Potential involvement of environmental triggers in protein aggregation with mercuric chloride as a model.

Heavy metal based toxicity has a direct relation with the perturbation of protein structure. We have investigated the progressive unfolding of ovalbumin, in the presence of increasing concentration mercury (0-6.25 µM) using different spectroscopic techniques. Formation of amorphous aggregate has been observed at the physiological pH. Initial addition of HgCl2 resulted in the association of monomers to oligomers that proceeded to non-fibrillar aggregates on further addition. The sigmoidal curve obtained from the Stern-Volmer plot clearly divided into three stage transition. A strong lag phase is observed indicating the time dependence for the association of competent monomers. The second stage was resolved into non-cooperative binding. These results match very well with the data from atomic force microscopy and the free energy change observed in the regions. Raman spectroscopic studies indicated toxic antiparallel ß-sheets structure. Time dependent atomic force microscopy study revealed the off-pathway nature of amorphous aggregates. At molten globular state, similar quenching behaviour is observed. The atomic force microscopy images clearly indicate at pH 2.2 the initiation of fibril formation occurs at lower concentration of HgCl2 itself. Our results revealed the conformation switch of ovalbumin upon the contact of an environmental toxin and its possible way of toxicity.

Mechanistic investigation of PPARγ-facilitated anti-asthmatic effects of Galangin (Norizalpinin): Insights from in silico and in vivo analyses.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a multifaceted ligand-activated transcription factor that regulates inflammatory responses in asthma pathophysiology. The present study corroborates PPARγ-mediated anti-asthmatic action of the flavonoid, galangin (norizalpinin). In silico molecular interactions reveal that galangin formed three H-bonds (Glu291, Leu340 and Ser342) and a π-sigma bond (Arg288) with PPARγ, contributing to the binding affinity and stability of the complex. In vivo studies explore the role of galangin as a propitious PPARγ agonist in mitigating airway inflammation, thereby excluding ligand-independent action of PPARγ. Accordingly, oral administration of galangin significantly ameliorated airway hyperresponsiveness, inflammation and goblet cell hyperplasia by the suppression of IL-4, 5, 13, 17, TNF-α, NO, ROS, EPO, IgE and increase of IFN-γ in ovalbumin-induced allergic asthma model. PPARγ expression (mRNA and protein) studies were performed to elucidate a possible mechanism by which galangin modulates. Furthermore, to eliminate PPARγ-independent effects of galangin, a specific PPARγ antagonist (GW9662) was administered, which dramatically reversed the effects of galangin on PPARγ up-regulation, confirming the pleiotropic role of galangin as a PPARγ agonist in asthma therapeutics. Taken together, our findings communicate that PPARγ plays as a master regulator in the anti-asthmatic action of galangin.

Subcutaneous vaccination using injectable biodegradable hydrogels for long-term immune response.

Prolonged vaccine release enables gradual immunostimulation, providing long-term immunity. Herein, Vitamin E-PEG-Vitamin E triblock 'ABA' hydrogel, which is formed through physical cross-linking of flower-shaped micelles and can reside in vivo for >17 weeks, was employed for delivery of cancer preventive vaccines to provide sustained anticancer immunity. Mice vaccinated with hydrogel formulations produced a significantly higher quantity of antibodies compared to solution formulations. OVA was used to study EG.7-OVA tumor rejection in vaccinated mice. Among all formulations, OVA-loaded hydrogel containing aluminum-based adjuvant had the best therapeutic outcome, and only 2/10 mice developed solid tumors with significantly smaller tumor size. Moreover, no adverse effect on liver and kidney was detected with the hydrogel formulation. In a lymphoma metastasis mouse model, vaccination with the OVA-loaded hydrogel and adjuvant resulted in increased survival (66.7%) compared to other formulations (12.5-50%) over 100 days. This hydrogel is a promising formulation for sustained delivery of vaccines.

Preventative tracheal administration of interleukin-27 attenuates allergic asthma by improving the lung Th1 microenvironment.

BACKGROUND: Interleukin-27 (IL-27) modulates CD4+ T-cell differentiation and function. The aim of this study is to investigate the effect and molecular mechanisms of IL-27 on the development of asthma. METHODS: IL-27 was intranasally administered in an ovalbumin-induced asthma model, and lung mononuclear cells and different Th cell classes were detected by fluorescence-activated cell sorting. The effect and mechanisms of IL-27 on human bronchial epithelial (HBE) cells were investigated by measuring changes in chemotactic factors, cytokines, transcription factors, and signaling pathways. RESULTS: We found that intranasal administration of IL-27 could attenuate airway inflammation and hyperresponsiveness, upregulate the type 1 T helper (Th1)-T memory (Tm) cells and regulatory T (Treg) cells subgroups of lung tissue lymphocytes, and diminish the levels of type 2 T helper (Th2) cytokines. IL-27 upregulated the expression of C-C motif chemokine ligand 2 (CCL2), CCL3, and CCL4 in HBE cells and promoted the production of chemotactic factors to attract monocyte recruitment. Recruited monocytes secondarily secreted IL-27 to influence HBE cells in a positive feedback cycle. After IL-27 intervention, signal transducer and activator of transcription 1 (STAT1) phosphorylation increased, while STAT4 and STAT6 phosphorylation declined. CONCLUSIONS: Preventative intranasal administration of IL-27 can recruit more IL-27-secreted monocytes to the airway and change the different T-cell classes in lung. The improved Th1 environment helps to alleviate Th2-mediated allergic asthma by repairing the STAT1 pathway but not the STAT4 pathway.

Anti-asthmatic activity of phenolic compounds from the roots of Gastrodia elata Bl.

We previously reported that 4-hydroxy-3-methoxybenzaldehyde has the most potent anti-inflammatory and analgesic activity of eight phenolic compounds obtained from the dried roots of Gastrodiaelata (GE) Blume (Orchidaceae); its activity may be related to inhibition of cyclooxygenase activities and oxidation. In the present study, the effects of nine phenolic compounds from GE on immediate-phase (IAR) and late-phase (LAR) asthmatic responses after aerosolized-ovalbumin (OA) challenge were evaluated by determining the specific airway resistance (sRaw) using a double-chambered plethysmograph in conscious guinea pigs with IgE-mediated asthma. Furthermore, recruitment of leukocytes, histamine release, and eosinophil peroxidase (EPO) and phospholipase A(2) (PLA(2)) activities were determined in bronchoalveolar lavage fluids (BALF) 24h after the antigen challenge. 4-Hydroxy-3-methoxybenzyl alcohol (12.5mg/kg) significantly (p<0.05) inhibited sRaw in IAR and in LAR by 51.97+/-4.96% and 39.93+/-3.46%, respectively, compared to that of the controls. Further, hydroxy-3-methoxybenzyl alcohol significantly (p<0.05) inhibited recruitment of leukocytes in accordance with amelioration of eosinophilia and neutrophilia, histamine (30.66+/-5.20%), EPO activity (21.58+/-2.02%), and specific PLA(2) activity (16.60+/-2.52%) in BALF compared with the control. In addition, bis-(4-hydroxyphenyl) methane, 4-hydroxy-3-methoxybenzoic acid, and 4-hydroxy-3-methoxybenzaldehyde (12.5mg/kg) significantly (p<0.05) inhibited sRaw, while bis-(4-hydroxyphenyl) methane, benzyl alcohol, and 4-hydroxybenzaldehyde at 12.5mg/kg significantly (p<0.05) inhibited leukocytes, histamine, EPO and PLA(2) activities in BALF compared with the controls. The phenolic glycoside, parishin had less activity compared to aglycones, 4-hydroxybenzyl compounds. These results suggest that the C(4) hydroxy and C(3) methoxy radicals in benzyl alcohols and aldehydes play important roles in mediating the anti-asthmatic activities of these compounds.

Influence of sodium chloride and glucose on acid-induced gelation of heat-denatured ovalbumin.

We examined the effects of NaCl and glucose on cold-set ovalbumin gelation. Cold-set gels were prepared by adding glucono-delta-lactone (GDL) to a 2% heated ovalbumin solution. For the gel prepared from ovalbumin heat-denatured with NaCl and glucose, the gel with 10 mM NaCl was most transparent and had high gel strength. Its maximum complex shear modulus (G*) and turbidity were 2.5 times greater and 3 times lower, respectively, than those of the gel without NaCl. The turbidity of the gel with the higher NaCl content increased steeply after the addition of GDL and did not change during the experimental period. The maximum G* of the gel exhibited positive correlations with the molar mass, radius, and surface hydrophobicity of soluble aggregates and the NaCl content, but the turbidity exhibited negative correlations with these factors. The presence of glucose did not significantly affect the turbidity or rheological properties of the gel. For the gel prepared by adding NaCl and glucose with GDL, the presence of glucose did not affect the turbidity, but the maximum G* decreased in inverse proportion to the glucose content. The turbidity of the gel with higher NaCl content (>or= 50 mM) was the greatest among all samples, and the increased turbidity was maintained throughout the measurements. The gels with 50 and 100 mM NaCl exhibited thixotropy during shearing at a constant shear rate. Therefore, the presence of NaCl and glucose during cold gelation could facilitate the preparation of cold-set gels having various properties for food applications.

Molecular differences between the divergent responses of ovalbumin-specific CD4 T cells to alum-precipitated ovalbumin compared to ovalbumin expressed by Salmonella.

CD4 T helper (Th) cell differentiation defined by in vitro cytokine-directed culture systems leaves major gaps in our knowledge of the mechanisms driving divergent Th differentiation. This is evident from our analysis of the response of mouse ovalbumin-specific CD4 T cells to different forms of ovalbumin that induce markedly distinct responses in vivo. We show that live attenuated ovalbumin-expressing Salmonella (SalOVA) induce Th1-associated T-bet and IFN-gamma. Conversely, alum-precipitated ovalbumin (alumOVA) induces the Th2-associated GATA-3 and IL-4. The early diversity occurring within these CD4 T cells isolated 3 days after immunization was assessed using real-time RT-PCR microfluidic cards designed with 384 selected genes. The technique was validated both at the population and single cell levels at different stages of the responses, showing beta2-microglobulin to be a more stably expressed reference mRNA than either beta-actin or 18S RNA. SalOVA was then shown selectively to induce the OVA-specific CD4 T cells to produce many chemokines and pro-inflammatory cytokines, contrasting with alumOVA-induced cells that only produced a few Th2-associated cytokines. Several cytokines and features associated with follicular helper functions were induced in the OVA-specific CD4 T cells by both antigens. Finally, IL-17RB is strongly associated with OVA-specific CD4 T cells responding to alumOVA, suggesting that alum may promote Th2 immune response through a role for the IL-25/IL-17RB pathway.

Conformational changes in proteins in vitro as a means of predicting the acute toxicities of chemicals.

Experimental data are presented on ovalbumin denaturation (OD, EC10) and human acetylcholine esterase (AChE) inhibition (IC50) in vitro, following exposure to the chemicals used in the international Multicentre Evaluation of In vitro Cytotoxicity (MEIC) programme. Data were obtained for 40 (OD test) and 43 (AChE test) of the 50 MEIC chemicals. These data were compared with similar data from other methods used in the MEIC programme, and good correlations (R2) were obtained with data from MEIC studies on cell lines: 0.80 for human, 0.81 for other animal, and 0.78 for fish cell line IC50 values and AChE values, and 0.76 for human, 0.69 other animal and 0.75 for fish cell line IC50 values and OD values. The correlation increased substantially, if chemicals which freely cross the blood-brain barrier were solely considered, with R2 = 0.90 for human, 0.90 for other animal, and 0.82 for fish cell line IC50 values and AchE values, and 0.87 for human, 0.86 for other animal, and 0.92 for fish cell line IC50 values and OD values, in this case. Such chemicals are the main cause of non-specific depression of the central nervous system (CNS). The AChE IC50 permits a good prediction of human acute toxicity, similar to the IC50 values obtained with human cell lines and the same MEIC chemicals. These results confirm the basal toxicity hypothesis formulated by Björn Ekwall. It is concluded that in vitro methods based on the disruption of the functions of the proteins vital for body operation can be used as an alternative to the cell culture methods, when non-specific toxic effects of chemicals on humans and animals are evaluated.

Binding properties of HABA-type azo derivatives to avidin and avidin-related protein 4.

The chicken genome encodes several biotin-binding proteins, including avidin and avidin-related protein 4 (AVR4). In addition to D-biotin, avidin binds an azo dye compound, 4-hydroxyazobenzene-2-carboxylic acid (HABA), but the HABA-binding properties of AVR4 are not yet known. Differential scanning calorimetry, UV/visible spectroscopy, and molecular modeling were used to analyze the binding of 15 azo molecules to avidin and AVR4. Significant differences are seen in azo compound preferences for the two proteins, emphasizing the importance of the loop between strands beta3 and beta4 for azo ligand recognition; information on these loops is provided by the high-resolution (1.5 A) X-ray structure for avidin reported here. These results may be valuable in designing improved tools for avidin-based life science and nanobiotechnology applications.

Nitration enhances the allergenic potential of proteins.

BACKGROUND: Recent investigations have shown that proteins, including Bet v 1a, are nitrated by exposure to polluted urban air. We have investigated immunogenic and allergenic properties of in vitro nitrated allergens in in vivo models. METHODS: Untreated and nitrated samples of ovalbumin or Bet v 1a were compared for their ability to stimulate proliferation and cytokine secretion in splenocytes from DO11.10 or from sensitized BALB/c mice, and for their ability to induce specific immunoglobulin (Ig)G1, IgG2a and IgE in sensitized mice. Additionally, sera from birch pollen-allergic individuals were analysed for IgE and IgG specific for nitrated Bet v 1a. RESULTS: Upon splenocyte stimulation with nitrated as compared with unmodified allergens, proliferation as well as interleukin 5 and interferon-gamma production were enhanced. Sera of mice sensitized with nitrated allergens showed elevated levels of specific IgE, IgG1 and IgG2a, compared with sera from mice sensitized with unmodified allergens. Moreover, cross-reactivity of antibodies against unrelated, nitrated allergens was observed in mice. We also found higher amounts of functional, specific IgE against nitrated than against untreated Bet v 1a in sera from birch pollen-allergic patients. CONCLUSIONS: Our findings suggest that nitration enhances allergic responses, which may contribute to an increased prevalence of allergic diseases in polluted urban environments.

[Forecasting parameters of acute chemical toxicity according to in vitro conformation changes of proteins].

The authors analyze experimental data on in vitro effects induced by chemicals that were used throughout MEIC toxicologic studies in ovalbumin and acetylcholinesterase of human RBC. Influence on proteins is compared to acute toxicity caused by the chemicals in humans and various cell lines. The conclusion is that the method is prospective for screening of acute chemical toxicity signs in humans.

Inhibitory activities of aromatic amino acid esters and peptides against ovalbumin permeation through Caco-2 cell monolayers.

Trp, Phe, and Tyr ethyl esters and their dipeptides with Gly at the C-terminals inhibited ovalbumin (OVA) permeation through Caco-2 monolayers. The inhibitory activity of Trp ethyl ester was the highest at near the concentration of 10(-6) M. It was suggested that Trp ethyl ester inhibited transcellular permeation of OVA.

Effects of fexofenadine on T-cell function in a murine model of allergen-induced airway inflammation and hyperresponsiveness.

There is renewed interest in antihistamines for the treatment of allergic asthma. A growing body of literature has shown that the newer compounds can affect inflammatory cell accumulation and cytokine/chemokine production. In a murine model of allergen-induced airway inflammation and hyperresponsiveness, the ability of fexofenadine to affect these outcomes was tested in a primary sensitization and challenge model and after treatment of donor mice before the adoptive transfer of T cells into recipients receiving limited allergen exposure. Mice were sensitized and challenged with allergen (ovalbumin). Airway function after inhaled methacholine was monitored in parallel to the assessment of tissue and airway inflammation and cytokine production. In further experiments, lung T lymphocytes from sensitized/challenged donor mice were transferred into naive recipients before limited airway challenge with the allergen. Administration of fexofenadine before challenge but after sensitization was effective in preventing tissue eosinophilia and airway hyperresponsiveness. Moreover, the treatment of donor mice with fexofenadine before transfer of lung T cells effectively prevented airway hyperresponsiveness and eosinophilia in naive mice exposed to limited airway challenge. These data therefore support the potential for fexofenadine in the treatment of allergen-induced airway hyperresponsiveness and inflammation.

Effect of lidocaine on ovalbumin and egg albumin foam stability.

Foam fractionation is a simple separation process that can remove and concentrate hydrophobic molecules such as proteins, surfactants, and organic wastes from an aqueous solution. Bovine serum albumin and ovalbumin have been widely used as model proteins due to their strong foaming potential and low price. Here, we study the effect of lidocaine on albumin foam, since drugs like lidocaine are known to bind with albumin. We observed that lidocaine not only enhances the amount of foam produced but also the stability of that foam as well. The foam stability was evaluated as the decay rate constant of the foam, determined from a change in height (or volume) of the foam over a given time period.

Fluticasone inhibits the progression of allergen-induced structural airway changes.

BACKGROUND: Inhaled corticosteroids are widely used as first-line therapy in patients with asthma. The concept of early introduction is more and more accepted. OBJECTIVE: In our rat model of airway remodelling, we investigated whether treatment with inhaled fluticasone propionate can inhibit further progression of established structural airway changes. METHODS: Sensitized Brown Norway rats were exposed to aerosolized ovalbumin (1%) from day 14 to 42. From day 28 to 42, animals were treated with inhaled fluticasone or placebo 30 min before each allergen challenge. One control group was exposed to PBS from day 28 to 42, a second control group throughout the whole experiment. RESULTS: Exposure to ovalbumin during 2 weeks induced structural airway changes, including epithelial cell proliferation, increase in airway wall area and fibronectin deposition. Goblet cell number was increased, although not significantly compared with PBS. Continuing allergen exposure for 2 weeks further enhanced each of these features. In addition, the amount of collagen in the airway wall was enhanced by 4 weeks allergen exposure compared with PBS-exposed animals. These additional increases were inhibited by treatment with fluticasone during the last 2 weeks. CONCLUSION: The progression of established allergen-induced structural airway changes in sensitized rats can be inhibited by treatment with fluticasone.

Long-term effects of feeding flaxseed-based diets. 1. Egg production parameters, components, and eggshell quality in two strains of laying hens.

We used a split-plot design of five diets: control (corn-soy) with 3.8% Ca, 10% flaxseed with 3.8% Ca, 10% flaxseed with 4.5% Ca, 10% flaxseed with 3.8% Ca and 22,000 IU vitamin D3/kg, and 10% flaxseed with 4.5% Ca and 22,000 IU vitamin D3/kg, and two strains of birds, DeKalb Delta (DD) and Hy-Line W-36 (HL), to evaluate long-term effects of flaxseed supplementation on egg production parameters. Each of the five treatments was randomly assigned and replicated six times with five hens per replicate pen from 21 to 57 wk of age. Phase I was from 21 to 39 wk, Phase II was from 40 to 48 wk, and Phase III was from 49 to 57 wk. Feed consumption was significantly (P < 0.04) greater for the hens fed 10% flaxseed diets (100.9 g) when compared to the corn-soy controls (99.3 g). Overall average egg production (P < 0.05) was 87.8, 87.1, 86.0, 87.1, 84.8, for diets 1, 2, 3, 4, and 5, respectively. Average hen weights during the study were significantly lower for the flaxseed-fed hens (1.559 kg) compared to the controls (1.616 kg). Egg weight was significantly affected by diet during Phase III with heavier eggs from flaxseed fed hens (62.6 g) compared to controls (61.44 g), but overall egg weight was not significantly affected. Average egg mass was not significantly affected by dietary treatments, but DD hens had a decrease in egg mass with Ca supplementation (Diet 2 vs. Diet 3), whereas HL egg mass increased with Ca supplementation. Percentage albumen had a significant strain effect and strain by diet interactions. Overall, significantly less albumen (P < 0.001) was produced by HL (59.4%) compared to DD (61.3%). Supplemental Ca increased albumen percentage in DD (interaction effect P < 0.03) and decreased albumen percentage in the HL strain. Flaxseed supplementation significantly increased albumen percentage (P < 0.02) when compared to the corn-soy control, 60.5 and 59.9%, respectively. An interaction effect (P < 0.01) was noted for percentage wet yolk, in which increasing Ca decreased wet yolk percentage in DD but increased yolk percentage in HL. Wet yolk percentage was also significantly (P < 0.001) less in DD (25.0%) when compared to HL (26.9%). Addition of flaxseed decreased yolk percent when compared to controls (P < 0.03) during Phase II. Ca supplementation significantly (P < 0.03) increased yolk solids in both strains. Grams of yolk solids per egg were affected by flaxseed supplementation (P < 0.06). Flaxseed eggs contained 7.18 g per egg yolk solids compared to 7.3 g in corn-soy control group. Wet shell percentage was significantly lower in the flaxseed diets (12.4%) when compared to the controls (12.6%). Addition of flaxseed to the diet of laying hens did not have any adverse effects on egg production parameters, but flaxseed supplementation can significantly alter weight of yolk solids and yolk and albumen percentages.

Assembly of MHC class I molecules with biosynthesized endoplasmic reticulum-targeted peptides is inefficient in insect cells and can be enhanced by protease inhibitors.

To study the requirements for assembly of MHC class I molecules with antigenic peptides in the endoplasmic reticulum (ER), we studied Ag processing in insect cells. Insects lack a class I recognition system, and their cells therefore provide a "blank slate" for identifying the proteins that have evolved to facilitate assembly of class I molecules in vertebrate cells. H-2Kb heavy chain, mouse beta 2-microglobulin, and an ER-targeted version of a peptide corresponding to Ova(257-264) were expressed in insect cells using recombinant vaccinia viruses. Cell surface expression of Kb-OVA(257-264) complexes was quantitated using a recently described complex-specific mAb (25-D1.16). Relative to TAP-deficient human cells, insect cells expressed comparable levels of native, peptide-receptive cell surface Kb molecules, but generated cell surface Kb-OVA(257-264) complexes at least 20-fold less efficiently from ER-targeted peptides. The inefficient assembly of Kb-OVA(257-264) complexes in the ER of insect cells cannot be attributed solely to a requirement for human tapasin, since first, human cells lacking tapasin expressed endogenously synthesized Kb-OVA(257-264) complexes at levels comparable to tapasin-expressing cells, and second, vaccinia virus-mediated expression of human tapasin in insect cells did not detectably enhance the expression of Kb-OVA(257-264) complexes. The assembly of Kb-OVA(257-264) complexes could be greatly enhanced in insect but not human cells by a nonproteasomal protease inhibitor. These findings indicate that insect cells lack one or more factors required for the efficient assembly of class I-peptide complexes in vertebrate cells and are consistent with the idea that the missing component acts to protect antigenic peptides or their immediate precursors from degradation.

Effect of trichloromethyl and trichloromethyl peroxyl free radicals on protein sulfhydryl content studies in model and in enzymatic carbon tetrachloride activation systems.

The effect of trichloromethyl and trichloromethyl peroxyl free radicals on protein sulfhydryl content was studied using both, model and enzymatic activation systems. In the model system activation of CCl4 to both free radicals was by UVC light and the target protein was either delipidated or undelipidated albumin. Under air, the CCl3O2. radicals were able to significantly decrease the protein SH in both albumin preparations. A small but signficant effect of UVC alone was observed with defatted albumin. No significant decreases in protein sulfhydryl were observed by .CCl3 attack on the defatted albumin. Reaction of CCl3O2. on cysteine SH led to chloroform formation indicating that a H abstraction reaction is involved in the process. UVC light has an own effect on SH group content. Similar results were obtained when the interaction was with undelipidated albumin rather than with cysteine. Their formation was significantly prevented by Trolox 1 mM in incubation mixture. When the CCl3O2. were generated by liver microsomal activation of CCl4 under air, a significant decrease in microsomal protein SH content was observed. NADPH also exerted an effect of its own. These decreasing effects were fully prevented by either Trolox or EDTA addition to incubation mixtures but not by alpha-tocopherol free or as a succinate ester. Incubation mixtures containing nuclear suspensions and NADPH led to a decrease in protein SH content. This decrease was not enhanced further by the presence of CCl4. No effect on the protein SH content was observed when either mitochondrial or cytosolic fractions were employed to attempt activation of CCl4 to .CCl3/CCl3O2. free radicals. The ability of CCl4 derived free radicals to decrease protein SH in liver microsomes could be involved in loss of activity of key SH enzymes of relevance such as microsomal calcium pump. This pump is known to be damaged during CCl4 poisoning. This effect was blamed to initiate alterations in calcium homeostasis later leading to CCl4 induced liver cell death.

Protective effects of carnosine against protein modification mediated by malondialdehyde and hypochlorite.

Malondialdehyde (MDA) and hypochlorite anions are deleterious products of oxygen free-radical metabolism. The effects of carnosine, a naturally occurring dipeptide (beta-alanyl-L-histidine), on protein modification mediated by MDA and hypochlorite have been studied. MDA and hypochlorite induced formation of carbonyl groups and high molecular weight and cross-linked forms of crystallin, ovalbumin and bovine serum albumin. The presence of carnosine effectively inhibited these modifications in a concentration-dependent manner. It is proposed that relatively non-toxic carnosine and related peptides might be explored as potential therapeutic agents for pathologies that involve protein modification mediated by MDA or hypochlorite.