Ramar Manikandan

Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats.

The protective role of diallyl sulfide (DAS) in attenuating gentamicin-induced nephrotoxicity has been reported earlier. However, the mechanism of induction of antioxidants by DAS in nephrotoxicity remains elusive. This study is aimed to elucidate the role of a transcription factor, Nuclear factor E2-related factor 2 (Nrf2) in inducing antioxidants and phase II enzymes during gentamicin toxicity in Wistar rats. DAS was administered intraperitoneally at a dosage of 150 mg/kg body weight once daily for 6 days. Gentamicin was administered intraperitoneally at a dosage of 100 mg/kg body weight, once daily for 6 days. Gentamicin-induced rats showed a significant increase in the levels of kidney markers and the activities of urinary marker enzymes, which was reversed upon treatment with DAS. A significant increase in kidney myeloperoxidase (MPO) and lipid peroxidation (LPO) levels was observed in gentamicin-induced rats, which was reduced upon treatment with DAS. Gentamicin-induced rats also showed a significant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and quinone reductase (QR) in rat kidney, which was increased upon treatment with DAS. Immunohistochemical studies in gentamicin-induced rats demonstrated a marked increase in the immunoreactivity of inducible nitric oxide synthase (iNOS), nuclear transcription factor (NF-kappaB) and tumor necrosis factor alpha (TNF-alpha) that were reduced after treatment with DAS. Further, the involvement of Nrf2 in antioxidant induction was analyzed by Western blot and immunofluorescence. To conclude, DAS enhances antioxidants and suppresses inflammatory cytokines through the activation of Nrf2, thereby protecting the cell against oxidative stress induced by gentamicin.

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.

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.

Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-β activation: A biphasic experimental study

Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating and fatal lung disorder with high mortality rate. Unfortunately, to date the treatment for IPF remains unsatisfying and in severe cases lung transplantations are performed as a therapeutic measure. Thus, it becomes great interest to find novel agents to treat IPF. Berberine, a plant alkaloid known for its broad pharmacological activities remains a remedy against multiple diseases. This study was hypothesized to investigate the antifibrotic potential of berberine against bleomycin-induced lung injury and fibrosis, a tentative animal model. Male wistar rats were subjected to single intratracheal instillation of 2.5 U/kg of bleomycin on day 0. Berberine treatments were either provided in preventive or therapeutic mode respectively. Berberine administration significantly ameliorated the bleomycin mediated histological alterations and reduced the inflammatory cell infiltrate in BALF. Berberine significantly blocked collagen accumulations with parallel reduction in the hydroxyproline level. The immunological sign of bleomycin stimulated mast cell deposition and histamine release were considerably reduced by berberine. Berberine enhanced the antioxidant status, through upregulating the redox sensing transcription factor nuclear factor E2-related factor 2 (Nrf2). Berberine inhibited the bleomycin mediated activation of inflammatory mediator nuclear factor kappa B (NF-κB) and suppressed its downstream target inducible nitric oxide synthase (iNOS). Strikingly, berberine exhibited target attenuation of tumor necrosis factor alpha (TNF-α) and key pro-fibrotic mediator, transforming growth factor beta 1 (TGF-β1). Taken together, this study reveals the beneficial effects of berberine against bleomycin mediated fibrotic challenge through activating Nrf2 and suppressing NF-κB dependent inflammatory and TGF-β1 mediated fibrotic events.

Antioxidants and cataract

Abstract The major causes for cataract formation are free radicals, and these free radicals are neutralized by the presence of endogenous antioxidants in the eye. Using xenobiotics, it has been confirmed that free radicals mediate the formation of cataract. Two cataract model-selenite model and the diabetic cataract model-have been developed to study the pathophysiology of cataract formation due to free radicals and the role of antioxidants during the process of cataractogenesis. This review focuses on natural compounds with antioxidant properties that could actually be applied as an interventional strategy on a large scale and are also relatively inexpensive. A brief overview of plants with antioxidant properties that in addition possess potential anti-cataract properties has been discussed. In addition to plants, three natural compounds (curcumin, vitamin C and vitamin E), on which a lot of data exist showing anti-cataract and antioxidant activities, have also been discussed. These antioxidants can be supplemented in the diet for a better defence against free radicals. Studies on vitamin C and vitamin E have proved that they are capable of preventing lipid peroxidation, thereby preventing the generation of free radicals, but their efficacy as anti-cataract agent is questionable. Unlike vitamins C and E, curcumin is well established as an anti-cataract agent, but the issue of curcumin bioavailability is yet to be addressed. Nanotechnology proves to be a promising area in increasing the curcumin bioavailability, but still a lot more research needs to be done before the use of curcumin as an effective anti-cataract agent for humans.

Anti-cataractogenic effect of curcumin and aminoguanidine against selenium-induced oxidative stress in the eye lens of Wistar rat pups: an in vitro study using isolated lens.

The aim of this study was to investigate whether curcumin and aminoguanidine (AG) prevent selenium-induced cataractogenesis in vitro. On postpartum day 8, transparent isolated lens were incubated in 24 well plates containing Dulbeccos Modified Eagle Medium (DMEM). Isolated lens of group I were incubated with DMEM medium alone. Group II: lenses incubated in DMEM containing 100microM sodium selenite; group III: lenses incubated in DMEM containing 100microM sodium selenite and 100microM curcumin; group IV: lenses incubated in DMEM containing 100microM sodium selenite and 200microM curcumin; group V: lenses incubated in DMEM containing 100microM sodium selenite and 100microM AG; group V: lenses incubated in DMEM containing 100microM sodium selenite and 200microM AG. On day 12, cataract development was graded using an inverted microscope and the lenses were analyzed for enzymic as well as non-enzymic antioxidants, lipid peroxidation (LPO), nitric oxide (NO), superoxide anion (O(2)(-)) and hydroxyl radical generation (OH) and inducible nitric oxide synthase (iNOS) activity by Western blotting and RT-PCR. All control lenses in group I were clear (0). In groups II and III, all isolated lenses developed cataract with variation in levels (+++ or ++), whereas isolated lenses from groups IV, V and VI were clear (0). In agreement to this, a decrease in antioxidants and increased free radical generation and also iNOS expression were observed in selenium exposed lenses when compared to other groups. AG (100microM) was found to be more effective in anti-cataractogenic effect than curcumin (200microM). Curcumin and AG suppressed selenium-induced oxidative stress and cataract formation in isolated lens from Wistar rat pups, possibly by inhibiting depletion of enzymic as well as non-enzymic antioxidants, and preventing uncontrolled generation of free radicals and also by inhibiting iNOS expression. Our results implicate a major role for curcumin and AG in preventing cataractogenesis in selenite-exposed lenses, wherein AG was found to be more potent.

Biosynthesis of silver nanoparticles using ethanolic petals extract of Rosa indica and characterization of its antibacterial, anticancer and anti-inflammatory activities.

The present study was aimed at biosynthesis of silver nanoparticles (AgNPs) using ethanolic extract of rose (Rosa indica) petals and testing their potential antibacterial activity using selective human pathogenic microbes, anticancer activity using human colon adenocarcinoma cancer cell line HCT 15 as well as anti-inflammatory activity using rat peritoneal macrophages in vitro. The biologically synthesized AgNPs were also characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). The characterized AgNPs showed an effective antibacterial activity against Gram negative (Escherichia coli, Klebsiella pneumoniae) than Gram positive (Streptococcus mutans, Enterococcus faecalis) bacteria. MTT assay, analysis of nuclear morphology, mRNA expression of Bcl-2, Bax and protein expression of caspase 3 as well as 9, indicated potential anticancer activity. In addition, green synthesized AgNPs also attenuated cytotoxicity, nuclear morphology and free radical generation (O2(-) and NO) by rat peritoneal macrophages in vitro. The results of our study show the potential green synthesis of silver nanoparticles in mitigating their toxicity while retaining their antibacterial activities.

Phytochemical mediated gold nanoparticles and their PTP 1B inhibitory activity

Current discovery demonstrates the rapid formation of gold nanoparticles with guavanoic acid a phytochemical of Psidium guajava (Pg). The pharmacological capabilities of the phytochemicals present in the leaves of Pg and their ability to generate gold nanoparticles is presented herein. The new genre of green nanoparticles exhibit remarkable Protein Tyrosine Phosphatase 1B (PTP 1B) inhibitory activity and in vitro stability in various physiological medium including saline, histidine, cysteine, bovine serum albumin (BSA), human serum albumin (HSA) and buffers (pH 5, 7 and 9). It is predicted that this new technology will be felt greatly in several routes of pharmaceuticals.

Effect of Curcumin on Selenite-Induced Cataractogenesis in Wistar Rat Pups

Purpose: The present study was aimed at investigating the possible antioxidant potential of curcumin at a dose of 75 mg/kg body weight on selenite-induced cataract in experimental rat pups. Methods: Group I: Control rat pups receiving physiological saline; Group II: Selenite-induced group (15 µM/kg body wt); Group III: Selenite-induced group co-treated with curcumin (single dose of curcumin orally 75 mg/kg body wt); Group IV: Selenite-induced animals post-treated (after 24 hrs) with curcumin at a dose mentioned for group III; Group V: Rat pups were pretreated with curcumin (dose as mentioned in Group III), 24 hrs before the administration of selenite. Encapsulated lenses liver, kidney, and serum were analyzed for antioxidant enzymes and malondialdehyde, a marker of lipid peroxidation. Results: Intraperitoneal injection of sodium selenite (15 µM/kg body wt) to 8–10-day-old rat pups led to severe oxidative stress in eye lens as evidenced by enhanced LPO levels that led to cataract formation. Sodium selenite also led to decrease in activities of SOD, GST, GPx, CAT with simultaneous decrease in the levels of GSH, vitamin C, and vitamin E. Treatment with curcumin (75 mg/kg body wt) led to a significant decrease in the levels of LPO, enzymic antioxidants, and nonenzymic antioxidants, which were similar to that of control. Conclusions: Curcumin suppressed selenite-induced oxidative stress and cataract formation in rat pups. The presence of oxidative stress in selenite cataract development and its prevention by curcumin support the possibility that the natural consumption of curcumin in food can help prevent the onset of senile cataract.

Synergistic anticancer activity of curcumin and catechin: An in vitro study using human cancer cell lines

The most practical approach to reduce morbidity and mortality of cancer is to delay the process of carcinogenesis by usage of anticancer agents. This necessitates that safer compounds are to be critically examined for anticancer activity especially, those derived from natural sources. A spice commonly found in India and the surrounding regions, is turmeric, derived from the rhizome of Curcuma longa and the major active component is a phytochemical termed curcumin. Green tea is one of the most popular beverages used worldwide, produced from the leaves of evergreen plant Camellia sinensis and the major active ingredients are polyphenolic compounds known as catechins. In this study, synergistic anticancer activity of curcumin and catechin was evaluated in human colon adenocarcinoma HCT 15, HCT 116, and human larynx carcinoma Hep G‐2 cell lines. Although, both curcumin or catechin inhibited the growth of above cell lines, interestingly, in combination of both these compounds highest level of growth control was observed. The anticancer activity shown is due to cytotoxicity, nuclear fragmentation as well as condensation, and DNA fragmentation associated with the appearance of apoptosis. These results suggest that curcumin and catechin in combination can inhibit the proliferation of HCT 15, HCT 116, as well as Hep G‐2 cells efficiently through induction of apoptosis. Microsc. Res. Tech., 2011.