Efficacy of Caffeic Acid on Diabetes and Its Complications in the Mouse.

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg kg-1). Two days later, CA (50 mg kg-1) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice.

Chemotherapeutic potential of quercetin on human bladder cancer cells.

In an effort to improve local bladder cancer control, we investigated the cytotoxic and genotoxic effects of quercetin on human bladder cancer T24 cells. The cytotoxic effect of quercetin against T24 cells was examined by MTT test, clonogenic assay as well as DNA damaging effect by comet assay. In addition, the cytotoxic effect of quercetin on the primary culture of papillary urothelial carcinoma (PUC), histopathological stage T1 of low- or high-grade tumours, was investigated. Our analysis demonstrated a high correlation between reduced number of colony and cell viability and an increase in DNA damage of T24 cells incubated with quercetin at doses of 1 and 50 µM during short term incubation (2 h). At all exposure times (24, 48 and 72 h), the efficacy of quercetin, administered at a 10× higher dose compared to T24 cells, was statistically significant (P < 0.05) for the primary culture of PUC. In conclusion, our study suggests that quercetin could inhibit cell proliferation and colony formation of human bladder cancer cells by inducing DNA damage and that quercetin may be an effective chemopreventive and chemotherapeutic agent for papillary urothelial bladder cancer after transurethral resection.

Assessment of DNA damage and lipid peroxidation in diabetic mice: effects of propolis and epigallocatechin gallate (EGCG).

There is growing recognition that polyphenolic compounds present in many plants and natural products may have beneficial effects on human health. Propolis - a substance produced by honeybees - and catechins in tea, in particular (-)-epigallocatechin gallate (EGCG), are strong antioxidants that appear to have anti-obesity and anti-diabetic effects. The present study was designed to elucidate the anti-diabetic effect of the water-soluble derivative of propolis (WSDP), which contains phenolic acids as the main compounds, and EGCG in alloxan-induced (75mg/kg, iv) diabetes in mice. Intraperitoneal administration of EGCG or propolis at doses of 50mg/kg body weight (bw) to diabetic mice for a period of 7 days resulted in a significant increase in body weight and in haematological/immunological blood parameters, as well as in 100% survival of the mice. A significant decrease in lipid peroxidation in liver, kidney and brain tissue was also observed in diabetic mice treated with these two agents. Additionally, EGCG and propolis clearly reduced DNA damage in peripheral lymphocytes of diabetic mice. Our studies demonstrate the anti-oxidative and anti-inflammatory potential of WSDP and EGCG, which could exert beneficial effects against diabetes and the associated consequences of free-radical formation in kidney, liver, spleen and brain tissue. The results suggest that dietary supplementation with WSDP or EGCG could potentially contribute to nutritional strategies for the prevention and treatment of diabetes mellitus.

Effect of Croatian propolis on diabetic nephropathy and liver toxicity in mice.

BACKGROUND: In the present study, we examined the antioxidant effect of water soluble derivative of propolis (WSDP) and ethanolic (EEP) extract of propolis on renal and liver function in alloxan-induced diabetic mice. In addition, we examined whether different extract of propolis could prevent diabetic nephropathy and liver toxicity by inhibiting lipid peroxidation in vivo. METHODS: Diabetes was induced in Swiss albino mice with a single intravenous injection of alloxan (75 mg kg-1). Two days after alloxan injection, propolis preparations (50 mg kg-1 per day) were given intraperitoneally for 7 days in diabetic mice. Survival analysis and body weights as well as hematological and biochemical parameters were measured. The renal and liver oxidative stress marker malonaldehyde levels and histopathological changes were monitored in the liver and kidney of treated and control mice. RESULTS: Administration of propolis to diabetic mice resulted in a significant increase of body weight, haematological and immunological parameters of blood as well as 100% survival of diabetic mice. Alloxan-injected mice showed a marked increase in oxidative stress in liver and kidney homogenate, as determined by lipid peroxidation. Histopathological observation of the liver sections of alloxan-induced diabetic mice showed several lesions including cellular vacuolization, cytoplasmic eosinophilia and lymphocyte infiltrations, but with individual variability.Treatment of diabetic mice with propolis extracts results in decreased number of vacuolized cells and degree of vacuolization; propolis treatment improve the impairment of fatty acid metabolism in diabetes. Renal histology showed corpuscular, tubular and interstitial changes in alloxan-induced diabetic mice. Test components did not improve renal histopathology in diabetic mice. CONCLUSIONS: Propolis preparations are able to attenuate diabetic hepatorenal damage, probably through its anti-oxidative action and its detoxification proccess as well as the potential to minimize the deleterious effects of free radicals on tissue. The protective role of propolis against the ROS induced damages in diabetic mice gives a hope that they may have similar protective action in humans.

Naringenin ameliorates pathological changes in liver and kidney of diabetic mice: a preliminary study.

The effect of naringenin, a flavonoid found in grapefruit, orange, and tomato, on lipid peroxidation and histopathological changes in the liver and kidneys of alloxan-induced diabetic mice were investigated. Two days after alloxan injection (75 mg kg-1, i.v.), naringenin ethanolic solution (0.5 % v/v) was given to mice intraperitoneally (50 mg kg-1 per day) for seven days. Naringenin's impact on lipid peroxidation was measured by the 2-thiobarbituric acid test and histopathological changes were examined under a light microscope. Naringenin administration resulted in a significant decrease of lipid peroxidation level in liver and kidney tissue, as well as in a decreased number of vacuolated liver cells and degree of vacuolisation. Indications of tissue repair in kidney suggested that amelioration of diabetes-induced renal damage could be achieved over a longer period of time. Findings suggest that naringenin could be considered a dietary supplement in the prevention or treatment of diabetic complications and other diseases connected with oxidative stress, and gives a hope that it could show similar effects in the treatment of diabetes in humans.

DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice.

Diabetes mellitus is associated with a high production of reactive oxygen species, which may cause oxidative DNA damage. High levels of genomic damage have been associated with liver and renal failure as well as immune-system decline. Flavonoids are effective antioxidants and may protect against several chronic diseases including diabetes. This study used the comet assay to assess the levels of DNA damage in the blood, liver and kidney cells in untreated and quercetin (QU) or naringenin treated diabetic mice. In addition, the study was designed to establish whether QU or naringenin might have a biological effect in protecting diabetic mice against oxidative stress by using survival studies to observe total body injury at the level of the organism. QU or naringenin were injected to mice intraperitoneally (i.p.) at a dose of 50mg/kg for 7days starting 2days after a single dose (75mg/kg, i.v.) alloxan injection. These findings suggest that QU or naringenin treatment resulted in a significant increase in the body weight, the haematological and immunological parameters of blood, as well as leading to 100% survival of diabetic mice. The tested flavonoids have protective effects against alloxan-induced DNA-damage in peripheral lymphocytes but not in the liver and kidney cells of diabetic mice. It might be hypothesised that diabetic mice with a high intake of flavonoid-rich foods, and specifically foods rich in quercetin or naringenin, might be relatively protected against long-term complications of diabetes due to decreased oxidative stress. Various co-operative and synergistic action mechanisms of the tested flavonoids may lead to the protection of the whole organism against diabetes.