Ameliorated effect of L-arginine supplementation on gingival morphology in cyclosporin-treated rats.
BACKGROUND
The role of nitric oxide (NO) in the pathogenesis of cyclosporin (CsA)-induced gingival overgrowth is unknown. The purpose of the present study was to evaluate the effect of NO substrate (L-arginine) and blockade (N-nitro-L-arginine methylester-hydrochloride, L-NAME) on the gingival morphology in CsA-fed rats.


METHODS
Sixty CsA-fed (10 mg/kg/day) male Sprague-Dawley rats were assigned to 3 groups. Animals in 2 experimental groups received L-arginine (1% weight/weight) in rat chowder or L-NAME (50 mg/l) in drinking water, respectively, for 4 weeks. Rats in the control group were fed a normal diet and water. At week 0, 2, and 4, dental stone models were made from the mandibular anterior region and the gingival dimensions (width, depth, and height) were measured. The tail cuff blood pressure and the plasma nitrate level were also measured at week 4 to monitor the effects of L-arginine and L-NAME treatment.


RESULTS
No significant difference in the gingival dimensions was noticed at week 0; however, significant differences were observed at weeks 2 and 4, except the buccolingual depth at week 2. While the magnitude of gingival dimensions was large, moderate, and small in control, L-NAME, and L-arginine groups, respectively, we found significantly reduced gingival dimensions in both L-arginine supplement and L-NAME groups. Nevertheless, the reduced gingival overgrowth in the L-NAME treatment group was far less than that in the exogenous NO treatment group. Plasma NO2-/NO3- concentrations were also significantly different; i.e., from the highest to the lowest levels were the L-arginine, CsA control, and L-NAME group, respectively. A significantly increased mean and diastolic blood pressure was found in the L-NAME group compared to the L-arginine group.


CONCLUSIONS
Gingival morphology in CsA-fed rats was evaluated after NO substrate (L-arginine) and blockade (L-NAME) treatment for 4 weeks. Significantly decreased dimensions were noted in the L-arginine group compared to the CsA group at weeks 2 and 4. Although an inhibitory effect on the gingival morphology was also observed in the L-NAME group, another unknown mechanism might be involved. Within the limitations of the study, we suggest that NO may have an important role in the mechanism of CsA-induced gingival overgrowth.
Fu
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Department of Periodontology, School of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. dentalab@tpts5.seed.net.tw
Tz-Chong
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Liu
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Chiu
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D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005881:Gingiva / Q000187:drug effects; D019214:Gingival Overgrowth / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D016572:Cyclosporine; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester