Glucocorticoid amelioration of nephrotoxicity: a study of cephaloridine-methylprednisolone interaction in the rat.
Groups of ten male rats were treated with a high challenge dose of cephaloridine (CPH, 3750 mg kg-1), with methylprednisolone (MP, 100 mg kg-1) or with cephaloridine and methylprednisolone (CPH + MP) by single subcutaneous injection. A control group received the injection vehicles only. Urine was collected from all animals daily over 18-h collection periods, up to 96 h after treatment. Blood was collected at 24, 48, 72 and 96 h after treatment. At necropsy, kidneys were weighed, processed and examined histopathologically. Results show that methylprednisolone significantly ameliorated the nephrotoxicity of the challenge dose of cephaloridine. CPH-only treated rats had severe toxic nephrosis characterised by acute tubular necrosis, and elevated blood urea and creatinine. By contrast, the majority of CPH + MP treated rats had only a slight or moderate toxic nephrosis, and had lower blood urea and creatinine levels compared with rats treated with CPH only, indicating preservation of kidney function. Interestingly, rats treated with CPH + MP had higher urinary enzymes (alkaline phosphatase, lactate dehydrogenase, gamma glutamyltransferase and N-acetyl-beta-glucosaminidase) as well as protein and glucose, compared with rats treated with CPH only. This is taken to indicate that rats treated with CPH only had such marked kidney damage and necrosis that the population of cells able to produce these marker enzymes was significantly and rapidly depleted, but the protection afforded by methylprednisolone allowed CPH + MP treated rats to sustain urinary enzyme output. Effects on urinary glucose and other parameters such as body weight and kidney weight demonstrate interactions between glucocorticoid pharmacology and cephaloridine nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Harvey
P W
PW
AgrEvo UK Limited, Toxicology, Essex, UK.
Healing
G
G
Major
I R
IR
McFarlane
M
M
Purdy
K A
KA
Olatunde
O
O
Garcia Conesa
M T
MT
Everett
D J
DJ
Cockburn
A
A
D000818:Animals; D002509:Cephaloridine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004338:Drug Combinations; D004347:Drug Interactions; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004338:Drug Combinations; D002509:Cephaloridine; D008775:Methylprednisolone