Safety and risk assessment of ceramide 3 in cosmetic products.

Ceramide 3 is used mainly as a moisturizer in various cosmetic products. Although several safety studies on formulations containing pseudo-ceramide or ceramide have been conducted at the preclinical and clinical levels for regulatory approval, no studies have evaluated the systemic toxicity of ceramide 3. To address this issue, we conducted a risk assessment and comprehensive toxicological review of ceramide and pseudo-ceramide. We assumed that ceramide 3 is present in various personal and cosmetic products at concentrations of 0.5-10%. Based on previously reported exposure data, the margin of safety (MOS) was calculated for product type, use pattern, and ceramide 3 concentration. Lipsticks with up to 10% ceramide 3 (MOS = 4111) are considered safe, while shampoos containing 0.5% ceramide 3 (MOS = 148) are known to be safe. Reported MOS values for body lotion applied to the hands (1% ceramide 3) and back (5% ceramide 3) were 103 and 168, respectively. We anticipate that face cream would be safe up to a ceramide 3 concentration of 3% (MOS = 149). Collectively, the MOS approach indicated no safety concerns for cosmetic products containing less than 1% ceramide 3.

Conjugation, characterization and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis.

Research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character in comparison to classical adjuvants. For example, polyacrylic acid (PAA) is a weak polyelectrolyte and has been used in several biomedical applications such as immunological studies, drug delivery, and enzyme immobilization. However, to our knowledge, there are no studies that document immune-stimulant properties of PAA in Leishmania infection. Therefore, we aimed to develop a potential vaccine candidate against leishmaniasis by covalently conjugating PAA with an immunologically vital molecule of lipophosphoglycan (LPG) found in Leishmania parasites. In the study, LPG and PAA were conjugated by a multi-step procedure, and final products were analyzed with GPC and MALDI-TOF MS techniques. In cytotoxicity experiments, LPG-PAA conjugates did not indicate toxic effects on L929 and J774 murine macrophage cells. We assume that LPG-PAA conjugate can be a potential vaccine candidate, and will be immunologically characterized in further studies to prove its potential.

Thirteen-week repeated dose toxicity of rice bran glycosphingolipid in Wistar Hannover (GALAS) rats.

Rice bran glycosphingolipid (RBGSL), one of the glycosphingolipids (GSLs), has been widely used as a food additive, a base of cosmetics, and so on. As a part of the safety assessment of RBGSL, a 13-week repeated dose toxicity study was performed in Wistar Hannover (GALAS) rats. Male and female rats were divided into 4 groups consisting of 8 animals and were given 0, 60, 250, and 1000 mg/kg BW of RBGSL orally 5 times weekly for 13 weeks. During the experiment, no deaths were observed in any groups, and there were no remarkable changes in general appearance, body weight, food and water consumption, hematological and serum biochemical parameters, organ weight and histopathological findings between the control and treated groups. On the basis of these data, the no-observed-adverse effect level (NOAEL) of RBGSL in Wistar Hannover rats was considered to be 1000 mg/kg BW/ day or more.

Inhibition of HIV-1-induced syncytia formation and infectivity by lipophosphoglycan from Leishmania.

In HIV-1 infection, the appearance of syncytia-inducing (SI) isolates is associated with a more rapid decline of CD4+ cells and progression to AIDS. Agents that inhibit either virus infection or syncytia formation have the potential to be therapeutically useful. Lipophosphoglycan (LPG), the major glycoconjugate of Leishmania, was recently shown to be a potent nonspecific inhibitor of viral membrane fusion. In this study, LPG demonstrated a dose-dependent inhibition of HIV-1-induced syncytia formation in CD4+ MT-2 cells infected with distinct SI isolates. Fragments of LPG were used to show that inhibition of syncytia formation was dependent on the length of the LPG fragment. Treatment of CD4+ cells or HIV-1 isolates with LPG inhibited infection in vitro. Furthermore, LPG inhibited the replication of SI viral isolates in CD4+ T cells in vitro. LPG had no toxic effects on peripheral blood mononuclear cells at the highest concentrations used in these assays. Further, LPG rapidly associated with the surface membrane of a human T cell line and subsequently disassociated over a 24-h period. The development of compounds capable of inhibiting HIV-induced syncytia formation should provide novel therapeutic approaches to control the spread of virus and disease progression.

Parasite escape mechanisms: the role of Leishmania lipophosphoglycan on the human phagocyte functions. A review.

Protozoan parasites of the Leishmania genus are the causative agents of important diseases in humans and animals. During their life cycle in vertebrate hosts, protozoa are able to live and proliferate within phagolysosomes of host phagocytic cells. The capacity to live in this hostile environment is likely due to the cell surface glycoconjugate expression. In particular, lipophosphoglycan (LPG), a major surface glycoconjugate of Leishmania promastigotes, has been reported to play an active role in protecting parasites within phagolysosomes via the impairment of killing mechanisms. In this review, the authors emphasize some novel LPG-mediated escape mechanisms of promastigotes from human phagocyte responses, such as the impairment of oxidative burst and of chemotactic activity. In the light of these findings, the knowledge of biological actions of LPG may be useful in order to prepare a vaccine against human leishmaniasis, using LPG defective avirulent mutant strains.