Aman Upaganlawar

Cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats: A biochemical, electrocardiographic and histoarchitectural evaluation

The present study was designed to investigate the cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats by studying myocyte injury markers, antioxidant defense system, serum and heart lipid profile, inflammatory markers, electrocardiographic and histopathological changes. Male Sprague Dawley (SD) rats were randomly divided into four groups, namely control, melatonin, isoproterenol and melatonin+isoproterenol treated group. Melatonin treatment group received melatonin (10mg/kg/day, i.p.) for 7days. Myocardial infarction in rats was induced by isoproterenol administration (150mg/kg, s.c.) at an interval of 24h on 6th and 7th day. On 8th day ECG, gravimetric, biochemical and histopathological parameters were assessed. Isoproterenol administration showed changes in ECG pattern, including ST-segment elevation (diagnostic of myocardial infarction) increase in the serum levels of cardiac injury markers (creatine kinase-MB, lactate dehydrogenase, aspartate transaminase and alanine transaminase), decreased antioxidant defense system in the heart and altered lipid profile in the serum and heart. Isoproterenol administration also resulted in release of inflammatory markers and neutrophil infiltration along with histopathological changes. Melatonin pre-co-treatment prevented almost all the parameters of isoproterenol induced myocardial infarction in rats. The above finding was confirmed by the histopathological examination. In the baseline group (melatonin alone treated group) no significant change was observed. Results of the present study suggest that melatonin has a significant effect on the protection of the heart against isoproterenol induced myocardial infarction through maintaining endogenous antioxidant enzyme activities.

Adipocytokines: The pied pipers

Even though there have been major advances in therapy, atherosclerosis and coronary artery disease retain their lead as one of the major causes of morbidity and mortality in the first decade of 21st century. To add to the woes, we have diabetes, obesity and insulin resistance as the other causes. The adipose tissue secretes several bioactive mediators that influence inflammation, insulin resistance, diabetes, atherosclerosis and several other pathologic states besides the regulation of body weight. These mediators are mostly proteins and are termed “adipocytokines”. Adiponectin, resistin, visfatin, retinol binding protein-4 (RBP-4) and leptin are a few such proteins. Adiponectin is a multimeric protein, acting via its identified receptors, AdipoR1 and AdipoR2. It is a potential biomarker for metabolic syndrome and has several antiinflammatory actions. Adiponectin increases insulin sensitivity and ameliorates obesity. Resistin, another protein secreted by the adipose tissue, derived its name due to its involvement in the development of insulin resistance. It plays a role in the pathophysiology of several conditions because of its robust proinflammatory activity mediated through the activation of extracellular signal regulated kinases 1 and 2 (ERK 1/2). In 2007, resistin was reported to have protective effect in ischemia-reperfusion injury and myocyte-apoptosis in the setting of myocardial infarction (MI). RBP-4 is involved in the developmental pathology of type 2 diabetes mellitus and obesity. Visfatin has been described as an inflammatory cytokine. Increased expression of visfatin mRNA has been observed in inflammatory conditions like atherosclerosis and inflammatory bowel disease. Leptin mainly regulates the food intake and energy homeostasis. Leptin resistance has been associated with development of obesity and insulin resistance. Few drugs (thiazolidinediones, rimonabant, statins, etc.) and some lifestyle modifications have been found to improve the levels of adipocytokines. Their role in therapy has a lot in store to be explored upon.

Cardioprotective Effects of Lagenaria siceraria Fruit Juice on Isoproterenol-induced Myocardial Infarction in Wistar Rats: A Biochemical and Histoarchitecture Study

The present study was designed to evaluate the cardioprotective effects of Lagenaria siceraria fruit juice in isoproterenol-induced myocardial infarction. Rats injected with isoproterenol (200 mg/kg, s.c.) showed a significant increase in the levels of serum uric acid, tissue Na ++ and Ca ++ ions and membrane-bound Ca +2 -ATPase activity. A significant decrease in the levels of serum protein, tissue K + ion, vitamin E level, and the activities of Na + /K + -ATPase and mg +2 -ATPase was observed. Isoproterenol injected rats also showed a significant increase in the intensity of lactate dehydrogenase isoenzyme and histopathologic alterations in the heart. Treatment with L. siceraria fruit juice (400 mg/kg/day, p.o.) for 30 days and administration of isoproterenol on 29 th and 30 th days showed a protective effect on altered biochemical and histopathologic changes. These findings indicate the cardioprotective effect of L. siceraria fruit juice in isoproterenol-induced myocardial infarction in rats.

Effect of vitamin E alone and in combination with lycopene on biochemical and histopathological alterations in isoproterenol-induced myocardial infarction in rats.

Background: The present study has been designed to evaluate the combined cardioprotective effect of vitamin E and lycopene on biochemical and histopathological alteration in isoproterenol-induced myocardial infarction in rats. Materials and Methods: Adult male albino rats of Wistar strain were treated with isoproterenol (200 mg/kg, s.c.) for 2 days at an interval of 24 h to develop myocardial infarction. Vitamin E (100 mg/kg/day, p.o.) and lycopene (10 mg/kg/day, p.o.) were administered alone and in combination for 30 days. Change in body weight and organ weight were monitored. Levels of serum marker enzymes (AST, ALT, LDH and CK-MB), lipid peroxidation, endogenous antioxidants (GSH, GPX, GST, SOD and CAT), membrane bound enzymes (Na+/K+ ATPases, Mg2+ ATPases and Ca2+ ATPases) were evaluated. LDH isoenzyme separation was carried out using gel electrophoresis. Histopathology of heart tissue was performed. Results: Induction of rats with isoproterenol resulted in a significant elevation in organ weight, lipid peroxidation, serum marker enzymes (AST, ALT, CK-MB and LDH), and Ca 2+ ATPases, whereas it caused a significant (P < 0.001) decrease in body weight, activities of endogenous antioxidants (GSH, GPx, GST, SOD and CAT), Na+/K+ and Mg2+ ATPases. ISO treated rats showed high intensity band of LDH1-LDH2 isoenzymes. Treatment with the combination of Vitamin E and lycopene for 30 days significantly attenuated these changes as compared to the individual treatment and ISO treated groups. Histopathological observations were also in correlation with the biochemical parameters. Conclusion: These findings indicate the synergistic cardioprotective effects of vitamin E and lycopene during ISO-induced myocardial infarction in rats.

Protective Effects of Dioscorea alata L. in Aniline Exposure‑Induced Spleen Toxicity in Rats: A Biochemical Study

Introduction: Present study was designed to evaluate the protective effects of ethanolic extract of Dioscorea alata L. (DA) on hematological and biochemical changes in aniline-induced spleen toxicity in rats. Materials and Methods: Wistar rats of either sex (200-250g) were used in the study and each group contains six rats. Splenic toxicity was induced in rats by administration of aniline hydrochloride (AH; 100 ppm) in drinking water for a period of 30 days. Treatment groups received DA (50 and 100 mg/kg/day, po) along with AH. At the end of treatment period, various serum and tissue parameters were evaluated. Result: Rats administered with AH (100 ppm) in drinking water for 30 days showed a significant alteration in general parameters (organ weight, body weight, water intake, feed consumption, and fecal matter content), hematological parameters (red blood cell ( RBC), white blood cell (WBC), and hemoglobin content), and biochemical parameters (total iron content, lipid peroxidation, reduced glutathione (GSH), and nitric oxide (NO) content) of spleen. Treatment with DA (50 and 100 mg/kg/day, po) for 30 days along with AH showed significant recovery in aniline-induced splenic toxicity. Conclusion: The present result showed that involvement of oxidative and nitrosative stress in aniline-induced splenic toxicity and DA protects the rats from the toxicity, which might be due to its antioxidant property and the presence of different phytochemicals.

Effects of Lagenaria sicessaria fruit juice on lipid profile and glycoprotein contents in cardiotoxicity induced by isoproterenol in rats.

This study investigated antihyperlipidemic effects of Lagenaria siceraria fruit juice (LSFJ) in isoproterenol (ISO)induced cardiotoxicity in rats. Rats treated with ISO (200 mg/kg, s.c.) showed a significant increase in the levels of triglycerides, cholesterol, and free fatty acids, in both serum and heart tissue. An increase in the levels of phospholipids, low-density lipoprotein, and very low-density lipoprotein-cholesterol, and decrease in high-density lipoprotein-cholesterol in serum and phospholipid levels in the heart were observed. ISO intoxicated rats also showed a significant decrease in the activities of lecithin: cholesterol acyl transferase, whereas lipoprotein lipase was found to be increased. Administration of LSFJ (400 mg/kg, p.o.) for 30 consecutive days and challenged with ISO on day 29th and 30th significantly attenuated these alterations and restored the levels of serum and heart lipids along with lipid metabolizing enzymes. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the protective effect of LSFJ during ISO-induced cardiotoxicity in rats.

Ipilimumab: Melanoma and beyond

Sir, Recently, USFDA has approved ipilimumab, a fully human monoclonal antibody, under the trade name Yervoy for the treatment of metastatic melanoma. Metastatic melanoma is one of the most common type of cancers, standing fifth while considering the frequency of occurrence of cancers. It is a type of skin cancer that demographically affects individuals in the fourth or fifth decade of their life. Incidence of the disease increases with age, and older men have the highest propensity of suffering from this disease. Primary risk factor for the occurrence of metastatic melanoma is prolonged exposure to UV in the range of 280 to 320 nm. Pathophysiology involves abnormal growth and proliferation of melanocytes in areas exposed to UV radiation. Full thickness ablative procedures are the primary modalities of treatment in such conditions, followed by radiation therapy. However, for patients in an advanced stage of the disease, surgical excision is not curative and they require adjunctive chemotherapy and immunotherapy.[1] IL-2 has been approved by the USFDA for immunotherapy in patients with metastatic melanoma. IL-2 stimulates cytotoxic T-lymphocytes which ultimately cause tumor cell lysis. A response rate of about 16% is achieved with this modality of treatment. Another drug approved for the treatment of this condition is dacarbazine, achieving an overall response rate of up to 25%. However, both the alternatives have their own shortcomings (chronic side effects, need to monitor laboratory functions, relapsing disease).[1] To prevail over this condition, Bristol-Myers Squibb (BMS) has come up with ipilimumab which is a fully human monoclonal antibody (IgG1 isotype).

Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats

Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200–250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid (40 mg/kg/day, p.o.), and combination of protocatechuic acid (20 mg/kg/day, p.o.) and ascorbic acid (20 mg/kg/day, p.o.) followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated. Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content), tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content), and membrane bound phosphatase (ATPase) compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity. Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats.

Tesamorelin: A hope for ART-induced lipodystrophy

Journal of Pharmacy and Bioallied Sciences April-June 2011 Vol 3 Issue 2 319  including gases with acid and alkaline characteristics.[2] It has been proved that lyophilized blood products are highly hygroscopic and can absorb gases and evaporations of toxic chemical substances. Contemporary sorbents for filtrating gas masks are based on active carbon. Abilities for sorption for some gases depend considerably on the presence of trace metals like copper, silver and cobalt.

Dronedarone: A New Therapeutic Alternative for Cardiac Arrhythmias

As a new therapeutic agent for cardiac arrhythmias, dronedarone (Multaq ® ), a drug from Sanofi-Aventis, was approved by the FDA on July 2, 2009. [1] It is now available in the market in the form of tablets having 400 mg of the active ingredient. For patients requiring drug therapy or electroshock therapy to retain their normal rhythms, dronedarone is a useful option. However, treatment with dronedarone was associated with an increased likelihood in deaths due to heart failure. [2] Hence, the FDA did not approve dronedarone without a warning for causing deaths in patients with heart failure. [3] Figure 1 shows the structure, the International Union of Pure and Applied Chemists (IUPAC) name, and chemical class of dronedarone.