Does gentamicin induce acute renal failure by increasing renal TXA2 synthesis in rats?
Acute renal failure (ARF) induced with large doses of Gentamicin (GM) (an aminoglycoside) was associated with increased urinary TXB (TXA) excretion which provoked a decrease of the ratios of urinary PGE2/TXB2 and 6-keto-PGF1 alpha (PGI2)/TXB2 excretions. Furthermore, as indicated by light microscopy most of the epithelial cells lining the proximal tubules show obvious lesions varying from swelling of their cytoplasm to complete necrosis. Either the inhibitor, OKY-O46, of TXA-synthetase, or volume expansion (VE) with isotonic saline (IS) of the experimental animals diminished urinary TXB excretion which provoked 1) augmentation of the ratios of urinary PGE/TXB and 6-keto-PGF1 alpha/TXB excretions, 2) elevation of creatinine clearance (Ccr) and 3) diminution of proteinuria (PU). This protection against ARF-by OKY-O46 and VE can a can be seen in microscopic sections where necrosis of proximal tubules is almost absent. Only a few proximal tubules show swelling of their epithelial cells and some focal areas of tubule necrosis. We suggest that the metabolites of arachidonic acid (AA), TXA2 a (potent vasoconstrictor agent) and prostaglandins (PGE2 and PGI2), (potent vasodilator factors), play an important role in the development (TXA2) or in the prevention (PGs) of ARF induced by this antibiotic.
Papanikolaou
N
N
Centre Franco-Hellenique de Diagnostic et de Recherche Biomedicale, Hopital General Agrinon, Grece/Hellas.
Peros
G
G
Morphake
P
P
Gkikas
G
G
Maraghianne
D
D
Tsipas
G
G
Kostopoulos
K
K
Arambatze
C
C
Gkika
E L
EL
Bariety
J
J
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008689:Methacrylates / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D002395:Catecholamines; D005839:Gentamicins; D008689:Methacrylates; D011453:Prostaglandins; D001127:Arginine Vasopressin; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; C034364:ozagrel