Synergistic effects of fish oil diet and dimethylthiourea in acute adriamycin nephrosis.
The synergistic effects of combining fish oil (FO) diet, which reduces thromboxane A production, with the free radical scavenger, dimethylthiourea (DMTU), were evaluated in acute adriamycin nephrosis, because proteinuria in adriamycin nephrosis is mediated by increased renal thromboxane A and free radical production. The effects of combined evening primrose oil (EPO) and DMTU were compared with the DMTU + FO combination because EPO increases prostaglandin E but not thromboxane A. After 7, 14, and 21 days, proteinuria was significantly (p < 0.05) reduced in rats receiving either DMTU + corn oil (CO) or DMTU + FO compared with untreated control rats. However, after 21 days, rats receiving DMTU + FO had significantly reduced urine protein excretion compared with those receiving DMTU + CO (103.9 +/- 20 mg daily vs 351.8 +/- 29.8 mg daily; P < 0.05). In contrast to FO, rats receiving EPO + DMTU had similar urine protein excretion to rats receiving DMTU + CO after 21 days (170.2 +/- 20.34 mg daily vs 179.45 +/- 26.38 mg daily). The mean serum cholesterol concentration was significantly (P < 0.01) reduced in rats receiving DMTU + FO (195.2 +/- 23.8 mg/dL) compared with DMTU + CO (377.9 +/- 28.5 mg/dL). Serum triglyceride levels also were significantly (P < 0.01) reduced in rats receiving DMTU + FO (52.5 +/- 26.4 mg/dL) compared with DMTU + CO (100.5 +/- 36.9 mg/dL). No significant differences in serum cholesterol concentrations or triglycerides occurred between rats receiving DMTU + CO and DMTU + EPO. Renal glutathione content was significantly (P < 0.05) increased by 23% in normal rats receiving FO diet and by 34% in rats receiving combined DMTU + FO compared with CO alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Milner
L S
LS
Department of Pediatrics, University of Nebraska Medical Center, Omaha.
Wei
S
S
Kazakoff
P
P
Watkins
L
L
Houser
M T
MT
D000818:Animals; D002784:Cholesterol / Q000097:blood; D003314:Corn Oil; D004041:Dietary Fats / Q000627:therapeutic use*; D004317:Doxorubicin / Q000633:toxicity*; D004359:Drug Therapy, Combination; D005228:Fatty Acids, Essential / Q000494:pharmacology; D005395:Fish Oils / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008041:Linoleic Acids; D009401:Nephrosis / Q000139:chemically induced / Q000628:therapy*; D031665:Oenothera biennis; D010938:Plant Oils; D011507:Proteinuria; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D017965:gamma-Linolenic Acid
D004041:Dietary Fats; D005228:Fatty Acids, Essential; D005395:Fish Oils; D000960:Hypolipidemic Agents; D008041:Linoleic Acids; D010938:Plant Oils; D014280:Triglycerides; C033266:Menhaden oil; C028498:evening primrose oil; D017965:gamma-Linolenic Acid; D003314:Corn Oil; D004317:Doxorubicin; C038983:1,3-dimethylthiourea; D002784:Cholesterol; D005978:Glutathione; D013890:Thiourea