L.M. Tripathi

Modulation of inflammatory mediators by ibuprofen and curcumin treatment during chronic inflammation in rat.

Inflammation is a protective tissue response occurring in three distinct phases, acute, subacute and a chronic proliferative phase. We undertook the present study to understand the overall immune response of the body during adjuvant induced chronic inflammation in rat and the effect of ibuprofen and curcumin on this response. Inflammatory mediators were estimated on day 21 and day 35 after adjuvant injection. The level of C-reactive protein increased to 200% on day 21 and then reduced to 50% on day 35 compared to control. Curcumin and ibuprofen further reduced the increased levels at both the time intervals. Haptoglobin level decreased to 42% on day 21 but increased to 5 times of control on day 35.Curcumin and ibuprofen reduced the increased levels at day 35. No significant change was observed in Prostaglandin-E2 and Leukotriene-B4 levels and in Lymphocyte proliferation. The level of Tumor Necrosis Factor-α increased by three folds on day 21, but came down to 88% on day 35. Ibuprofen treatment decreased the raised level on day 21 and increased the reduced level on day 35. Interleukin-1β increased to 2 folds on day 21 and 10 folds on day 35 which were significantly brought down by curcumin and ibuprofen. Nitric oxide level was reduced at both the time intervals, which were increased by drug treatment.

A novel pentasaccharide from immunostimulant oligosaccharide fraction of buffalo milk.

A processed oligosaccharide mixture of buffalo milk induced significant stimulation of antibody, delayed-type hypersensitivity response to sheep red blood cells in BALB/c mice. This also stimulated non-specific immune response of the animals measured in terms of macrophage migration index. A novel pentasaccharide has been isolated from the oligosaccharide containing fraction having immunostimulant activity of buffalo milk. This compound was isolated by a combination of gel filtration chromatography, silica gel column chromatography of derivatised oligosaccharides while the homogeneity was confirmed by high performance liquid chromatography. The results of structural analyses, i.e. proton nuclear magnetic resonance, fast atom bombardment mass spectrometry, chemical transformations and degradations are consistent with the following structure: GlcNAcbeta(1-->3)Galbeta(1-->4)GlcNAcbeta(1-->3)Gal beta(1-->4)Glc

STUDIES ON THE PROFILE OF IMMUNOSTIMULANT ACTIVITIES OF MODIFIED IRIDOID GLYCOSIDES

Immunostimulant activity profile of modified iridoid glycosides prepared from loganin (1), ketologanin (2) and arbortristoside A (3) have been studied and some structure–activity relationships have been obtained.

Permeability function related to cerebral microvessel enzymes during ageing in rats.

Cerebral microvessels from rats were prepared and characterized by their enrichment of specific markers, namely alkaline phosphatase (AP) and τ‐glutamyl transpeptidase (τ‐GT). Further, it was observed that AP and τ‐GT registered marked increase in aged rats. On the contrary, lactate dehydrogenase (LDH) activity decreased with the increasing age. Monoamine oxidase A activity in the microvessels decreased with age whereas MAO‐B moved in the reverse direction. No noticeable change was seen in acetylcholinesterase activity with increasing age of rats.

Effect of Plasmodium berghei infection and chloroquine on the hepatic drug metabolizing system of mice

The hepatic microsomal mixed-function oxidase (MFO) system was markedly impaired during Plasmodium berghei infection in mice. Cytochrome P-450 and other mono-oxygenases, viz. aniline hydroxylase, aminopyrine-N-demethylase and benzo(a)pyrene hydroxylase, were significantly decreased while microsomal heme showed a four-fold increase at peak parasitemia (greater than 50%). Oral treatment with chloroquine (16 mg kg-1 body wt for 4 days) of P. berghei-infected mice cleared the parasitemia within 72 h and almost normalized the altered levels of MFO indices, a week after cessation of treatment. The findings were further supported by the isoenzymic profile and drug-binding properties of terminal mono-oxygenase, cytochrome P-450.

Hepatic microsomal cytochrome P450 system during experimental hookworm infection

Experimental infection of golden hamsters with the hookworm, Ancylostoma ceylanicum, caused a profound decline in the hepatic microsomal cytochrome P450 content. Concomitant decrease was also noticed in aminopyrine N-demethylase and benzo[a]pyrene hydroxylase activities. However, aniline hydroxylase activity was only marginally elevated during the infection. Microsomal markers, viz., cytochrome b5, NADH-cytochrome-c reductase, and glucose-6-phosphatase, were not significantly altered. Hepatic tissue exhibited an accumulation of lipids, especially phospholipids, triglycerides, and cholesterol, resulting in fatty necrosis around the central vein region. Isolated hepatic microsomes showed a decrease in phosphatidylcholine content. Impairment in hepatic mixed function oxidase (MFO) activities was further confirmed by prolongation in hexobarbital sleeping time and zoxazolamine-induced paralysis. The hepatic MFO system of A. ceylanicum-infected hamsters responded qualitatively and quantitatively in a manner similar to that of control hamsters, upon stimulation with selective chemical inducers like phenobarbitone and 3-methylcholanthrene. Kinetic and in vitro substrate binding studies revealed that for aminopyrine the substrate affinity and the maximum enzyme activity (Vmax) were decreased, while for aniline the binding affinity was decreased and the binding capacity was enhanced. Results indicate specific/selective impairment of the hepatic microsomal cytochrome P450 system during hookworm infection and may have many practical implications in toxicology and pharmacology.

Immunomodulatory activity of hexapeptides related to proline rich peptide from colostrum.

Twelve analogues of an immunomodulatory hexapeptide YVPGFP (I) derived from Proline rich peptide (from colostrum) have been synthesized with modifications at positions 2, 4 and 6. In MLR assay one of the analogues exhibited approx 50% inhibition at 0.1 microg/mL concentration in contrast to prednisolone and I which caused around 70 and 20% suppression respectively, at the same concentration.

Biochemical and histopathological alterations in golden hamster during infection with Ancylostoma ceylanicum

Ancylostoma ceylanicum infection in golden hamsters (Mesocricetus auratus) caused marked biochemical and histopathological derangements. Jejunum, the primary site of infection, showed pronounced alterations compared with liver. Though the biochemical composition of jejunum was not significantly altered, activities of a few lysosomal enzymes were enhanced during hookworm infection. Marked damage to mitochondrial and microsomal membranes was reflected in changes in the activities of the marker enzymes from jejunal tissue. Lipid content, especially phospholipids and neutral lipids of hepatic tissue, exhibited marked elevation. Levels of hexokinase, phosphofructokinase, and lactate dehydrogenase were enhanced in jejunal as well as hepatic tissues, indicating activation of the glycolytic machinery during hookworm infection. A decrease in the levels of mucosal disaccharidases indicated damage to intestinal brush border membranes. However, alkaline phosphatase activity was increased in intestinal mucosa during the infection. Light microscopic examination of jejunal tissue revealed peeling off of the upper epithelial layer, activation of the goblet cells, and thickening of muscularis mucosa. However, hepatic tissue did not show gross alterations, except for slight necrosis in the centrilobular region.

Status of the microsomal mixed function oxidase system in the intestine, lungs and kidneys of hamsters during infection with Ancylostoma ceylanicum☆

Abstract Tekwani B. L., Tripathi L. M., Mukerjee S., Visen P. K. S., Katiyar J. C., Shukla O. P. and Ghatak S. 1988. Status of the microsomal mixed function oxidase system in the intestine, lungs and kidneys of hamsters during infection with Ancylostoma ceylanicum . International Journal for Parasitology 18 : 11–14. Infection of golden hamsters with Ancylostoma ceylanicum causes significant alterations in microsomal cytochrome P-450 and associated components in intestine, lungs and kidneys. In intestinal microsomes, cytochrome P-450, cytochrome b 5 , heme, cytochrome b 5 reductase, NADPH-cytochrome c reductase and benzo(a)pyrene hydroxylase decreased considerably. This generalized damage in jejunal microsomes appears to be due to marked pathological lesions in this tissue. Lung microsomes exhibited a decrease in cytochrome P-450, heme and benzo(a)pyrene hydroxylase, while cytochrome b 5 , and cytochrome b 5 reductase were not significantly affected. Renal microsomes showed elevation in cytochrome P-450 and benzo(a)pyrene hydroxylase, while other associated components remained unaffected.

Derivatives of human β-Casein fragments (54–59) exhibit highly potent immunosuppressant activity

Human beta-casein fragment (54-59) having the amino acid sequence Val-Glu-Pro-Ile-Pro-Tyr, has shown potent immunostimulant activity. Several analogs of this hexapeptide have been synthesized with modification at the N-terminal region and two analogs, viz. peptide I and peptide II have shown significant immunosuppressant activity in-vivo mouse model. Effect on cell mediated immunity (CMI) and humoral immunity was studied in mouse/SRBC model. Both the peptides failed to stimulate immune response in vivo and showed inhibition of CMI and humoral response to sheep red blood cells (SRBC). Peptides showed inhibition in alloantigen induced lymphocyte proliferation, i.e., mixed lymphocyte reaction (MLR) in vitro. Treatment with peptides inhibited the production of interferon-gamma (IFN-gamma), and increased the production of interleukin-4 (IL-4) as well as improved the skin graft survival. Cyclosporine a known immunosuppressant showed similar effect on mouse model. Present study thus provides a lead for the development of safe and effective immunosuppressant.