Inhibition of thromboxane (Tx) synthesis by free radical scavengers.
Treatment with thromboxane (Tx) synthase inhibitors or free radical scavengers has been shown to afford protection from renal ischemia. Since free radicals are closely associated with thromboxane (Tx) synthesis, this study examines the thesis that free radical scavengers inhibit formation of Tx. Anesthetized rats (n = 42) underwent right nephrectomy. By random choice, before 45 min of left renal pedicle clamping, rats received: 0.5 ml dextrose placebo IV (n = 6); the hydroxyl radical scavenger dimethyl-thiourea (DMTU), 500 mg/kg IV (n = 10); or the superoxide scavenger superoxide dismutase (SOD), 24,000 Sigma Units (SU)/kg IV (n = 12). This dose of SOD was repeated before release of the clamp. Treatment with DMTU and SOD decreased plasma TxB2 levels following 5 min of reperfusion from 2,480 pg/ml in dextrose treated controls to 1,155 pg/ml (p less than 0.01) and 1,419 pg/ml (p less than 0.03), respectively. At 24 hr, DMTU and SOD therapy decreased creatinine from 3.0 mg/dl in controls to 1.6 mg/dl (p less than 0.01) and 2.1 mg/dl (p less than 0.05), respectively. At 24 hr, DMTU but not SOD decreased left renal weight from 113 to 94% (p less than 0.0003) of the weight of the previously removed right kidney, and histologically prevented acute tubular necrosis (p less than 0.05). In nephrectomized but nonischemic sham control rats (n = 7) plasma TxB2 and 6-keto-PGF1 alpha concentrations were 757 pg/ml and 82 pg/ml, creatinine level 0.9 mg/dl and kidney weight 94% of the previously removed right kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D058186:Acute Kidney Injury / Q000517:prevention & control*; D000818:Animals; D011464:Epoprostenol / Q000097:blood; D006801:Humans; D007668:Kidney / Q000648:ultrastructure; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D012078:Renal Artery Obstruction / Q000150:complications; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C038983:1,3-dimethylthiourea; D011464:Epoprostenol; D013482:Superoxide Dismutase; D013930:Thromboxane-A Synthase; D013890:Thiourea