Effect of Alpha lipoic acid on cadmium induced oxidative damage on heart, brain, kidney, liver and lung of rats

En el presente estudio se investigó el efecto protector del ácido alfa lipoico (ALA) sobre el daño oxidativo inducido por el cadmio en ratas. El cadmio (100 ppm) suministrado a ratas normales dio lugar a un aumento significativo de los niveles de transaminasa glutámico-oxalacética sérica (SGOT), transaminasa glutámico-pirúvica sérica (SGPT) y fosfatasa alcalina (ALP). En los animales expuestos al cadmio se observó igualmente un aumento significativo del nivel de peroxidación lipídica (LPO) y una disminución de los niveles de glutatión reducido (GSH), superóxido dismutasa (SOD), catalasa (CAT) y ATPasas de la membrana (Na+K+-ATPasa, Ca2+-ATPasa y Mg2+-ATPasa) en cerebro, pulmón, riñón, hígado y corazón en comparación con el grupo de control. La administración conjunta de ALA (25mg/kg/día, i.p.) y cadmio durante treinta días dio lugar a una disminución significativa de los niveles de SGOT, SGPT y fosfatasa alcalina en suero hasta niveles cercanos a los normales. El uso de ALA también supuso una reducción del nivel de MDA y un aumento de los niveles de SOD, CAT, GSH y ATPasas unidas a la membrana en todos los órganos de los animales tratados con cadmio hasta niveles cercanos a los normales. El presente estudio demuestra el daño inducido por radicales libres derivados de la administración de cadmio sobre distintos órganos y el efecto antioxidante del ALA que protege a los órganos frente a este daño cuando se administra conjuntamente con cadmio.This study investigated the protective effect of alpha lipoic acid (ALA) on cadmium induced oxidative damage in rats. Cadmium (100ppm) fed to normal rats resulted in signifi cant increase in the level of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and Alkaline Phosphatase (ALP). Animals exposed to cadmium also showed a signifi cant increase in level of lipid peroxidation (LPO) and decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD) , catalase (CAT) and membrane bound ATPases (Na+K+ATPase, Ca2+ATPase and Mg2+ATPase) in brain, lung, kidney, liver and heart as compared to control group. Coadministration of ALA (25mg/kg/day, i.p.) along with cadmium for thirty days significantly decreased the levels of SGOT, SGPT and Alkaline Phosphatase in the serum to near normal levels. ALA also reduced the level of MDA and increased the levels of SOD, CAT, GSH and membrane bound ATPases in all the organs of the animals treated with cadmium to near normal levels. This study demonstrates the free radical damage caused by administration of cadmium on different organs and the antioxidant effect of ALA which protects the organs from this damage when it is given along with cadmium

BIOAVAILABILITY ENHANCEMENT OF POORLY SOLUBLE RALOXIFENE BY DESIGNING INCLUSION COMPLEX WITH β–CYCLODEXTRIN

Objective: Raloxifene hydrochloride (RLX) is widely used in the treatment of osteoporosis, but due to its extensive first pass metabolism bioavailability of RLX is remaining only 2%. In addition of that being from BCS class II, RLX has poor water solubility. Therefore the objective of present research work was to enhance solubility and dissolution rate of RLX by formulating inclusion complex with β cyclodextrin (β-CD) as a carrier.Methods: Inclusion complex was prepared by various methods like physical mixture, co-precipitation method and kneading method using different drug to carrier ratios (1:1, 1:2 and 1:3).Results: Inclusion complex prepared with co-precipitation method had shown 5.5 fold improvements in water solubility and significant increment in dissolution rate when compared with plain RLX. Optimized formulation was characterized by Fourier transform infrared spectroscopy, Differential scanning calorimetry, X-ray diffraction and Scanning electron microscopy studies for their compatibility, thermal analysis, crystallinity and surface morphology determination, respectively. Results of DSC and XRD study suggested the conversion of RLX from crystalline form to amorphous form. Stability studies showed stable formulation up to the period of 6 months. In vivo pharmacokinetic study was also conducted in wistar rats for optimized drug loaded inclusion complex that showed nearby two fold increments in drug bioavailability compared to plain drug suspension.Conclusion: From these studies, it can be concluded that solubility and dissolution rate of poorly soluble raloxifene could be remarkably increased by formulating into the inclusion complex with β-CD which results in significant improvement in bioavailability of poorly soluble RLX.Â

Reactivity ratio estimation in copolymerization: a new analysis of unresolved conflicts

Using a stochastic approach, a fresh analysis has been provided to resolve the possible causes of the existing conflicts in the reactivity ratio estimation in copolymerization systems. The analysis provides some new clues regarding the inadequacy of a transient system (batch reactor) and suggests the use of a steady state operation (CSTR) as a more reliable method

Effect of green tea extract on cisplatin induced oxidative damage on kidney and testes of rats

Se administró extracto de té verde (Camellia sinensis) por vía oral a las ratas en dosis de 25, 50 y 100 mg/kg para investigar sus efectos sobre la nefrotoxicidad y la toxicidad testicular inducida por cisplatino (3mg/kg). El extracto de té verde restauró el nivel de creatinina, urea, nitrógeno ureico en sangre (NUS) y ácido úrico en el suero de animales tratados con cisplatino en comparación con los animales tratados sólo con cisplatino. Además, se observó que la administración de extracto de té verde restauró los niveles de enzimas antioxidantes como superóxido dismutasa (SOD), catalasa (CAT) y glutatión reducido (GSH), y enzimas ligadas a la membrana como Na+K+ATPasa, Ca2+ATPasa y Mg2+ATPasa y redujo la peroxidación lipídica (MDA) en los riñones y en los testículos de animales con alteraciones tras el tratamiento crónico con cisplatino. Por tanto, se puede concluir que el extracto de té verde posee actividad antioxidante y que, en virtud de esta acción, puede proteger los riñones y los testículos frente a los daños oxidativos inducidos por el cisplatino.Green tea extract (Camellia sinensis) was administered orally to rats at the dose levels of 25, 50,100 mg/kg to investigate its effect on cisplatin (3mg/kg) induced nephrotoxicity and testicular toxicity. Green tea extract restored the level of creatinine, urea, blood urea nitrogen (BUN) and uric acid in serum of animals treated with cisplatin as compared to the animals treated with cisplatin alone. It was further found that administration of green tea extract restored the level of antioxidant enzymes such as, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), and membrane bound enzymes like Na+K+ATPase, Ca2+ATPase and Mg2+ATPase and decreased lipid peroxidation (MDA) in kidney and in testes of animals which were altered after chronic treatment with cisplatin. Thus it can be concluded that green tea extract possesses antioxidant activity and by virtue of this action it can protect the kidney and testes from cisplatin induced oxidative damage

Antioxidant activity of activit, a herbomineral formulation, in experimentally induced cardiac and renal damage

Se administró Activit, una formulación herbomineral, a ratas por vía oral en dosis de 125, 250, 500 y 1000 mg kg- 1 para investigar sus efectos en infartos de miocardio inducidos mediante isoproterenol y daños renales inducidos mediante cisplatina. El fármaco redujo los niveles de glutamato oxaloacetato transaminasa (GOT), lactato dehidrogenasa (LDH), ácido úrico y de creatina kinasa (CK)en el suero en casos de daño cardíaco inducido mediante isoproterenol. En los casos de daño renal inducido mediante cisplatina, Activit redujo los niveles séricos de creatinina, urea, nitrógeno ureico en sangre (NUS) y ácido úrico. Se descubrió además que la administración de Activit aumentó los niveles de superóxido dismutasa (SOD), catalasa (CAT); glutatión reducido (GSH) y enzimas ligadas a la membrana tales como la Ca2+ATPasa y Na+K+ATPasa, y redujo la peroxidación lipídica (MDA) en el riñón y en el corazón en los casos de daño renal inducidos mediante cisplatina y en los de necrosis miocárdica inducida mediante isoproterenol, respectivamente. Por tanto, se puede concluir que Activit posee actividad antioxidante y que, en virtud de esa acción, puede proteger el corazón y el riñón de los daños causados por el isoproterenol y la cisplatina, respectivamente.Activit, a herbomineral formulation, was administered orally to rats at the dose levels of 125, 250, 500 and 1000 mg kg- 1 to investigate its effect on isoproterenol-induced myocardial infarction and cisplatin-induced renal damage. The drug reduced the levels of serum creatine kinase (CK), glutamic oxaloacetate transaminase (GOT), lactate dehydrogenase (LDH) and uric acid in isoproterenol-induced cardiac damage. In cisplatin-induced renal damage, Activit reduced the serum levels of creatinine, urea, blood urea nitrogen (BUN) and uric acid. It was further found that administration of Activit increased the levels of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and membrane bound enzymes like Ca2+ATPase, Mg2+ATPase and Na+K+ATPase and decreased lipid peroxidation (MDA) in heart and kidney in isoproterenol-induced myocardial necrosis and cisplatin-induced renal damage, respectively. Thus it can be concluded that Activit possesses antioxidant activity and by virtue of this action it can protect the heart and kidney from damage caused by isoproterenol and cisplatin, respectively.Este trabajo ha sido financiado por la UGC

Hemidesmus indicus and Hibiscus rosa-sinensis Affect Ischemia Reperfusion Injury in Isolated Rat Hearts

Hemidesmus indicus (L.) R. Br. (HI) and Hibiscus rosa-sinensis L. (HRS) are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R). Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure), reperfusion arrhythmias, and infarct size (TTC staining) served as the endpoints. A transient increase in LVDP (32%–75%) occurred at all concentrations of HI, while coronary flow (CF) was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55%) and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions

EFFECT OF COENZYME Q10 ALONE AND ITS COMBINATION WITH ROSUVASTATIN ON STREPTOZOTOCIN-NICOTINAMIDE INDUCED DIABETIC NEUROPATHY IN RATS

Objectives: This study was aimed to investigate the effect of coenzyme Q10 and its combination with rosuvastatin on STZ-nicotinamide induced diabetic neuropathy.Methods: Diabetic neuropathy in rats were induced with streptozotocin-nicotinamide. The diabetic rats were treated with coenzyme Q10 or rosuvastatin or their combination. Various parameters like muscular grip strength, paw withdrawal response, tail flick response and markers of oxidative stress such as malondialdehyde (MDA) level, superoxide dismutase (SOD) and reduced glutathione (GSH) in the sciatic nerve were measured. All treated animal was subjected to histopathological changes of sciatica nerve.Results: In diabetic control group, muscular grip strength was significantly decreased and increased paw withdrawal response, tail flick response as compared to normal control rats. In addition, STZ-nicotinamide caused nerve cell damage with a higher MDA level, depletion of SOD and GSH level along with marked degeneration of the nerve cell. The treatment of diabetic rats with coenzyme Q10 or rosuvastatin or their combination ameliorate STZ-nicotinamide induced nerve damage due to improvement in the muscular grip strength, paw withdrawal response, tail flick response, reduction in oxidative stress along with histopathological changes.Conclusion: This finding suggests that treatment with coenzyme Q10 or rosuvastatin showed significant neuroprotective effect against STZ-nicotinamide induced diabetic neuropathy. However, concomitant administration of both showed a better neuroprotective effect than coenzyme Q10 or rosuvastatin alone treatment.Â

Efecto del ácido alfa lipoico sobre el daño oxidativo inducido por cadmio en corazón, cerebro, riñón, hígado y pulmón de ratas

This study investigated the protective effect of alpha lipoic acid (ALA) on cadmium induced oxidative damage in rats.Cadmium (100ppm) fed to normal rats resulted in signifi cant increase in the level of serum glutamate oxaloacetatetransaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and Alkaline Phosphatase (ALP). Animalsexposed to cadmium also showed a signifi cant increase in level of lipid peroxidation (LPO) and decreased levels of reducedglutathione (GSH), superoxide dismutase (SOD) , catalase (CAT) and membrane bound ATPases (Na+K+ATPase,Ca2+ATPase and Mg2+ATPase) in brain, lung, kidney, liver and heart as compared to control group. Co administrationof ALA (25mg/kg/day, i.p.) along with cadmium for thirty days signifi cantly decreased the levels of SGOT, SGPT andAlkaline Phosphatase in the serum to near normal levels. ALA also reduced the level of MDA and increased the levels ofSOD, CAT, GSH and membrane bound ATPases in all the organs of the animals treated with cadmium to near normallevels. This study demonstrates the free radical damage caused by administration of cadmium on different organs andthe antioxidant effect of ALA which protects the organs from this damage when it is given along with cadmium.En el presente estudio se investigó el efecto protector del ácido alfa lipoico (ALA) sobre el daño oxidativo inducidopor el cadmio en ratas. El cadmio (100 ppm) suministrado a ratas normales dio lugar a un aumento signifi cativode los niveles de transaminasa glutámico-oxalacética sérica (SGOT), transaminasa glutámico-pirúvica sérica (SGPT)y fosfatasa alcalina (ALP). En los animales expuestos al cadmio se observó igualmente un aumento signifi cativodel nivel de peroxidación lipídica (LPO) y una disminución de los niveles de glutatión reducido (GSH), superóxidodismutasa (SOD), catalasa (CAT) y ATPasas de la membrana (Na+K+-ATPasa, Ca2+-ATPasa y Mg2+-ATPasa) encerebro, pulmón, riñón, hígado y corazón en comparación con el grupo de control. La administración conjunta deALA (25mg/kg/día, i.p.) y cadmio durante treinta días dio lugar a una disminución signifi cativa de los niveles deSGOT, SGPT y fosfatasa alcalina en suero hasta niveles cercanos a los normales. El uso de ALA también supusouna reducción del nivel de MDA y un aumento de los niveles de SOD, CAT, GSH y ATPasas unidas a la membranaen todos los órganos de los animales tratados con cadmio hasta niveles cercanos a los normales. El presente estudiodemuestra el daño inducido por radicales libres derivados de la administración de cadmio sobre distintos órganosy el efecto antioxidante del ALA que protege a los órganos frente a este daño cuando se administra conjuntamentecon cadmio