Protective effect of trapidil and l-arginine against renal and hepatic toxicity induced by cyclosporine in rats.
BACKGROUND
Cyclosporine A (CsA) leads to renal and liver injury, production of free radicals and nitric oxide (NO) deficiency. This study investigates the possible protective effects of trapidil and L-arginine against CsA-induced tissue injury.


OBJECTIVE
Forty adult male Wistar rats (180 +/- 20 g) were divided into five groups, eight animals in each. The first group served as control, second group served as CsA group, third group served as CsA + trapidil group, fourth group served as CsA + L-arginine group, and fifth group served as CsA + trapidil + L-arginine group. Kidney and liver functions, inflammatory mediators, cytokines, oxidant and antioxidant parameters as well as histopathological studies of renal and liver tissue were assessed in all groups.


RESULTS
CsA induced renal and hepatic dysfunction, which was confirmed by laboratory and histopathological examination. Administration of trapidil diminished the renal and liver injury and significantly attenuated the levels of serum creatinine, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and oxidative stress, while it significantly elevated the level of serum nitric oxide and the activity of antioxidative stress. L-Arginine gave the same trend as trapidil, but trapidil effect was more pronounced. Coadministration of trapidil + L-arginine significantly ameliorated the toxic effect of CsA, but did not differ significantly from the effect of trapidil alone.


CONCLUSIONS
Treatment with trapidil or L-arginine diminished the renal and hepatic CsA-induced toxicity. However, the effect of trapidil was more pronounced. Therefore, treatment with trapidil alone may be the most economic and effective as a potential therapeutic agent in CsA injury.
Salem
Neveen A
NA
Medical Division, National Research Centre, Cairo, Egypt.
Salem
Emad A
EA
Maarouf
Aref M
AM
Kamel
Mostafa
M
Elgalaly
Hazem
H
Radwan
Mohamed
M
El-Dayem
Walid A Abd
WA
Eladl
Mahmoud
M
D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016572:Cyclosporine / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014192:Trapidil / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D016572:Cyclosporine; D001120:Arginine; D014192:Trapidil