Role of biometals in activation of immune cum inflammatory response in ovine ageing eye: a potential model for understanding human geriatric eye diseases.

The present study was designed to evaluate the age-related changes in biometal and antimicrobial peptide (cathelicidin) concentration and their role in oxidative cum pro-inflammatory cascade in an ovine animal model. Clinically healthy ovine (n = 126) were grouped as Group I (n = 55, age = up to 3 years), Group II (n = 52, age = above 3-below 6 years) and Group III (n = 19, age = 6 years above). Samples (aqueous humour and lens of the eye) were collected stored at - 80 °C till further analysis. In aqueous humour, the concentration of zinc (p < 0.001 in group III), copper (p < 0.05 in group II and p < 0.001 group III) and iron (p < 0.05 in group III) were significantly increased compared to group I. While as the concentration of magnesium were significantly decreased in group II (p < 0.001) and group III (p < 0.05) compared to group I. Similarly in eye lens the level of copper remained uniform as no significant change was observed across different age groups, while as significantly elevated levels of iron were observed in group III (p < 0.001) compared to group I. whereas, levels of lens Zinc (p < 0.05 in group II) and magnesium (p < 0.05 in group III and p < 0.001 in group II) were significantly decreased compared to group I. Age-dependent increase in levels of oxidation products which include advanced oxidation protein products (AOPP) in aqueous humour and lenses of group II and group III (p < 0.001) and MDA in aqueous humour of group III (p < 0.05) were found compared to levels recorded in group I. In contrast, levels of antioxidants which include lens vitamin C in group II and group III (p < 0.01) and lens superoxide dismutase (SOD) in group III (p < 0.001) were significantly increased compared to group I. Levels of pro-inflammatory cytokines in aqueous humour revealed significantly (p < 0.001) age-dependent increase in IL-1, IL-6 and TNF-α elevated in group III, and group II as compared to group I, However, cathelicidin level in aqueous humour of group III and group II were significantly (p < 0.001) lower as compared to groups I. Furthermore,the present study observed significant (p < 0.05) metal-metal positive interaction between copper levels in lens with levels of (iron and magnesium) in aqueous humour, levels of Zn in lens with levels of Zn in aqueous humour, levels of Mg in lens with levels of (Cu, Zn and Mg) in aqueous humour. In addition,the present study reports significantly negative interaction between levels of lens Fe with levels of lens magnesium level, aqueous humour magnesium level and levels of copper in aqueous humour. A significantly positive correlation was observed between oxidative markers and pro-inflammatory cytokine levels, while a significant negative correlation was observed between antioxidant defence markers and pro-inflammatory cytokine. These results suggest the essential role of age-related changes in biometal levels, oxidative stress and pro-inflammatory cytokines. These changes might help understand age-related changes in pathogenesis and effective targeting of pathogenetic pathways in ocular diseases.

Inhibition of peroxynitrite dependent tyrosine nitration by hydroxycinnamates: nitration or electron donation?

Peroxynitrite is a cytotoxic species generated by the reaction between superoxide and nitric oxide. In this study the ability of hydroxycinnamate antioxidants to decrease peroxynitrite-mediated nitration of tyrosine was investigated. The results obtained show that all compounds were able to inhibit nitration of tyrosine. The potency of inhibitory activity was in the order; caffeic acid > or = chlorogenic acid > or = ferulic acid > p-coumaric acid > ocoumaric acid > m-coumaric acid. Trolox, which was included in the study for comparative purposes, had an activity between that of ferulic acid and p-coumaric acid. The data obtained suggest that hydroxycinnamates can act by one of two possible mechanisms: preferential nitration for monophenolates and electron donation by catecholates.