Filingeri V, Giacomelli R, Famularo G, Rosati R, Nardi S, Calogero A, Iacona A, Stortoni F, Cramarossa L, Sacchetti S
Surgical Clinic, University of Rome Tor Vergata, Italy.
Drugs Exp Clin Res. 1989;15(4):159-64.
H2-receptor antagonists, such as cimetidine (C), ranitidine (R) and famotidine (F) seem to be effective in the prevention and treatment of stress ulcer in transplant recipients receiving cyclosporin A (CyA). The aim of this study was to detect the possible synergistic nephro- and hepato-toxicity of these drugs, assaying the serum creatinine (SC), ALT, AST levels, and the histological features of 45 young male Sprague-Dawley rats, divided into nine groups of five rats each. After 10 days of treatment the results showed: (i) serum CyA levels were increased in the group receiving daily CyA (5 mg/kg) + R(5 mg/kg) (2430 +/- 403 ng/ml; p less than 0.05 vs. controls) and in the group receiving daily CyA (5 mg/kg) +/- C (10 mg/kg) (2440 +/- 265 ng/ml; p less than 0.01 vs. controls); (ii) ALT and AST levels were increased in this latter group (ALT 223 +/- 133 UL, AST 114.67 +/- 39 UL; p less than 0.01 vs. controls); (iii) SC levels were normal; and (iv) steatosis of the liver was observed in these two groups. These findings suggest that C and R, but not F, may inhibit the hepatic cytochromes P-450 which are involved in the oxidative metabolism of the drugs. Furthermore, the high serum CyA levels seem to play a major role in the appearance of biochemical and histological damage to the liver.
H2受体拮抗剂，如西咪替丁（C）、雷尼替丁（R）和法莫替丁（F），似乎对接受环孢素A（CyA）的移植受者应激性溃疡的预防和治疗有效。本研究的目的是检测这些药物可能的协同肾毒性和肝毒性，检测45只年轻雄性Sprague-Dawley大鼠的血清肌酐（SC）、ALT、AST水平以及组织学特征，将其分为9组，每组5只大鼠。治疗10天后结果显示：（i）每日接受CyA（5mg/kg）+R（5mg/kg）的组（2430±403ng/ml；与对照组相比p<0.05）和每日接受CyA（5mg/kg）+/-C（10mg/kg）的组（2440±265ng/ml；与对照组相比p<0.01）血清CyA水平升高；（ii）后一组的ALT和AST水平升高（ALT 223±133UL，AST 114.67±39UL；与对照组相比p<0.01）；（iii）SC水平正常；（iv）在这两组中观察到肝脏脂肪变性。这些发现表明，C和R而非F可能抑制参与药物氧化代谢的肝细胞色素P-450。此外，高血清CyA水平似乎在肝脏生化和组织学损伤的出现中起主要作用。
