Effect of cyclosporin A on the expression of inducible nitric oxide synthase in the gingiva of rats.
BACKGROUND
The role of nitric oxide (NO) in the pathogenesis of cyclosporin A (CsA)-induced gingival overgrowth is still unknown. The purpose of this study was to evaluate the effect of CsA on the expression of nitric oxide synthases (NOS) in the gingival tissue of rats.


METHODS
Thirty male Sprague-Dawley rats were randomly assigned to a control and two test groups. Rats in each group received CsA (0, 10, or 30 mg/kg) daily by gastric feeding for 4 weeks. The plasma NO and the NOS enzyme activities were assayed at week 4 in the blood samples and in the gingiva and lung tissue specimens, respectively. The distribution of inducible nitric oxide synthase (iNOS) was further evaluated in tissues obtained from the gingiva and lung at the end of weeks 1 and 4 by immunohistochemistry.


RESULTS
In the CsA-treated animals, increased levels of plasma nitrites/nitrates were measured in comparison to those in control rats. Significantly greater iNOS enzyme activities were detected in lung and gingival tissues obtained from CsA-treated animals than from control animals. In addition, cells positively staining for iNOS were clearly observed in both gingival and lung tissues obtained from the CsA-treated animals by immunohistochemistry, whereas a few stained cells were found in those from the control group. The quantity of cells positively stained for iNOS was greater in tissue from week 4 than week 1.


CONCLUSIONS
The effect of CsA on gingival iNOS expression was evaluated in rats for 4 weeks. A greater iNOS expression in the gingiva was observed after CsA therapy by both enzyme activities and immunohistochemica staining. Therefore, we suggest that CsA can increase gingival iNOS expression, which may play an important role in cyclosporin-induced gingival overgrowth.
Gau
Ching-Hwa
CH
Department of Nursing, Kang-Ning Nursing College, Taipei, Taiwan.
Chou
Tz-Chong
TC
Chiu
Hsien-Chung
HC
Shen
E-Chin
EC
Nieh
Shin
S
Chiang
Cheng-Yang
CY
Fu
Earl
E
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology*; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000201:enzymology; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000097:blood; D009573:Nitrites / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D016572:Cyclosporine; D052247:Nitric Oxide Synthase Type II