Pretreatment of Tribulus terrestris L. causes anti-ischemic cardioprotection through MAPK mediated anti-apoptotic pathway in rat.

The aim of the present investigation is the evaluation and elucidation of the mechanisms by which Tribulus terrestris L. methanol extract (TTM) devoid of fruit exhibits protection against cardiac ischemia in in vitro (H9c2 cell line) and in vivo (Wistar rat) model. Tribulus terrestris L. (TT) was used in this study to evaluate the efficacy against cardiac ischemia employing in vitro and in vivo models of myocardial ischemia. H9c2 cells were used for the in vitro induction of ischemia. Male Wistar rats (10 weeks old) weighing 180-220 g were used for the in vivo experiments. ECG and clinically relevant cardiac biomarkers like serum lactate dehydrogenase, serum creatinine kinase, serum creatinine kinase myocardial B fraction, serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase were analysed to evaluate efficacy in the rat. For elucidation of molecular mechanisms of its beneficial activity in vitro, expression of apoptotic markers like Bax, Bad, Bcl-2 and signalling pathways involving mitogen-activated protein kinases like p38α, JNK, and Akt were studied. Tribulus terrestris L. was found effective against cardiac ischemia in the rat which was evident from ECG and various cardiac biomarkers analysis. Tribulus terrestris L. was found to act through the mitogen-activated signalling pathway leading to prevention of apoptosis during ischemic insult. The beneficial effect of Tribulus terrestris L. against cardiac ischemia was seen both in in vitro and in vivo models via its anti-apoptotic potential.

Eugenol, a plant-derived phenolic nutraceutical, protects thiol (SH) group in myocardium from ROS-mediated oxidation under chemotherapeutic stress induced by arsenic trioxide - a in vivo model study.

Arsenic trioxide is an effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. The clinical usefulness of arsenic trioxide is narrow due to different organ toxicities. It is hypothesized that the generation of reactive oxygen species by arsenic trioxide leads to thiol-based oxidative damage in rat myocardium. In this study, the defensive effect of eugenol on thiol-based oxidative stress was investigated in arsenic trioxide-treated rats. Rats were orally administered with arsenic trioxide (4 mg/kg per day) alone and in combination with eugenol (5 mg/kg per day) for 30 days. Reduction in relative organ weight, total thiol level, protein thiol content, acid-soluble thiol content, thioredoxin activity, and protein content was witnessed in arsenic trioxide-treated rats. Additionally, the total antioxidant activity, tissue GSH level, and GSH/GSSG ratio were considerably diminished. However, the co-treatment of eugenol noticeably sheltered the arsenic trioxide-mediated cardiotoxicity. In conclusion, eugenol is a prospective phenolic compound, of natural origin, for protecting the thiol group in myocardium from oxidative stress by chemotherapeutic compounds.

Attenuation of arsenic trioxide induced cardiotoxicity through flaxseed oil in experimental rats.

OBJECTIVES: Arsenic trioxide (As2O3) is a potent drug for acute promyelocytic leukaemia, but its clinical trials are allied with some serious adverse events mainly cardiac functional abnormalities. So the objective of our investigation is to identify the cardioprotective action of flaxseed oil (FSO), a natural compound against As2O3 induced cardiotoxicity. METHODS: Male wistar rats were treated with As2O3 (4 mg/kg) to induce cardiotoxicity. FSO (250 and 500 mg/kg) was given in combination with As2O3 for evaluating its cardioprotective efficacy. RESULTS: Treatment with As2O3 resulted in deposition of arsenic in heart tissue, increased cardiac marker enzymes release, lipid peroxidation (LPO), oxidative insults and pathological damages in the heart. Co-treatment with FSO (500 mg/kg) significantly reduced the arsenic accumulation, cardiac marker enzymes, LPO and cardiac structural alterations. FSO treatment significantly improved cardiac glutathione content, antioxidant enzymes and reduced the pathological damages in cardiac tissue. Gas chromatographic-mass spectrometry analysis revealed that the major fatty acid content in the FSO is alpha-linolenic acid, which has a strong milieu in cardiac health. CONCLUSION: The results of the current investigation suggested that FSO is an effective agent in reducing arsenic-induced cardiac toxicity and can be used as an adjunct/dietary supplement for the cancer patients on As2O3 therapy.

Polyphenol rich ethanolic extract from Boerhavia diffusa L. mitigates angiotensin II induced cardiac hypertrophy and fibrosis in rats.

Boerhavia diffusa is a renowned edible medicinal plant extensively used against different ailments including heart diseases in the traditional system of medicine in several countries. The present study aims to evaluate the therapeutic efficacy of ethanolic extract of Boerhavia diffusa (BDE) on cardiac hypertrophy and fibrosis induced by angiotensin II (Ang II) in male wistar rats and to identify the active components present in it. A substantial increase of hypertrophy markers such as cardiac mass index, concentration of ANP and BNP, cardiac injury markers like CK-MB, LDH and SGOT, has been observed in hypertrophied groups whereas BDE treatment attenuated these changes when compared to hypertrophied rats. Moreover, Ang II induced myocardial oxidative stress was reduced by BDE which was apparent from diminished level of lipid and protein oxidation products, increased activities of membrane bound ATPases and endogenous antioxidant enzymes along with enhanced translocation of Nrf2 from the cytosol to nucleus. It appears that BDE evokes its antioxidant effects by attenuating lipid peroxidation, enhancing the translocation of Nrf2 from the cytoplasm to nucleus as well as by regulating the metabolism of glutathione. The extent of fibrosis during cardiac hypertrophy was determined by histopathology analysis and the results revealed that BDE treatment considerably reduced the fibrosis in the heart. HPLC analysis of BDE leads to the identification of four compounds viz., quercetin, kaempferol, boeravinone B and caffeic acid. The study substantiate the effect of B. diffusa in protecting the heart from pathological hypertrophy and the attenuation of cardiac abnormalities may be partly attributed through the reduction of oxidative stress and cardiac fibrosis. Since the plant is widely used as a green leafy vegetable, incorporation of this plant in diet may be an alternative way for the prevention and better management of heart diseases and associated complications.

Omega-3 Fatty Acid Protects Against Arsenic Trioxide-Induced Cardiotoxicity In Vitro and In Vivo.

Arsenic trioxide (As2O3) is a highly effective therapeutic against acute promyelocytic leukaemia, but its clinical efficacy is burdened by serious cardiac toxicity. The present study was performed to evaluate the effect of omega (ω)-3 fatty acid on As2O3-induced cardiac toxicity in in vivo and in vitro settings. In in vivo experiments, male Wistar rats were orally administered with As2O3 4 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. As2O3 significantly increased the tissue arsenic deposition, micronuclei frequency and creatine kinase (CK)-MB activity. There were a rise in lipid peroxidation and a decline in reduced glutathione, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase in heart tissue of arsenic-administered rats. The cardioprotective role of ω-3 fatty acid was assessed by combination treatment with As2O3. ω-3 fatty acid co-administration with As2O3 significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, As2O3 treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (∆Ψm). ω-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ∆Ψm. These findings suggested that the ω-3 fatty acid has the potential to protect against As2O3-induced cardiotoxicity.

Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain.

Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.

Astaxanthin modulates osteopontin and transforming growth factor ß1 expression levels in a rat model of nephrolithiasis: a comparison with citrate administration.

OBJECTIVES: To evaluate the effect of astaxanthin on renal angiotensin-I converting enzyme (ACE) levels, osteopontin (OPN) and transforming growth factor ß1 (TGF-ß1) expressions and the extent of crystal deposition in experimentally induced calcium oxalate kidney stone disease in a male Wistar rat model. To compare the efficacy of astaxanthin treatment with a currently used treatment strategy (citrate administration) for kidney stones. MATERIALS AND METHODS: The expression of OPN was assessed by immunohistochemistry. One step reverse transcriptase polymerase chain reaction followed by densitometry was used to assess renal OPN and TGF-ß1 levels. Renal ACE levels were quantified by an enzyme-linked immunosorbent assay method. Crystal deposition in kidney was analysed by scanning electron microscopic (SEM)-energy-dispersive X-ray (EDX). RESULTS: The renal ACE levels and the expression of OPN and TGF-ß1 were upregulated in the nephrolithiasis-induced rats. Astaxanthin treatment reduced renal ACE levels and the expression OPN and TGF-ß1. SEM-EDX analysis showed that crystal deposition was reduced in the astaxanthin-treated nephrolithiatic group. Astaxanthin treatment was more effective than citrate administration in the regulation of renal ACE levels, OPN and TGF-ß1 expressions. CONCLUSIONS: Astaxanthin administration reduced renal calcium oxalate crystal deposition possibly by modulating the renal renin-angiotensin system (RAS), which reduced the expression of OPN and TGF-ß1 levels. Astaxanthin administration was more effective than citrate treatment in reducing crystal deposition and down-regulating the expression of OPN and TGF-ß1.

Mitigation of hepatotoxic effects of arsenic trioxide through omega-3 fatty acid in rats.

Arsenic trioxide (As(2)O(3)) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As(2)O(3)-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As(2)O(3) was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As(2)O(3). Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As(2)O(3). In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As(2)O(3) offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As(2)O(3)-induced hepatotoxicity.

Oxidative stress induced by the chemotherapeutic agent arsenic trioxide.

Arsenic compounds have been used for medicinal purposes throughout history. Arsenic trioxide (As2O3) achieved dramatic remissions in patients with acute promyelocytic leukaemia. Unfortunately, the clinical usefulness of As2O3 has been limited by its toxicity. The present study was designed to investigate the toxic effects of As2O3 at its clinical concentrations. Experimental rats were administered with As2O3 2, 4 and 8 mg/kg body weight for a period of 45 days and the serum glucose, creatine kinase, lactate dehydrogenase, lipid peroxidation and antioxidant status were measured. As2O3-treated rats showed elevated serum glucose, creatine kinase and lactate dehydrogenase concentrations. Lipid peroxidation product malondialdehyde was found to be produced more in arsenic-treated rats. Reduced glutathione and glutathione-dependant antioxidant enzymes, glutathione-S-transferase and glutathione peroxidase, and the antiperoxidative enzymes, superoxide dismutase and catalase, concentrations were reduced with the As2O3 treatment. All these toxic effects were found increased with the increase in concentration of As2O3. The results of the study indicate that As2O3 produced dose-dependant toxic side effects at its clinical concentrations.

Long-term consumption of aspartame and brain antioxidant defense status.

The present study investigated the effect of long-term intake of aspartame, a widely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistar rats weighing 150-175 g were randomly divided into three groups as follows: The first group was given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL of water; and the control rats received 3 mL of distilled water. Oral intubations were done in the morning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activity of glutathione reductase (GR) were significantly reduced in the brain of rats that had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSH concentration was observed in the 500-mg/kg b.w. aspartame-treated group. Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results of this experiment indicate that long-term consumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathione-dependent system.

Protective effects of α-tocopherol against oxidative stress related to nephrotoxicity by monosodium glutamate in rats.

CONTEXT: Chronic oral intake of high doses of monosodium glutamate (MSG) could be harmful to tissues and organs. Oxidative stress enhances membrane damage by lipid peroxidation and alterations of antioxidant enzymes, which affects the functional activity of organs. Antioxidant vitamins have the capacity to regulate the oxidative stress related functional and pathological processes. OBJECTIVE: In this study, the protective role of α-tocopherol against MSG-induced nephrotoxicity was analyzed. MATERIALS AND METHODS: MSG (4 g/kg) was given orally to female wistar rats for a period of 180 days. Renal function parameters (urea, uric acid, and creatinine), lipid peroxidation markers (malondialdehyde and conjugated dienes), antioxidant system (superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, and reduced glutathione), and histopathology were investigated. All tests were done in rats treated with MSG and at two different doses of α-tocopherol (100 and 200 mg/kg). RESULTS: Oral exposure of MSG significantly increased renal function markers, lipid peroxidation byproducts, and altered antioxidant system. Moreover, the kidney showed congested glomeruli, tubular swelling, capillary congestion and microhemorrhages in stromal areas of the tubules. Co-administration of MSG and α-tocopherol (200 mg/kg) significantly reduced the oxidative damage compared with MSG-treated group and also restored the normal renal function. DISCUSSION: The results indicated that oxidative stress was involved in MSG-induced functional and pathological changes in the kidney. α-tocopherol modulates the functional disorder and maintains the normal architecture of renal tissue by reducing oxidative stress. CONCLUSION: The α-tocopherol may be a potent protective agent in combating MSG-induced renal toxicity.

Effect of long term intake of aspartame on antioxidant defense status in liver.

The present study evaluates the effect of long term intake of aspartame, the artificial sweetener, on liver antioxidant system and hepatocellular injury in animal model. Eighteen adult male Wistar rats, weighing 150-175 g, were randomly divided into three groups as follows: first group was given aspartame dissolved in water in a dose of 500 mg/kg b.wt.; the second group was given a dose of 1000 mg/kg b.wt.; and controls were given water freely. Rats that had received aspartame (1000 mg/kg b.wt.) in the drinking water for 180 days showed a significant increase in activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT). The concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), and glutathione reductase (GR) were significantly reduced in the liver of rats that had received aspartame (1000 mg/kg b.wt.). Glutathione was significantly decreased in both the experimental groups. Histopathological examination revealed leukocyte infiltration in aspartame-treated rats (1000 mg/kg b.wt.). It can be concluded from these observations that long term consumption of aspartame leads to hepatocellular injury and alterations in liver antioxidant status mainly through glutathione dependent system.

Respiratory functions in Kalaripayattu practitioners.

Kalaripayattu, an ancient traditional martial art form of Kerala, is considered as the basis for all martial arts viz. Karate, Kungfu, etc. physiological studies are more concentrated on Karate, Kungfu and other martial arts due to their global acceptance. Considering the limited knowledge available regarding the physiological profiles of Kalaripayattu practitioners, the present study was taken up for filling the lacunae in the field. Lung function tests were carried out in ten Kalari practitioners. Residual volume was measured by indirect method. Higher lung volumes and flow rates were achieved in Kalari practitioners compared to age and height-matched controls. Better mechanical factors and lower airway resistance influenced during Kalari practice might have benefited in improving hung volumes and flow rates.