Publications (23) View all
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Article: Insulin Resistance, Oxidative Stress and Cardiovascular Complications: Role of Sirtuins.
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ABSTRACT: Cardiovascular disease (CVD) is one of the major lifestyle associated disorders and leading causes of death worldwide. The incidence of CVD in diabetic patients has increased up to 3 folds and it became the major risk for diabetes associated morbidity and mortality. Insulin resistance and oxidative stress both play a central role in the pathogenesis and progression of diabetes. The high prevalence of CVD among diabetic patients suggests the role of insulin resistance and oxidative stress in developing cardiovascular complications. Finding molecular mechanisms which could control both insulin resistance and oxidative stress would be more efficacious in improving the cardiovascular complications. Recent literatures show that an epigenetic mechanism could control or regulate the cardiovascular complications in diabetes. Sirtuins, a group of enzymes, modulate epigenetic changes by deacetylating histone and non-histone proteins. These enzymes are distributed in different cell organelles and are found to regulate different biological processes. Recent findings showed that sirtuins modulate different important proteins related to insulin signaling pathway and oxidative stress. This review summarizes how sirtuins could affect the insulin resistance and oxidative stress pathways in cardiovascular system and thus attenuate the cardiovascular complications. Understanding the role of sirtuins in insulin resistance and oxidative stress will increase the prospects for controlling or preventing cardiovascular complications in the future.Current pharmaceutical design 02/2013; · 4.41 Impact Factor -
Article: Garlic as an Anti-diabetic agent: Recent Progress and Patent Reviews.
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ABSTRACT: This article reviews the use of garlic and its bioactive components for diabetes and discloses recent patents on the subject. Antidiabetic effect of garlic is well documented in ancient medical literatures. Garlic and its different preparations have been extremely studied in different animal models of diabetes. Human studies are also available where hypoglycaemic effect of garlic is reported. Beneficial effects of garlic are attributed due to the presence of volatile sulfur compounds like Alliin, Allicin, Diallyl disulfide, Diallyl trisulfide, diallyl sulfide, S-allyl cysteine, Azoene and Allyl mercaptan. Garlic and its different preparations are effective in reducing insulin resistance and diabetic complications in different organs. Considering garlic's importance in controlling diabetes and its complication, several preparations and food process containing garlic have been patented to prevent diabetes. The purpose of this review is to highlight the recent progress of garlic and its preparations in diabetes and translate these finding from laboratory to clinic.Recent patents on food, nutrition & agriculture. 12/2012; -
Article: In vivo metabolic investigation of moxifloxacin using liquid chromatography/electrospray ionization tandem mass spectrometry in combination with online hydrogen/deuterium exchange experiments.
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ABSTRACT: Tuberculosis is a leading cause of death from an infectious disease and moxifloxacin is an effective drug as compared to other fluoroquinolones. To date only two metabolites of the drug are known. Therefore, the present study on characterization of hitherto unknown in vivo metabolites of moxifloxacin using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) is undertaken. In vivo metabolites of moxifloxacin have been identified and characterized by using LC/ESI-MS/MS in combination with an online hydrogen/deuterium (H/D) exchange technique. To identify in vivo metabolites, blood, urine and faeces samples were collected after oral administration of moxifloxacin to Sprague-Dawley rats. The samples were prepared using an optimized sample preparation approach involving protein precipitation, liquid-liquid extraction followed by solid-phase extraction and LC/MS/MS analysis. A total of nine phase I and ten phase II metabolites of moxifloxacin have been identified in urine samples including N-sulphated, glucuronide and hydroxylated metabolites which are also observed in plasma samples. In faeces samples, only the N-sulphated metabolite is observed. The structures of metabolites have been elucidated based on fragmentation patterns, accurate mass measurements and online H/D exchange LC/MS/MS experiments. Online H/D exchange experiments are used to support the identification and structural characterization of drug metabolites. A total of 19 in vivo metabolites of moxifloxacin have been characterized using LC/ESI-MS/MS in combination with accurate mass measurements and online H/D exchange experiments. The main phase I metabolites of moxifloxacin are hydroxylated, decarbonylated, desmethylated and desmethylhydroxylated metabolites which undergo subsequent phase II glucuronidation pathways.Rapid Communications in Mass Spectrometry 08/2012; 26(16):1817-31. · 2.79 Impact Factor -
Article: Identification and structural characterization of in vivo metabolites of ketorolac using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS).
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ABSTRACT: In vivo metabolites of ketorolac (KTC) have been identified and characterized by using liquid chromatography positive ion electrospray ionization high resolution tandem mass spectrometry (LC/ESI-HR-MS/MS) in combination with online hydrogen/deuterium exchange (HDX) experiments. To identify in vivo metabolites, blood urine and feces samples were collected after oral administration of KTC to Sprague-Dawley rats. The samples were prepared using an optimized sample preparation approach involving protein precipitation and freeze liquid separation followed by solid-phase extraction and then subjected to LC/HR-MS/MS analysis. A total of 12 metabolites have been identified in urine samples including hydroxy and glucuronide metabolites, which are also observed in plasma samples. In feces, only O-sulfate metabolite and unchanged KTC are observed. The structures of metabolites were elucidated using LC-MS/MS and MS(n) experiments combined with accurate mass measurements. Online HDX experiments have been used to support the structural characterization of drug metabolites. The main phase I metabolites of KTC are hydroxylated and decarbonylated metabolites, which undergo subsequent phase II glucuronidation pathways.Biological Mass Spectrometry 07/2012; 47(7):919-31. · 3.41 Impact Factor -
Article: Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats.
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ABSTRACT: Metabolic syndrome and oxidative stress are common complications of type 2 diabetes mellitus. The present study was designed to determine whether resveratrol, a widely used nutritional supplement, can improve insulin sensitivity, metabolic complication as well as hepatic oxidative stress in fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four groups with 8 animals each. Fructose-fed insulin resistant group (Dia) animals were fed 65% fructose (Research diet, USA) for a period of 8 weeks, whereas control group (Con) animals were fed 65% cornstarch (Research Diet, USA). Resveratrol, 10 mg/kg/day (Dia+Resv) or metformin 300 mg/kg/day (Dia+Met) were administered orally to the 65% fructose-fed rats for 8 weeks. At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels. Significant (p<0.05) increase in hepatic TBARS and conjugated dienes, and significant (p<0.05) decrease in hepatic SOD and vitamin C was observed in Dia group compared to Con group. Administration of metformin or resveratrol significantly (p<0.05) normalized all the altered metabolic parameters. However, a marked insulin sensitizing action was only observed in the Dia+Resv group. Similarly, while metformin administration failed to normalize the increased TBARS levels and decreased SOD activity, resveratrol showed a more promising effect of all oxidative stress parameters measured in the present study. Attenuation of hepatic oxidative stress in fructose-fed rat liver after resveratrol administration was associated with significant (p<0.05) increase in nuclear level of NRF2 compared with other groups. The present study demonstrates that resveratrol is more effective than metformin in improving insulin sensitivity, and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.Pharmacological Research 05/2012; 66(3):260-8. · 4.44 Impact Factor
