2nd International Electronic Conference on Synthetic Organic Chemistry (ECSOC-2), http://www.mdpi.org/ecsoc/, September 1-30, 1998
[dp005]

 

Protective role of tetramethyl luteolin in experimental cataracts.

Vit Patricia 1, Jacob Tim J C 2

1 Universidad de Los Andes, Dpto. Ciencia de los Alimentos, Facultad de Farmacia, Mérida, Venezuela. Fax +58-74-711802, e-mail vit@ula.ve

2 Eye Research Laboratory, Physiology Unit, School of Molecular and Mediacl Biosciences, University of Wales, Cardiff CF1 3US, UK. Fax +44-1222-874094, e-mail jacob@cf.ac.uk

Cataract is opacification of the ocular lens. Senile and diabetic cataracts are of epidemiological interest in human populations. More than 90% of blindness due to cataracts occur in developing countries (Who, 1991). This study follows an investigation on the putative anticataract properties of stingless bee (Hymenoptera; Apidae; Meliponinae) honeys in the tropical America. Eyedrops of honey from Melipona favosa favosa and Trigona (Tetragonisca) angustula angustula are used in Venezuela for this purpose (Vit Olivier, 1994). Luteolin is characteristic in the phenolic spectra of Venezuelan honeys (Vit et al., 1997) and luteolin derivatives are present in stingless bee honey (Vit et al., 1998). A 20 m g flavonoid/g honey has been reported (Ferreres et al., 1994). The anticataract activity of more active flavone substitutions has been related to the aldose reductase inhibition model for polyol cataracts (Varma and Kinoshita, 1976; Okuda et al., 1982; Shimizu et al., 1984). Methylation was a beneficial substitution to control cataracts (Chiou et al., 1992).

In a previous work, 20 flavonoids were screened in lenses under hypotonic stress to produce experimental cataracts monitored by digital image analyses, and a group of luteolin derivatives reduced lens opacification. In this work, two pulsed stresses of different nature were produced to apply tetramethyl luteolin 10-5 M treatment at different timing and target region. Ovine lenses were dissected from enucleated eyes by anterior approach and equilibrated in vials containing 5 ml of culture media at 37° C for 24 h prior to the experiment. They were cultured under hyperglycemic and hypocalcemic regimes. These regimes consisted in 24 h exposure to the modified culture medium, followed by 24 h exposure to control medium. The hyperglycemic regime produced complete opacification of the posterior lens and partial anterior, while the hypocalcemic regime produced a localized posterior cup opacification. The regionalized cataract was visible during the control medium phase in both regimes. Although the opacification patterns were different, suggesting mechanisms of diverse nature for each regime, tetramethyl luteolin 10-5 M was effective to prevent opacification only if applied during the control medium phase. These results are in agreement with the osmotic protection exerted by flavonoids as aldose reductase inhibitors and open a second avenue of a possible flavonoid action as anticataract agents at the calcium metabolism level. Protection against opacification was complete for the hypocalcemic model and was limited to the anterior lens in the hypoglycemic model. The elucidation of underlying mechanisms causing these visual effects could be approached by selective blocking and penetration studies complemented with histological descriptions.

The regionalization experiments are useful as preliminary screening aid to visualize the location of opacification and involved protective mechanisms, both in time and space. Interpretation of diagrams on discrete observations of the lens equatorial view, give insight on target zones that require further exploration. The clearly defined posterior band observed in the hypocalcemic regime might be related to the posterior subcapsular cataract. Therefore, this might be an adequate model to study the flavonoid effect in this type of cataract.

References

Chiou G. C. Y., Stolowich N. J., Zheng Y. Q., Shen Z. F., Zhu M., Min Z. D., 1992. Effects of some natural products on sugar cataract studied with nuclear magnetic resonance spectroscopy. J. Ocular Pharmacol. 8,115-120.

Ferreres F., Tomás-Barberán F. A., Soler C., García-Viguera C., Ortiz A., Tomás-Barberán F. A., 1994. A simple extractive technique for honey flavonoid HPLC analysis. Apidologie 25,21-30.

Okuda J., Miwa I., Inagaki K., Horie T., Nakayama M., 1982. Inhibition of aldose reductases from rat and bovine lenses by flavonoids. Biochem. Pharmacol. 31,3807-3822.

Shimizu M., Ito T., Terashima S., Hayashi T., Arisawa M., Morita N, Kurokawa S., Ito K., Hashimoto Y., 1984. Inhibition of lens aldose reductase by flavonoids. Phytochemistry 23,1885-1888.

Varma S. D., Kinoshita J. H., 1976. Inhibition of lens aldose reductase by flavonoids -their possible role in the prevention of diabetic cataracts. Biochem. Pharmacol. 25,2505-2513.

Vit P., Soler C., Tomás-Barberán F. A., 1997. Phenolic profiles of Apis mellifera and Melipona spp. honeys from Venezuela. Z. Lebensm. Unters. Forsch. 204,43-47.

Vit P., Tomás-Barberán F. A., 1998. Flavonoids in Meliponinae honey from Venezuela, related to their botanical, geographical and entomological origin to assess their putative anticataract properties. Z. Lebensm. Unters. Forsch. 206, 288-293.

Vit Olivier P., 1994. Las abejas criollas sin aguijón. Vida Apícola 63,34-42.

WHO Memoranda, 1991. Use of intraocular lenses in cataract surgery in developing countries. Bulletin WHO 69,657-666.


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