Cyclosporin treatment alters prostanoid and thromboxane production by rat isolated kidney mitochondria.
This study was designed to investigate the effects of chronic treatment with cyclosporin A (CSA) on the endogenous synthesis of prostanoids (PGs) and thromboxane (Tx) by renal isolated medullary and cortical mitochondria. The administration of CSA, dissolved in 10% ethanol in olive oil, to male Wistar rats (20 mg kg-1 day-1 i.p.) for 14 days resulted in alterations in mitochondrial biosynthesis of immunoreactive PGs. The endogenous synthesis of thromboxane by medullary and cortical mitochondria isolated from CSA-treated rats was significantly enhanced by 120 and 55%, respectively, whereas the synthesis of prostaglandin E2 by medullary mitochondria was reduced by 35%. The synthesis of prostaglandin F2 alpha and prostacyclin was not affected by CSA treatment. The conversion of exogenous arachidonic acid to PGs and Tx by cortical mitochondria isolated from CSA-treated rats was significantly increased. In addition, CSA treatment resulted in i) a reduced acylation of arachidonic acid into medullary phospholipids by 25% and into medullary and cortical triglycerides by 33 and 27%, respectively, and ii) an increase in cortical and medullary triglycerides. We suggest that the alterations in the endogenous mitochondrial production of PGs and Tx caused by CSA, may play a role in the impairment of membrane mediated functions.
Erman
A
A
Institute of Nephrology and Hypertension, Beilinson Medical Center, Petah Tikva, Israel.
Chen-Gal
B
B
Rosenfeld
J
J
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D003524:Cyclosporins; D011453:Prostaglandins; D013931:Thromboxanes