOS, and decreased pro‐oxidative/pro‐inflammatory proteins including iNOS and NADPH oxidase isoform 4 (NOX4). Protein expression analysis further revealed that ISO increased the ratio of pro‐apoptotic/anti‐apoptotic protein (Bax:Bcl‐2) expression, which was significantly reduced by canagliflozin treatment. Our histological examination demonstrated that in the heart and kidney tissue sections, canagliflozin attenuated ISO‐induced histopathological changes, including inflammatory cell infiltration, collagen deposition, and fibrosis. Consistent with our biochemical data, canagliflozin augmented heart and kidney functions in ISO rats, further supporting a protective role of this drug in ISO‐induced oxidative stress. In summary, we show that canagliflozin produces cardioprotective and renoprotective actions via suppression of iNOS, NOX4 and Bax, and activation of AMPK‐Akt‐eNOS‐NO signaling axis. Support or Funding Information This work was supported by a start‐up grant from the Mercer University College of Pharmacy to Dr. Raquibul Hasan and a research grant from North South University to Dr. Md Ashraful Alam