Investigation of the therapeutic effectiveness of cereland in the experimental dry eye model created with benzalconium chloride in rat

MATERIALS AND METHODS: In our study, 46 healthy adult female Wistar Albino rats were used. The subjects were divided into six groups: Control, Dry Eye (DE), Loteprednol (L), 1/1 Greater Celandine Extract (K1/1), 1/10 Greater Celandine Extract (K1/10), and 1/100 Greater Celandine Extract (K1/100). Except for the control group, all other groups received topical administration of 0.2% BAK on the corneal surface twice daily for 14 days to induce an evaporative-type dry eye model. The control group received balanced salt solution for 28 days. The LOT group was treated with 0.5% Loteprednol Etabonate ophthalmic solution twice daily starting from day 15 until the end of the experiment. The K1/1 group received 1/1 Greater Celandine extract once weekly on days 14, 21, and 28; the K1/10 group received 1/10 extract, and the K1/100 group received 1/100 extract on the same schedule. Evaluation tests including phenol red thread, corneal fluorescein staining, and modified Cochet-Bonnet esthesiometry were performed once on days 0, 14, 21, and 28, by the same investigator and at the same time intervals. On day 29, the subjects were sacrificed. The excised corneal samples were used for histopathological and biochemical analyses. The data obtained were statistically analyzed, and a value of p<0.05 was considered statistically significant. FINDINGS: At the 4th week when the experiment was terminated, a statistically significant difference was found between the Disease Group (KG) and the Control group, and between the KG and K1/10 groups in terms of the phenol red cotton thread test (P<0.05). When corneal fluorescein staining scores were evaluated, a statistically significant difference was observed between the KG and all other groups (P<0.05). Regarding the modified Cochet-Bonnet esthesiometer results, a statistically significant difference was observed between the KG and all other groups (P<0.05). In the KG group, moderate stromal collagen degeneration and mild epithelial degeneration were observed. All treatment groups showed statistically significantly lower AQP-1 levels compared to the KG group. The AQP-1 levels in the K1/10 and K1/100 groups were also found to be statistically significantly lower than those in the Control group (P<0.05). All treatment groups showed statistically significantly lower AQP-5 levels compared to the KG group. The AQP-5 levels in the LOT and K1/100 groups were also found to be statistically significantly lower than those in the Control group (P<0.05). All treatment groups showed statistically significantly lower MMP-2 levels compared to the KG and Control groups (P<0.05). All treatment groups showed statistically significantly lower MMP-9 levels compared to the KG group (P<0.05). All treatment groups showed statistically significantly lower TIMP-2 levels compared to the KG group (P<0.05). All treatment groups showed statistically significantly lower NF-κB levels compared to the KG group (P<0.05). Among the treatment groups, the IFN-γ levels of the LOT, K1/10, and K1/100 groups were statistically significantly lower compared to the KG group (P<0.05). Among the treatment groups, only the TNF-α level of the K1/10 group was found to be statistically significantly lower compared to the KG group (P<0.05). All treatment groups showed statistically significantly lower IL-1β levels compared to the KG group (P<0.05). CONCLUSİON: As a result, it has been observed that Greater Celandine, whose therapeutic efficacy on Dry Eye Syndrome (DES) was investigated, demonstrated positive therapeutic effects at all three concentrations tested, as evidenced by clinical evaluation tests, biochemical findings, and histopathological analyses. The most favorable effect was observed with the 1/10 diluted concentration (K1/10). This was followed by the 1/100 diluted concentration in second place, and the undiluted pure concentration (1/1) in third place. Additionally, none of the three concentrations caused any side effects in the test subjects. Although Greater Celandine is popularly used in folk medicine for ophthalmic purposes, there is no study in the literature focusing on its use in this field. This study is the first to experimentally investigate the therapeutic effects of Greater Celandine in a DES model. From this perspective, it is believed that the results of our study will provide guidance and contribute to future research, academics working in this field, the scientific literature, and clinical practice. KEY WORDS: Dry Eye, Celandine, Benzalkonium Chloride, Rat