Resveratrol treatment modulates several antioxidant and anti-inflammatory genes expression and ameliorated oxidative stress mediated fibrosis in the kidneys of high-fat diet-fed rats.

Objective: Resveratrol is a polyphenolic compound that possesses strong antioxidant and anti-inflammatory activities. This study evaluated the effects of resveratrol on oxidative stress, fibrosis and multiple genes regulation in the kidneys of high fat (HF) diet-fed rats. Methods: Wistar rats were fed with HF diet for eight weeks. These rats were also treated with resveratrol for eight weeks. Finally, kidney tissue samples were isolated from all sacrificed rats. The histological changes, creatinine and uric acid levels, oxidative stress parameters such as malondialdehyde (MDA), nitric oxide, and advanced oxidation protein product (AOPP) levels were analyzed. The antioxidant enzymes such as catalase, superoxide dismutase (SOD) activities and reduced glutathione (GSH) levels; gene expression of inflammatory and fibrosis-related genes namely, inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta1 (TGF-ß1), and collagen-1 were assessed. Moreover, gene expression of oxidative stress-related genes such as nuclear factor erythroid 2-related factor 2 (Nrf-2), SOD, catalase, and glutathione reductase, were also assessed. Results: HF diet-fed rats showed increased creatinine and uric acid levels in plasma which were lowered by resveratrol treatment. The study findings also revealed that resveratrol counterbalanced the oxidative stress and prevented the expression of the inflammatory genes; restored the catalase and SOD activities followed by the up-regulation of antioxidant genes expression in the kidneys of HF diet-fed rats. HF diet caused the Nrf-2 down-regulation followed by the decreased expression of HO-1 and HO-2 genes, which was restored by resveratrol treatment. Moreover, the histological assessment showed lipotoxicity and increased fibrosis in the kidneys of HF diet-fed rats. Resveratrol prevented the kidney fibrosis probably by limiting oxidative stress, inflammation, and down-regulating TGF-ß1 mediated signaling pathway. Conclusion: In conclusion, resveratrol treatment showed beneficial effects in preventing oxidative stress and fibrosis in the kidneys of HF diet-fed rats probably by modulating the gene expression of oxidative stress and inflammation related factors and enzymes.

Protective effects of l-carnitine on isoprenaline -induced heart and kidney dysfunctions: Modulation of inflammation and oxidative stress-related gene expression in rats.

The aim of this study was to evaluate the effect of l-carnitine (L-CAR) treatment on isoprenaline (ISO) administered kidney and heart impairment in male Long Evans rats. Four groups of rats were engaged in this study such as control, ISO, control + L-CAR, and ISO + L-CAR, where n = 6 in each group. The rats were also provided with chow food and water ad libitum. At the end of the study, all rats were sacrificed, and blood and tissue samples were collected for bio-chemical analysis. Oxidative stress parameters and antioxidant enzyme activities were determined in plasma and tissues. Antioxidant and inflammatory genes expression were analyzed in the kidney cortex, and histopathological studies of kidney tissues were performed. This study showed that creatinine and uric acid in plasma were significantly increased in ISO-administered rats. l-carnitine treatment lowered the uric acid and creatinine level. ISO-administered rats showed increased lipid peroxidation and declined levels of antioxidant enzymes activities in kidneys and heart. l-carnitine treatment restored antioxidant enzymes activities and protect against oxidative stress in kidney and heart. This effect is correlated with the restoration of Nrf-2-HO-1 genes expression followed by increased SOD and catalase genes expression in the kidney. l-carnitine treatment also prevented the TNF-α, IL-6, and NF-кB expression in kidneys of ISO administered rats. Histopathology staining showed that l-carnitine treatment prevented kidney damage and collagen deposition in ISO administered rats. The result of this study exhibited that l-carnitine treatment reduced oxidative stress and increased antioxidant enzyme activities by enhancing antioxidant genes expression in ISO administered rats.

Crataeva nurvala Bark (Capparidaceae) Extract Modulates Oxidative Stress-Related Gene Expression, Restores Antioxidant Enzymes, and Prevents Oxidative Stress in the Kidney and Heart of 2K1C Rats.

Objective: Crataeva nurvala is a medicinal plant, which contains a wide range of polyphenolic and bioactive compounds. The aim of the study was to evaluate the renal-protective activity of Crataeva nurvala in two-kidney, one-clip (2K1C) rats. Methods: In this study, the ethanol extract of Crataeva nurvala bark at a dose of 100 mg/kg was orally used to treat 2K1C rats for four weeks. At the end of the experiment, all rats were sacrificed and tissue samples were collected for further biochemical and histological assessments. Results: This investigation showed that Crataeva nurvala treatment prevented the kidney dysfunction in 2K1C rats. Uric acid and creatinine concentration and CK-MB activities increased in 2K1C rats which were normalized by Crataeva nurvala. 2K1C rats also showed increased oxidative stress, depicted by the elevated level of MDA, NO, and APOP in plasma and tissues. Oxidative stress parameters declined in 2K1C rats by the treatment of Crataeva nurvala. These results could be attributed to the restoration of antioxidant enzyme activities such as catalase and SOD. Crataeva nurvala extracts also upregulated antioxidant gene expression in the kidneys of 2K1C rats. Moreover, several anti-inflammatory genes were suppressed by Crataeva nurvala treatment in 2K1C rats. Furthermore, fibrosis and collagen deposition in the kidneys were also lowered by the treatment of the Crataeva nurvala extract. Conclusion: The experimental data suggest that the Crataeva nurvala extract protected renal damage and oxidative stress, probably by restoring antioxidant enzymes activities in 2K1C rats.

Flacourtia indica fruit extract modulated antioxidant gene expression, prevented oxidative stress and ameliorated kidney dysfunction in isoprenaline administered rats.

This study evaluated the effect of Flacourtia indica fruit extract against isoprenaline (ISO) induced renal damage in rats. This investigation showed that ISO administration in rats increased the level oxidative stress biomarkers such as malondialdehyde (MDA), nitric oxide (NO), advanced protein oxidation product (APOP) in kidneys followed by a decrease in antioxidant enzymes functions. Flacourtia indica fruit extract, which is rich in strong antioxidants, also reduced the MDA, NO and APOP level in kidney of ISO administered rats. Inflammation and necrosis was also visible in kidney section of ISO administered rats which was significantly prevented by atenolol and Flacourtia indica fruit extract. Moreover, atenolol and Flacourtia indica fruit extract also modulated the genes expressions related to inflammation and oxidative stress in kidneys. The beneficial effects could be attributed to the presence of a number of phenolic antioxidants. This study suggests that Flacourtia indica fruit extract may prevent kidney dysfunction in ISO administered rats, probably by preventing oxidative stress and inflammation.

Leaf powder supplementation of Senna alexandrina ameliorates oxidative stress, inflammation, and hepatic steatosis in high-fat diet-fed obese rats.

Obesity is an enduring medical issue that has raised concerns around the world. Natural plant extracts have shown therapeutic potential in preventing oxidative stress and inflammation related to obesity complications. In this study, Senna alexandrina Mill. leaves were utilized to treat high-fat diet-related metabolic disorders and non-alcoholic fatty liver diseases. Plasma biochemical assays were conducted to determine the lipid profiles and oxidative stress parameters, and the gene expression of antioxidant enzymes and inflammatory mediators was measured. Histological stained livers of high-fat diet-fed rats were observed. S. alexandrina leaf powder supplementation prevented the increase in cholesterol and triglyceride levels in high-fat diet-fed rats. Moreover, S. alexandrina leaves also reduced lipid peroxidation and nitric oxide production in these rats. Prevention of oxidative stress by S. alexandrina leaf supplementation in high-fat diet-fed rats is regulated by enhancing the antioxidant enzyme activity, followed by the restoration of corresponding gene expressions, such as NRF-2, HO-1, SOD, and CAT. Histological staining provides further evidence that S. alexandrina leaf supplementation prevents inflammatory cell infiltration, lipid droplet deposition, and fibrosis in the liver of high-fat diet-fed rats. Furthermore, this investigation revealed that S. alexandrina leaf supplementation controlled non-alcoholic fatty liver disease by modulating the expression of fat metabolizing enzymes in high-fat diet-fed rats. Therefore, S. alexandrina leaf supplementation inhibits fatty liver inflammation and fibrosis, suggesting its usefulness in treating non-alcoholic steatohepatitis. Thus, this natural leaf extract has potential in treatment of obesity related liver dysfunction.

Canagliflozin attenuates isoprenaline-induced cardiac oxidative stress by stimulating multiple antioxidant and anti-inflammatory signaling pathways.

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 ISO-induced 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 pro-apoptotic signaling mediated by inducible nitric oxide synthase (iNOS), transforming growth factor beta (TGF-ß), 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 anti-inflammatory signaling.