Rengarajulu Puvanakrishnan

Protective role of curcumin against isoproterenol induced myocardial infarction in rats

The effect of curcumin on the biochemical changes induced by isoproterenol (ISO) administration in rats was examined. ISO (300 mg Kg−1 administered subcutaneously twice at an interval of 24 h) caused a decrease in body weight and an increase in heart weight, water content as well as in the levels of serum marker enzymes viz creatine kinase (CK), lactate dehydrogenase (LDH) and LDH1 isozyme. It also produced electrocardiographic changes such as increased heart rate, reduced R amplitude and ST elevation. Curcumin at a concentration of 200 mg.Kg−1 when administered orally, showed a decrease in serum enzyme levels and the electrocardiographic changes got restored towards normalcy. Myocardial infarction was accompanied by the disintegration of membrane polyunsaturated fatty acids expressed by increase of thiobarbituric acid reactive substance (TBARS), a measure of lipid peroxides and by the impairment of natural scavenging, characterized by the decrease in the levels of superoxide dismutase, catalase, glutathione peroxidase, ceruloplasmin, alpha tocopherol, reduced glutathione (GSH) and ascorbic acid. The oral pretreatment with curcumin two days before and during ISO administration decreased the effect of lipid peroxidation. It was shown to have a membrane stabilizing action by inhibiting the release of β-glucuronidase from nuclei, mitochondria, lysosome and microsome. Curcumin pre- and co-treatment decreased the severity of pathological changes and thus, could have a protective effect against the damage caused by myocardial infarction (MI).

Lipase production from Aspergillus niger by solid-state fermentation using gingelly oil cake

Cultural conditions for the production of lipase by Aspergillus niger strain MTCC 2594 by solid-state fermentation using gingelly oil cake were standardized. A lipase activity of 363·6 U/g of dry substrate was obtained at 72 h under optimum conditions. Addition of various nitrogen sources, carbohydrates and inducers to the substrate was found to be ineffective. The enzyme was optimally active at pH 7·0 and 37°C, and was found to be stable between pH 4·0–10·0 and 4–50°C. The enzyme also showed remarkable stability in the presence of detergents and it could be effectively used for the removal of triglyceride soils in laundry.

Experimental myocardial necrosis in rats: role of arjunolic acid on platelet aggregation, coagulation and antioxidant status.

Arjunolic acid, a new triterpene and a potent principle from the bark of Terminalia arjuna, has been shown to provide significant cardiac protection in isoproterenol induced myocardial necrosis in rats. To further explore the mechanism of action of arjunolic acid, antiplatelet activity, anticoagulant assays, electrocardiographic changes, serum marker enzymes, antioxidant status, lipid peroxide and myeloperoxidase (MPO) have been measured and the results are compared with a potent cardioprotective drug, acetyl salicylic acid (ASA). Administration of isoproterenol produces electrocardiographic changes such as decreased R amplitude and increased ST segment elevation and has resulted in an increase in serum marker enzyme levels as well as a decrease in enzymatic and nonenzymatic antioxidant levels. Arjunolic acid at an effective dosage of 15 mg/kg body weight (pre and post treatment),when administered intraperitoneally (i.p.), effects a decrease in serum enzyme levels and the electrocardiographic changes get restored towards normalcy. Arjunolic acid treatment is also shown to prevent the decrease in the levels of superoxide dismutase, catalase, glutathione peroxidase, ceruloplasmin, α-tocopherol, reduced glutathione (GSH), ascorbic acid, lipid peroxide, MPO and the cardioprotection is confirmed by the histopathological studies.This study shows that the cardioprotection of arjunolic acid pre and post treatment could possibly be due to the protective effect against the damage caused by myocardial necrosis.

Effect of curcumin on cetrain lysosomal hydrolases in isoproterenol-induced myocardial infarction in rats

The effect of curcumin on lysosomal hydrolases in serum and heart was studied by determining the activities of β-glucuronidase, β-N-acetylglucosaminidase, cathepsin B, cathepsin D, and acid phosphatase. Rats treated with isoproterenol (30 mg/100 g body weight) showed a significant increase in serum lysosomal hydrolase activities, which were found to decrease after curcumin treatment. Isoproterenol administration to rats resulted in decreased stability of the membranes, which was reflected by the lowered activity of cathepsin D in mitochondrial, lysosomal, and microsomal fractions. Curcumin treatment returned the activity levels almost to normal, showing that curcumin restored the normal function of the membrane. Histopathological studies of the infarcted rat heart also showed a decreased degree of necrosis after curcumin treatment.

Whole cell immobilization of Ralstonia pickettii for lipase production

Abstract Different matrices viz. agar, alginate and polyacrylamide were examined for the immobilization of whole cells of Ralstonia pickettii. The enzyme activity of whole cells immobilized in agar beads was very low. Alginate beads had the inherent disadvantage of dissolving in phosphate based media and even glutaraldehyde treatment did not have any significant effect. A Tris–HCl system was found to be the best for alginate based immobilization of whole cells from R. pickettii and 4% alginate beads gave an optimal lipase activity of 14 U/ml per min. When different concentrations of polyacrylamide were tried for immobilization of R. pickettii whole cells, 15% polyacrylamide blocks showed a retention activity of 66% (25 U/ml per min) when compared to that of the free cells (40 U/ml per min). Bis-acrylamide concentration of 0.15 g/10 ml of buffer was ideal and the optimum whole cell concentration for polyacrylamide immobilization was 2.0 g/l of saline. Optimal immobilized whole cell concentration (polyacrylamide blocks) for lipase production was 20% and polyacrylamide blocks were reused three times effectively for lipase production. Of the three matrices examined for the immobilization of whole cells from R. pickettii, polyacrylamide gave the best performance.

Lipase from Ralstonia pickettii as an additive in laundry detergent formulations

An ideal detergent enzyme should be stable at high pH and temperature, withstand oxidising and chelating agents, be effective at low concentrations and have a broad substrate specificity. Studies have been carried out to find the efficacy of removal of triglyceride soil in laundry by lipase from Ralstonia pickettii with or without detergents. Important parameters viz. lipase and detergent concentration, time and temperature have been studied. Under optimal conditions, lipase in the presence of detergent increased the removal of oil by 24–27% over treatment with detergent alone.

DEXAMETHASONE INDUCED ALTERATIONS IN ENZYMATIC AND NONENZYMATIC ANTIOXIDANT STATUS IN HEART AND KIDNEY OF RATS

This study was designed to investigate the alterations in thiobarbituric acid reactants (TBA-reactants) and enzymatic and nonenzymatic antioxidant levels induced by dexamethasone (Dex) in heart and kidney and to find out whether these alterations induced by Dex and its hypertensive effect had any role in the maintenance of hypertension in this model. Administration of dexamethasone induced severe loss of body weight, significant increase in heart and kidney weights and also marked electrocardiographic changes. The protein content in heart and kidney increased significantly during Dex administration and returned to near normalcy after withdrawal. Total activity of lactate dehydrogenase showed a significant increase in heart till day 8 of treatment, whereas in serum, it exhibited a significant decrease. The activity of CK in heart showed an increase till day 8 of treatment and approached normalcy thereafter. In serum, CK exhibited a decrease till day 8, remaining insignificant thereafter. CKMB in heart showed an insignificant increase initially, reaching normal levels on Dex withdrawal, whereas in serum, it showed a significant decrease throughout the experimental period. Mean arterial pressure (MAP) and heart rate increased significantly, while a significant elevation in the ST segment was noticed during administration as well as after withdrawal of dex. The TBA-reactants levels were found to increase in heart and kidney during days 12 and 16 of administration with Dex and even after withdrawal of Dex, the levels were insignificantly elevated. The level of glutathione in heart and kidney increased from day 4 onwards and reached normalcy during the later stages of treatment and after withdrawal of Dex. The total sulfhydryl groups exhibited a significant increase in both heart and kidney throughout the experiment. The antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione S-transferase exhibited a significant decrease in heart during Dex administration whereas, in kidney, they exhibited a significant increase during treatment and after withdrawal of Dex. Thus, Dex induced rise in mean arterial pressure, significant alterations in electrocardiographic parameters and also marked alterations in enzymatic and nonenzymatic antioxidant levels and in the TBA-reactants level in heart and kidney.

Comparative studies on the interplay of testosterone, estrogen and progesterone in collagen induced arthritis in rats.

Rheumatoid arthritis (RA) is a sexually dimorphic autoimmune disorder exhibiting a higher disease prevalence and severity among females. This study was carried out to understand the role of the major sex hormones viz., testosterone, estrogen and progesterone on the severity in arthritis. The interplay of the sex hormones was studied in a rat model of collagen induced arthritis (CIA). The parameters used for analyzing the disease severity included paw volume, radiology, histopathology of joint, markers for bone turnover, cytokine profile, levels of pain mediator (prostaglandin E(2)) and immune response to type II collagen. Arthritis induction to castrated and ovariectomised rats resulted in enhanced inflammation thereby indicating the importance of sex hormones. Treatment with physiological doses of dihydrotestosterone and estrogen attenuated the inflammation, with estrogen exhibiting higher potency. Progesterone was not shown to have any significance in disease modification; however, when progesterone was administered in combination with estrogen, the protective effects of estrogen were noticed to decrease.

Curcumin treatment modulates collagen metabolism in isoprot3erenol induced myoxardial necrosis in rats

This study was carried out to evaluate whether curcumin, a potent antioxidant, had any specific role in the synthesis and degradation of collagen in rat heart with mocardial necrosis, induced by isoproterenol.HCI (ISO). Myocardial necrosis was induced by administration of ISO (30 mg/100 g body weight subcutaneously twice at an interval of 24 h) and studies on collagen metabolism were carried out with curcumin (200 mg/kg) pre-and co-treatment with ISO. The incorporation of 14C-proline into collagen was studied as an index of collagen synthesis. The heart weight /body weight ratio,heart RNA/DNA ratio and protein were found to increase significantly in ISO administered animals. Curcumin pre- and co-treatment with ISO reversed these changes and attenuated the development of cardiac hypertrophy two weeks after the second dose of ISO. Increased fractional synthesis rate and enhanced degradation of newly synthesized collagen were observed in ISO administered animals. Curcumin pre- and co-treatment with ISO was noticed to decrease the degree of degradation of the existing collagen matrix and collagen synthesis, two weeks after the second dose of ISO. The observed effects could be due to free radical scavenging capacity and inhibition of lysosomal enzyme release by curcumin.

A novel peptide derivative exhibits anti inflammatory and antioxidant activity in adjuvant induced arthritis in rats.

A tetrapeptide derivative PEP1261 {Boc-Lys-(Boc)-Arg-Asp-Ser-(tBu)-OtBu}, corresponding to residues 39–42 of human lactoferrin, was tested for its antiinflammatory action in adjuvant induced arthritis in rats. Administration of heat killed Mycobacterium tuberculosis (500 μg/0.1 ml of paraffin oil) intradermally into the foot pad of right hind paw resulted in an increased paw volume and an increase in the levels of reactive oxygen species and β-glucuronidase as well as a decrease in the antioxidants levels. PEP1261, at an effective dose of 10 mg/kg body wt., exhibited a significant antiarthritic activity as evidenced by lowering of paw volume and inhibited the free radicals toxicity by increasing the antioxidants levels. This peptide derivative was also shown to have a membrane stabilizing action by significantly decreasing the total and free activity of β-glucuronidase and inhibiting the rate of release of the enzyme from lysosomal rich fraction. Histopathological studies confirmed the above results by showing a decrease in mononuclear cell infiltration, hypertrophy, hyperplasia and pannus formation after PEP1261 treatment in arthritic rats.