Long-term cyclosporine treatment in non-transplanted rats and metabolic risk factors of vascular diseases.
Cyclosporine (CsA) is an immunosuppressive agent frequently used in the clinic for prevention of allograft rejection and for the treatment of autoimmune diseases. Despite its desired action on the immune system, CsA treatment may present serious adverse effects, which are masked by the concomitant use of other drugs. The search for effective immunosuppression protocols which does not affect the quality of life of patients is driving research to investigate the CsA involvement in vascular diseases, frequent in patients under immunosuppression. Thus, 45 non-transplanted Wistar rats were treated for 8 weeks with vehicle or 5 or 15 mg/kg CsA (n=15/group) by gavage administration to evaluate the specific influence of cyclosporine on the levels of risk factors (metabolic and inflammatory) of vascular disease and its mechanism of action. Therefore, serum insulin levels, glucose tolerance test, serum lipids profile, total homocysteine and fibrinogen levels were assessed. The biochemical alterations reported here suggest the development of a framework straight to diabetes. Glucose homeostasis was affected as indicated by decreased insulin levels and altered glucose tolerance test in CsA 15 mg/kg group compared to other groups. Serum insulin and total homocysteine levels presented a significant negative correlation (R=- 0.76, P<0.0001). Fibrinogen and serum lipids profiles were significantly increased in CsA 15 mg/kg group compared to other groups and correlated positively with total homocysteine levels. Considering the well-established correlation among insulin resistance, lipid and total homocysteine levels, hypercoagulability and atherosclerosis, we can assume that this protocol of long-term CsA treatment in non-transplanted rats alter biochemical parameters related to cardiovascular and cerebrovascular risk, mainly in CsA 15 mg/kg group. Insulin and tHcy serum levels appear to be central in this process.
Böhmer
Ana Elisa
AE
Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Souza
Débora Guerini
DG
Hansel
Gisele
G
Brum
Liz M B P
LM
Portela
Luis Valmor
LV
Souza
Diogo Onofre
DO
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood; D005340:Fibrinogen / Q000032:analysis; D005951:Glucose Tolerance Test; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D014652:Vascular Diseases / Q000209:etiology* / Q000378:metabolism
D007166:Immunosuppressive Agents; D007328:Insulin; D020738:Leptin; D008055:Lipids; D006710:Homocysteine; D016572:Cyclosporine; D005340:Fibrinogen