A focus on resveratrol and ocular problems, especially cataract: From chemistry to medical uses and clinical relevance.

Low vision and blindness are important health problems that affect millions of people throughout the world. The most common and important pathologies are diabetic retinopathy, age-related macular degeneration, glaucoma as well as cataracts. The latter consists of an opacification of the lens of the eye which impedes the passage of light and represents one of the most important causes of vision loss. Among the risk factors for cataract development, there are life-style factors such as the use of tobacco, abuse of alcohol and unhealthy diet. In light of this, dietary components that possess anti-oxidant activity, such as polyphenols for instance, can be considered good candidates for human studies in the prevention and or treatment of such diseases. Among dietary components, the antioxidant capacity of certain polyphenols is well known, and these could be good candidates. In this review we focus our attention on the current scientific literature regarding to the effects of resveratrol on cataracts and other ocular diseases, along with its potential mechanism/s of action. A large number of preclinical studies support the involvement of resveratrol in clinical trials for the prevention and treatment of eye diseases induced by oxidative stress and inflammation, such as age-related cataract.

Zeaxanthin and ocular health, from bench to bedside.

Cataracts, glaucoma, and age-related macular degeneration are known as major ocular problems which cause blindness among the elderly population worldwide. Oxidative stress plays an important role in both the initiation and progression of ocular problems and with respect to this; dietary antioxidants can serve as a therapeutic strategy for the improvement of ocular health. Zeaxanthin is known as one of the most important and common xanthophyll carotenoids, possessing multiple therapeutic effects such as strong antioxidant and pro-oxidant behaviour as well as anti-inflammatory effects. A growing body of literature shows that zeaxanthin mitigates ocular problems and suppresses oxidative stress in the retinal tissues. This paper aims to critically review the available literature regarding the beneficial effects of zeaxanthin on ocular problems with emphasis on its chemistry, bioavailability, and sources.

Curcumin: a natural product for diabetes and its complications.

Curcumin is the yellow-colored bioactive constituent of the perennial plant, Curcuma longa L., which possesses a wide range of physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective and anti-diabetic activities. Anti-diabetic activity of curcumin may be due to its potent ability to suppress oxidative stress and inflammation. Moreover, it shows a beneficial role on the diabetesinduced endothelial dysfunction and induces a down-regulation of nuclear factor-kappa B. Curcumin possesses a protective role against advanced glycation as well as collagen crosslinking and through this way, mitigates advanced glycation end products-induced complications of diabetes. Curcumin also reduces blood glucose, and the levels of glycosylated hemoglobin in diabetic rat through the regulation of polyol pathway. It also suppresses increased bone resorption through the inhibition of osteoclastogenesis and expression of the AP-1 transcription factors, c-fos and c-jun, in diabetic animals. Overall, scientific literature shows that curcumin possesses anti-diabetic effects and mitigates diabetes complications. Here we report a systematical discussion on the beneficial role of curcumin on diabetes and its complications with emphasis on its molecular mechanisms of actions.

Ameliorative effect of ferulic acid against renal injuries mediated by nuclear factor-kappaB during glycerol-induced nephrotoxicity in Wistar rats.

The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves ischemia, vascular congestion and reactive oxygen metabolites. In this study, we have investigated for the first time, the role of ferulic acid in attenuating glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8 mL/kg body weight of 50% glycerol, glycerol + ferulic acid at the dose of 5, 10, 15, 20 and 25 mg/kg body weight. After 24 h, the rats were sacrificed and the kidneys were removed for histological and immunohistochemical studies. Furthermore, determinations of lipid peroxidation (LPO) as well as antioxidant enzymes were also analyzed; blood, urine samples were collected in order to quantify renal function and nitric oxide generation, respectively. Glycerol-induced rats showed a significant increase in the level of urinary markers assessed in serum as well as kidney and these were reversed upon ferulic acid treatment. A significant increase in urine nitric oxide, serum as well as kidney LPO, decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in glycerol-induced rats. Immunohistochemical study in glycerol-induced rats demonstrated an increase in the level of nuclear factor-kappaB (NF-κB). All these effects induced by glycerol were reduced upon treatment with ferulic acid in a dose-dependent manner. To conclude, ferulic acid enhances antioxidants and decreases NF-κB, thereby protecting the cells against stress induced by glycerol.

Ameliorative effects of curcumin against renal injuries mediated by inducible nitric oxide synthase and nuclear factor kappa B during gentamicin-induced toxicity in Wistar rats.

The ameliorative role of curcumin in attenuating gentamicin-induced nephrotoxicity has been reported earlier however, the mechanism of action remains unclear. Gentamicin was injected intraperitoneally (100 mg/kg body weight) once daily for 6 days. Curcumin was administered orally (200 mg/kg body weight) once daily for 7, 15 and 30 days. Gentamicin-induced rats showed significant increase in the levels of kidney markers and the activities of urinary marker enzymes, which was reversed upon curcumin treatment. A significant increase in kidney lipid peroxidation (LPO) and decrease in activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) were observed in gentamicin-induced rats. Immunohistochemical, Western blot and RT-PCR studies in gentamicin-induced rats also demonstrated an increase in the levels of inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB). All these effects induced by gentamicin were reduced upon treatment with curcumin in a time dependent manner. To conclude, curcumin enhances antioxidants, and decreases iNOS and NF-κB, thereby protecting the cells against oxidative stress induced by gentamicin.

1, 2 di-substituted idopyranose from Vitex negundo L. protects against streptozotocin-induced diabetes by inhibiting nuclear factor-kappa B and inducible nitric oxide synthase expression.

The aim of this study is to investigate the mechanism of an action of compound isolated from Vitex negundo in streptozotocin-induced diabetic mice. Light microscopic examination of liver, kidney and pancreatic sections of streptozotocin-induced diabetic mice showed changes like coarsening of acinar cells of endoplasmic reticulum, destruction of ß-cells, and alteration in their secretory function were observed in the pancreas. Changes like dilation of vein, unusual concentric arrangement of hepatocytes, and liver fibrosis were observed in the liver. Thickening of tubules and expansion of glomerulus were observed in kidneys. All these altered parameters were reversed close to normal condition upon treatment using idopyranose. The results show the antidiabetic potential of idopyranose. Interestingly, liver, kidney, and pancreatic sections of diabetic mice fed with the isolated 1, 2 di-substituted idopyranose showed regeneration of hepatocytes, nephrocytes, as well as ß-cells and acinar region appeared normal with increased numbers of ß-cells. To understand the probable mechanism of action of 1, 2 di-substituted idopyranose, we analyzed proinflammatory inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) expression by immunohistochemistry and the results showed an increased iNOS and NF-κB levels in streptozotocin-induced diabetic liver, kidney and pancreas. Such high iNOS and NF-κB levels were inhibited in 1, 2 di-substituted idopyranose treated mice. The results suggest that 1, 2 di-substituted idopyranose helps in the protection of hepatocytes, nephrocytes and pancreatic ß-cells probably by its action against NF-κB and iNOS mediated inflammation in streptozotocin-induced diabetes.

Curcumin prevents free radical-mediated cataractogenesis through modulations in lens calcium.

The generation of free radicals has been implicated in the causation of cataract, and compounds that can scavenge free radicals ameliorate the disease process. This study investigated the possible free radical scavenging potential of curcumin at a dose of 75 mg/kg body wt on selenium-induced cataract in rat pups. Intraperitoneal injection of sodium selenite (15 micromol/kg body wt) into 8- to 10-day-old rat pups led to severe oxidative stress in the eye lens as evidenced by increased nitric oxide, superoxide anion, and hydroxyl radical generation and inducible nitric oxide synthase expression that probably led to cataract formation. Selenium exposure also caused an increase in total calcium in the eye lens and significantly inhibited the activity of Ca(2+) ATPase but not Na(+)/K(+) ATPase or Mg(2+) ATPase. On the other hand, pretreatment with curcumin, but not simultaneous or posttreatment, led to a decrease in oxidative stress and also rescued the selenium-mediated increase in lens Ca(2+) and inhibition of Ca(2+) ATPase activity in the eye lens. The results of this study demonstrate that an increase in free radical generation triggered by selenium could cause inactivation of lens Ca(2+) ATPase leading to Ca(2+) accumulation. This enhanced Ca(2+) can cause activation of calpain-mediated proteolysis in the lens, resulting in lens opacification. Curcumin in this study was able to prevent selenium-induced oxidative stress leading to activation of Ca(2+) ATPase and inhibition of lens opacification. Thus, curcumin has the potential to function as an anticataractogenic agent, possibly by preventing free radical-mediated accumulation of Ca(2+) in the eye lens.

Curcumin protects against hepatic and renal injuries mediated by inducible nitric oxide synthase during selenium-induced toxicity in Wistar rats.

The aim of this study is to evaluate the effect of curcumin in protecting against selenium-induced toxicity in liver and kidney of Wistar rats. Light microscopy evaluation of selenium alone administered rats showed liver to be infiltrated with mononuclear cells, vacuolation, necrosis, and pronounced degeneration. Control liver sections showed a regular morphology of parenchymal cells with intact hepatocytes and sinusoids. Kidney from selenium alone administered rats showed vacuolar degeneration changes in the epithelial cells, cellular proliferation with fibrosis, thickening of capillary walls, and glomerular tuft atrophy. Such changes were also observed in rats administered with selenium and curcumin simultaneously and rats administered first with selenium and then curcumin 24 h later. Interestingly, such degenerative changes observed in liver and kidney induced by selenium were not seen in rats that were administered with curcumin first and selenium 24 h later. This clearly suggests the protective nature of curcumin against selenium toxicity. To understand the probable mechanism of action of curcumin, we analyzed inducible nitric oxide synthase (iNOS) expression by immunohistochemistry, and the results showed an increased iNOS expression in selenium-alone induced liver and kidney. Such high iNOS levels were inhibited in liver and kidney of rats pretreated with curcumin and then with selenium 24 h later. Based on the histological results, it can be concluded that curcumin functions as a protective agent against selenium-induced toxicity in liver as well as kidney, and this action is probably by the regulatory role of curcumin on iNOS expression.

Effect of black tea on histological and immunohistochemical changes in pancreatic tissues of normal and streptozotocin-induced diabetic mice (Mus musculus).

The aim of the present study is to evaluate the effect of hot water extract of black tea in regenerating beta cells in streptozotocin-induced diabetic mice. Light microscopic examination of pancreatic sections of streptozotocin-induced diabetic mice showed the acinar cells to be small, shrunken, and with deteriorated beta cells. The dose of streptozotocin not only altered the function of beta cells but also damaged the acinar region. The changes in acinar cells were coarsening of endoplasmic reticulation suggesting alteration in their secretory function. The control pancreatic tissue showed well-defined granulated islets and dark beta cells when stained with chrome hematoxylin and phloxine. Interestingly, pancreatic sections of diabetic mice fed with black-tea extract showed regeneration of beta cells and acinar region appeared normal with increased numbers of beta cells. To understand the probable mechanism of action of black-tea extract, we analyzed inducible nitric oxide synthase (iNOS) expression by immunohistochemistry and the results showed an increased iNOS levels in streptozotocin-induced diabetic pancreas, and such high iNOS levels were inhibited in black-tea extract treated mice. According to histological results obtained, it can be concluded that the black-tea extract helps in regeneration of damaged pancreas and protects pancreatic beta cells by its antioxidant action against nitrosative stress in streptozotocin-induced diabetes.

In vitro generation of superoxide anion by the hemocytes of Macrobrachium rosenbergii: possible mechanism and pathways.

The hemocytes from the giant freshwater prawn Macrobrachium rosenbergii were examined for their ability to generate superoxide anion (O(2) (-)) in vitro upon exposure to various components derived from microbial cell wall components. Among the test molecules, laminarin (a polymer of beta-1, 3 glucans), mannan and LPS from five different bacterial species produced a differential response in terms of stimulated O(2) (-) production in prawn hemocytes, suggesting the ability of the hemocytes to differentiate non-self. This response was almost completely inhibited by superoxide dismutase (SOD) suggesting SOD-inhibitable O(2) (-) generation by prawn hemocytes. Phorbol 12-myristate 13-acetate (PMA) and Ca ionophore led to enhanced O(2) (-) generation by the hemocytes and this suggests the possible role of protein kinase C and Ca(2+) ions in such generation. Cytochemical analysis using nitroblue tetrazolium (NBT)-staining revealed the importance of granular hemocytes in O(2) (-) generation in these prawns. Inhibition of O(2) (-) generation by inhibitors of NADPH-oxidase and phenoloxidase pathways clearly reveal the involvement of two different pathways in non-self stimulated O(2) (-) generation by the prawn hemocytes. These findings demonstrate the importance of O(2) (-) generation and role of possible pathways in hemocyte mediated cellular immune response of a crustacean.