Diuretic response to cyclophosphamide in rats bearing a matrix metalloproteinase-9-producing tumour

Abstract

Summary When cyclophosphamide (CY) (100-120 mg kg-') was administered intravenously (i.v.) to normal F-344 rats, oliguria occurred over the 5-day observation period. Conversely, in rats bearing matrix metalloproteinase-9 (MMP-9) producing 1 3762NF mammary adenocarcinoma (MTLn3 clone), polyuria occurred chiefly during the first 24 h after CY treatment. In parallel with urine volume, a decrease in the urinary excretion of Nacetyl-beta-D-glucosaminidase (NAG) was observed during the first 5 days after CY treatment in normal rats, but it increased in MTLn3-bearing rats. No elevation in blood urea nitrogen (BUN) or serum creatinine (Cr) values was observed for either group. Both urine volume and urinary excretion of NAG after CY treatment were lower in rats bearing the MTC clone (lower production of MMP-9) than for those bearing the MTLn3 clone. In the case of treatment with cisplatin (CDDP, 4-6 mg kg-'), urine volume, urinary NAG excretion and BUN and serum Cr values all increased in normal rats and were all found to be higher in MTLn3-bearing rats than in normal rats. The diuretic response to these drugs in tumour-bearing (TB) rats may be associated with MMP-9 produced by the tumour cells. This report suggests that the nephrotoxicity due to anti-cancer drugs may change when the drugs are used for the treatment of patients bearing a MMP-9-producing tumour.Keywords: cyclophosphamide; matrix metalloproteinase-9; nephrotoxicity; cisplatin

Activity of d,l‐α‐Tocopherol (Vitamin E) against Cardiotoxicity Induced by Doxorubicin and Doxorubicin with Cyclophosphamide in Mice

“…Therefore, for the exact definition of serum α‐HBDH origin (heart, kidney, or both), more experiments measuring the enzyme activity from cardiac and renal tissue are necessary. So far, the simultaneous decrease in α‐HBDH and creatine kinase serum activity in current study together with other data (Kang et al 1991; Mizushima et al 1998) suggest that LDH1 and LDH2 leakage were the most probably due to myocardial damage.…”

“…In that case, significantly lower α‐HBDH activity in animals treated with doxorubicin and cyclophosphamide compared to the group treated with doxorubicin alone needs additional explanation. Nephrotoxicity was not reported as one of the major side effects in cyclophosphamide therapy (Goldberg et al 1986; Braverman et al 1991; Dow et al 1993), but results by Mizushima et al (1998) show that cyclophosphamide caused oliguria in treated rats. It is well known that renal damage induced by nephrotoxic activity of various cytotoxic drugs could be prevented by stimulation of diuresis.…”

Progression of cyclophosphamide-induced acute renal metabolic damage in carnitine-depleted rat model

“…While both CP and IFO have severe urotoxic side-effects, only ifosfamide is thought to be nephrotoxic, causing tubular damage and resulting in Fanconi syndrome [4][5][6][7]. However, recent studies have demonstrated that CP has nephrotoxicity besides its urotoxicity, which both in turn limit its clinical utility [8][9][10][11][12]. Since nephrotoxicity of CP is less common compared with its urotoxicity, not much importance has been given to study of the pathogenesis of CP-induced nephrotoxicity.…”