Purpose: To investigate the effect of diclofenac sodium salt and cyclosporin A (CsA) on human lens epithelial cell (HLEC) growth in culture.
Methods: Cultures of HLEC were obtained from anterior capsules from extracapsular cataract surgery. Third-passage cells were seeded in 96-well plates in 0.1 ml culture medium. Cytotoxicity was estimated by the tetrazolium test in confluent monolayers after 24 h exposure to a wide range of concentrations of diclofenac and CsA. The effect of subcytotoxic concentrations of diclofenac and CsA on HLEC proliferation in subconfluent cultures was evaluated after 24 and 72 h of exposure. To investigate the relationship between PGE2 synthesis and the inhibitory effect of these drugs, after 24 h of exposure to diclofenac and CsA the production of PGE2 was measured by radioimmunoassay. We also tested the effect of exogenous PGE2 addition to diclofenac 72-h-treated cultures.
Results: Diclofenac and CsA (at concentrations > or = 65 microM and > or = 2.5 microM, respectively) inhibited the proliferation of subconfluent cultures of HLEC in a dose-dependent fashion. Diclofenac inhibits PGE2 synthesis, while CsA at high doses stimulates PGE2 synthesis of cultured HLEC. Exogenous PGE2 addition reversed in part the inhibitory effect of diclofenac.
Conclusions: Diclofenac and CsA at appropriate doses are effective in inhibiting cultured HLEC proliferation. This could be of interest to prevent posterior capsule opacification. Further in vivo experimental studies seem worthwhile.
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http://dx.doi.org/10.1007/BF00941726 | DOI Listing |
Drug Deliv Transl Res
June 2023
Departments of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Sila Katamur, Changsari, Kamrup, Assam- 781101, India.
Cyclosporin A (CsA, 0.05% w/w)-loaded positively charged emulsions were prepared based on castor oil, chitosan, poloxamer 188, glycerin and double-distilled water. To augment the shelf/storage-stability of original emulsions, the solid-dry powder for reconstitution was made by spray drying technique.
View Article and Find Full Text PDFBiomed Pharmacother
May 2018
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Egypt. Electronic address:
We recently reported that exposure to cyclosporine (CSA) plus diclofenac causes hypertension and impairs left ventricular (LV) and cardiac autonomic functions in female rats. Here, we tested the hypothesis that these effects could be mitigated by facilitated heme oxygenase (HO) signaling. Experiments were performed in female rats to assess the effects of 10-day treatment with CSA (25 mg/kg/day)/diclofenac (1 mg/kg/day) regimen on cardiovascular functions in absence and presence of maneuvers that upregulate HO or its enzymatic products.
View Article and Find Full Text PDFToxicol Appl Pharmacol
November 2017
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Egypt. Electronic address:
The endothelium-derived hyperpolarizing factor (EDHF) serves as a back-up mechanism that compensates for reduced nitric oxide (NO)/prostanoids bioavailability. Here we investigated whether (i) under conditions of vascular endothelium dysfunction, the immunosuppressant drug cyclosporine (CSA) upregulates EDHF-dependent renal vasodilations through altering CYP4A/CYP2C signaling, and (ii) calcium channel blockers modulate the CSA/EDHF/CYP interaction. Rats were treated with CSA, verapamil, nifedipine, or their combinations for 7days.
View Article and Find Full Text PDFLife Sci
September 2017
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. Electronic address:
Aims: The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity (BRS). Here we asked if these effects of CSA are influenced by co-administration of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH-oxidase (NADPHox)/Rho-kinase (ROCK) pathway mediates this interaction.
Materials And Methods: Female rats were treated for 10days with CSA (25mg/kg/day), diclofenac (DIC, COX-1/COX-2 inhibitor, 1mg/kg/day), celecoxib (COX-2 inhibitor, 10mg/kg/day), or their combinations.
Eur J Pharmacol
July 2017
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. Electronic address:
Cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) are used together to manage arthritic disorders with an immune component. Previous reports showed contrasting effects for NSAIDs on CSA nephrotoxicity and acute elevations in blood pressure. Both effects were ameliorated or exaggerated after selective cyclooxygenase-2 (COX2) and nonselective COX inhibition, respectively.
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