title: Effects of topically applied tocotrienol on cataractogenesis and lens redox status in galactosemic rats.
abstract: OBJECTIVE
  Oxidative and nitrosative stress underlies cataractogenesis, and therefore, various antioxidants have been investigated for anticataract properties. Several vitamin E analogs have also been studied for anticataract effects due to their antioxidant properties; however, the anticataract properties of tocotrienols have not been investigated. In this study, we investigated the effects of topically applied tocotrienol on the onset and progression of cataract and lenticular oxidative and nitrosative stress in galactosemic rats.
  
  
  METHODS
  In the first part of this study, we investigated the effects of topically applied microemulsion formulation of tocotrienol (TTE) using six concentrations ranging from 0.01% to 0.2%. Eight groups of Sprague-Dawley rats (n = 9) received distilled water, vehicle, or one of the six TTE concentrations as pretreatment topically twice daily for 3 weeks while on a normal diet. After pretreatment, animals in groups 2-8 received a 25% galactose diet whereas group 1 continued on the normal diet for 4 weeks. During this 4-week period, topical treatment continued as for pretreatment. Weekly slit-lamp examination was conducted to assess cataract progression. At the end of the experimental period, the animals were euthanized, and the proteins and oxidative stress parameters were estimated in the lenses. In the second part of the study, we compared the anticataract efficacy of the TTE with the liposomal formulation of tocotrienol (TTL) using five groups of Sprague-Dawley rats (n = 15) that received distilled water, TTE, TTL, or corresponding vehicle. The mode of administration and dosing schedule were the same as in study 1. Weekly ophthalmic examination and lens protein and oxidative stress estimates were performed as in study 1. Lens nitrosative stress was also estimated.
  
  
  RESULTS
  During the 4-week treatment period, the groups treated with 0.03% and 0.02% tocotrienol showed slower progression of cataract compared to the vehicle-treated group (p<0.05), whereas the group treated with 0.2% tocotrienol showed faster progression of cataract compared to the vehicle-treated group (p<0.05). The lenticular protein content, malondialdehyde, superoxide dismutase, and catalase levels were normalized in the groups that received 0.03% and 0.02% tocotrienol. The lenticular reduced glutathione also showed a trend toward normalization in these groups. In contrast, the group treated with 0.2% tocotrienol showed increased lenticular oxidative stress. When the microemulsion and liposomal formulations were compared, the effects on cataract progression, lens oxidative and nitrosative stress, and lens protein content did not show significant differences.
  
  
  CONCLUSIONS
  Topically applied tocotrienol within the concentration range of less than 0.05% and more than 0.01% tends to delay the onset and progression of cataract in galactose-fed rats by reducing lenticular oxidative and nitrosative stress. However, topical tocotrienol at a concentration of 0.2% and higher aggravates cataractogenesis in galactose-fed rats by increasing lens oxidative stress. The anticataract efficacy of 0.03% microemulsion of tocotrienol did not differ from its liposomal formulations at the same concentration.
authors.affiliation: Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Nurul Alimah
authors.initials: NA
authors.lastname: Abdul Nasir
authors.affiliation: Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Renu
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Sushil
authors.initials: S
authors.lastname: Vasudevan
authors.affiliation: Faculty of Pharmacy, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Minaketan
authors.initials: M
authors.lastname: Tripathy
authors.affiliation: Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Renad
authors.initials: R
authors.lastname: Alyautdin
authors.affiliation: Faculty of Medicine, Brain and Neuroscience Communities of Research, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor, Malaysia.
authors.forename: Nafeeza Mohd
authors.initials: NM
authors.lastname: Ismail
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D002386:Cataract / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D018450:Disease Progression; D004655:Emulsions; D005136:Eye Proteins / Q000378:metabolism; D005693:Galactosemias / Q000150:complications* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008081:Liposomes / Q000737:chemistry; D008315:Malondialdehyde / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D055672:Static Electricity; D013312:Stress, Physiological / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D024508:Tocotrienols / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014783:Viscosity
chemical_list: D004655:Emulsions; D005136:Eye Proteins; D008081:Liposomes; D024508:Tocotrienols; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D002374:Catalase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D005978:Glutathione