PARP inhibitors accelerate N-methyl-N-nitrosourea-induced cataractogenesis in Sprague-Dawley rats

Background: There have been no previous studies of the effects of poly(ADP-ribose) polymerase (PARP) inhibitors on N-methyl-N-nitrosourea (MNU)-induced cataractogenesis in rats. Materials and Methods: A single intraperitoneal injection of 70 mg/kg MNU was administered to 15-day-old male and female Sprague-Dawley rats. In Experiment 1, rats were then subcutaneously injected with 1000 mg/kg nicotinamide, either once or 3 times at 1-week intervals. In Experiment 2, rats were subcutaneously injected once with 50 mg/kg 3-aminobenzamide. For comparison, the following age-matched controls were included: MNU-untreated nicotinamide-injected rats, MNU-untreated 3-aminobenzamide-injected rats, and MNU-untreated PARP-inhibitor-untreated rats. Rats were examined for lens opacity. At 28 days after MNU injection, 10 to 20 rats per group were sacrificed. In Experiment 1, at 3 days after MNU injection, 10 rats per group were sacrificed for apoptosis and cell proliferation detection. Results: MNU caused lens epithelial cell apoptosis in the germinative zone, as indicated by TUNEL staining. However, regardless of MNU treatment, lens epithelial cell proliferation was consistently seen in the germinative zone and sporadically seen in the central zone. At 28 days after MNU, mature cataracts were observed. Nicotinamide significantly accelerated lens opacity and cataractogenesis, as indicated by a cataract index. 3-Aminobenzamide significantly accelerated the development of lens opacity and tended to accelerate cataractogenesis. Conclusion: The PARP inhibitors nicotinamide and 3-aminobenzamide accelerated MNU-induced cataractogenesis.