Effect of doxorubicin on the intestinal membranes in rats—Influence of α-tocopherol administration

The effect of α-tocopherol on doxorubicin induced changes in intestinal brush border and basolateral membranes were studied in rats. Rats were treated with doxorubicin (2.5 mg/kg body wt.), intravenously, weekly for 8 weeks. α-Tocopherol (400 mg/kg body wt.) was given orally, daily for 2 months. Intestinal basolateral membrane bound ATPases and brush border membrane bound alkaline phosphatase activities were found to be decreased significantly in doxorubicin treated rats. The lipid peroxide level was found to be elevated with a significant depletion in membrane sulphydryl groups. In α-tocopherol coadministered animals, the enzyme activities were found to be restored with concomitant reduction in lipid peroxide levels and an increase in the membrane sulphydryl groups. The membrane cholesterol and phospholipid levels which were altered in doxorubicin treated animals were found to be maintained significantly. The results are discussed with reference to the effect of α-tocopherol on lipid peroxidation and membrane sulphydryl groups.     

An early decrease in interphotoreceptor retinoid-binding protein gene expression in Abyssinian cats homozygous for hereditary rod-cone degeneration

Levels of interphotoreceptor retinoid-binding protein (IRBP) protein and message in retinas of Abyssinian cats homozygous for progressive rod-cone degeneration were determined at early ages, well before the onset of clinical retinal degeneration. IRBP gene expression was assessed by immunochemical quantitation of IRBP protein, and by Northern blotting and slot-blotting of total RNA using a human IRBP cDNA probe. Morphology was assessed by electron microscopy and immunocytochemistry. Levels of both IRBP protein and message in affected Abyssinian cat retinas were significantly reduced below normal as early as 4 weeks of age at the earliest stage of retinal disorientation. Opsin mRNA was more abundant in affected Abyssininian cat retinas than in control retinas. This was at least 1 year before the onset of clinical symptoms. The reduction in IRBP gene expression to levels significantly below normal well before the onset of retinal degeneration in affected Abyssinian cat retinas indicates that this represents a primary defect or at least an early problem that could itself cause adverse effects.     

Effect of cisplatin and other biological response modifiers on the activity of lysozyme, plasminogen activator and 5' nucleotidase by murine macrophages in vitro

In vitro effect of cisplatin and other biological response modifiers has been studied. It is observed that in vitro treatment of macrophage monolayers with cisplatin, rIFN Y, LPS or MDP either alone or in combination showed significantly increased activity of lysozyme, plasminogen activator and decreased activity of 5' nucleotidase. Priming of macrophages with rIFN Y had a significant effect in enhancing the activity of lysozyme and plasminogen activator when subsequently treated with cisplatin, MDP or LPS.     

HIV-infected macrophages resist efficient NK cell-mediated killing while preserving inflammatory cytokine responses

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Calmodulin-dependents stimulation of the NADPH oxidase of human neutrophils

The NADPH oxidase of human neutrophils is highly sensitive to calcium concentration and is inhibited in intact cells and cell-free preparations by various phenothiazine drugs. Addition of calmodulin to preparations of NADPH oxidase stimulates enzymatic rates from 1.4–2.5-fold. Addition of calmodulin and calcium, but not calcium alone, to NADPH oxidase preparations which have been inactivated by EDTA results in the restoration of activity. No activation is observed when membrane preparations containing latent NADPH oxidase are exposed to calcium and calmodulin. These studies suggest a role for calmodulin in the control of NADPH oxidase but that calmodium alone is not sufficient for activation.     

Effect of alpha-tocopherol on doxorubicin-induced changes in rat liver and heart microsomes.

Rats were treated with doxorubicin (2.5 mg/kg body wt, iv) once a week for 8 weeks. Alpha-Tocopherol (400 mg/kg body wt/day) was co-administered orally for 2 months. Cytochrome-P450 (Cyt-P450) and Cytochrome-b5 (Cyt-b5) levels decreased significantly in doxorubicin treated rats. Significant decreases were observed in glucose-6-phosphatase, Cyt-P450 and Cyt-b5 reductase activities. In vitro lipid peroxidation study showed that alpha-tocopherol significantly minimises the lipid peroxide formation by doxorubicin. There was a significant change in microsomal cholesterol and phospholipid levels. Alpha-Tocopherol co-administration reduced the alterations in xenobiotic metabolising system and microsomal lipid levels. The results were discussed with reference to drug metabolising enzymes, lipid peroxidation and antioxidant nature of alpha-tocopherol.