Physiology

Kaplan, Harriett; Brewer, Nathan; Blair, William H.

doi:10.1016/b978-0-12-262503-9.50018-9

Cited by 24 publications

(15 citation statements)

References 482 publications

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“…If the values observed for the GFR in control mice of this strain in each of the various studies discussed in this paper are compared, they are also similar (23.0 ± 1.9 ml min' i kg-', mean ± s.d., n = 25), providing further confirmation of reproducibility. This mean value is identical to that quoted for mannitol clearance, and hence GFR, in a review of mouse physiology (Kaplan et al, 1983).…”

Section: Discussionsupporting

confidence: 60%

The renal effects of N10-propargyl-5,8-dideazafolic acid (CB3717) and a non-nephrotoxic analogue ICI D1694, in mice

Jodrell

Newell²,

Morgan³

et al. 1991

Br J Cancer

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Summary N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino]-2-thenoyl)-L-glutamic acid (ICI D1694) is an analogue of the thymidylate synthase inhibitor, N'°-propargyl-5,8-dideazafolic acid (CB3717). CB3717 was found to be active in early clinical studies, but its use was limited by nephrotoxicity. ICI D1694 is a more potent antitumour agent than CB3717 and is also more water soluble. Previous studies have shown ICI D1694 to be non-toxic to the kidney following a single administration but its renal effects after chronic administration are unknown. To assess these effects, and further define the time course and dose relationship of CB3717-induced renal damage, an assay of glomerular filtration rate (GFR) has been developed which can be used in mice and hence in the screening of novel compounds. The '4C-inulin clearance assay developed was used to show a linear relationship between CB3717 dosage and renal damage (r=-0.989) following a single bolus dose (50-200mgkg-'), in mice. CB3717-induced renal damage is persistent (>6 weeks) and renal scarring was noted. ICI D1694 has been shown to be non-nephrotoxic following weekly administration of 250 mg kg-' for 6 weeks. Measurement of GFR has been shown to be a more sensitive indicator of impaired renal function than plasma urea and creatinine concentration, and the measurement of plasma creatinine concentration in particular, appears to be without value in the screening of potential nephrotoxins in certain mouse strains.Nl'-propargyl-5,8-dideazafolic acid (CB3717, Figure l.i.) is a folate based inhibitor of the enzyme thymidylate synthase (TS), which was found to be an active antitumour agent in early clinical trials in patients with breast, ovarian and hepatocellular carcinoma (Calvert et al., 1986;Cantwell et al., 1988; Bassendine et al., 1987). However, the clinical use of CB3717 was limited by its nephrotoxicity, which was observed in Phase I studies of both weekly (Vest et al., 1988) and 3-weekly administration schedules (Calvert et al., 1986;Sessa et al., 1988). Renal toxicity manifested primarily as a reduction in glomerular filtration rate (GFR). However, tubular damage was also identified by the measurement of the urinary enzymes, N-acetyl glucosaminidase (NAG) and leucine aminopeptidase (LAP). A >20% reduction in GFR was observed in seven of 12 (58%) patients receiving more than 400 mg m2 CB3717. In addition, urinary NAG and LAP levels were elevated in 50% of patients studied, although this elevation was not dose related (Calvert et al., 1986). CB3717-induced nephrotoxicity was thought to be due to the compound's relative insolubility at acid pH. However, despite adequate alkalinisation (pH ,8) of the urine, reductions in GFR (measured using creatinine clearance) of >20%, were still seen in 6/17 (35%) courses in patients treated at 400 mg m2 (Sessa et al., 1988). To circumvent toxicity related to drug precipitation in the kidney, a series of more soluble analogues of CB3717 have been synthesised. In addition to being devoid of renal toxic...

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Section: Discussionsupporting

confidence: 60%

The renal effects of N10-propargyl-5,8-dideazafolic acid (CB3717) and a non-nephrotoxic analogue ICI D1694, in mice

Jodrell

Newell²,

Morgan³

et al. 1991

Br J Cancer

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“…NE binding to adrenergic receptors on brown fat cells causes increased expression of uncoupling protein 1 (UCP-1) in the mitochondria such that most of the energy produced by oxidative respiration immediately generates heat rather than ATP. Indeed, it was shown long ago that heat production through this form of thermogenesis in mice can be triple that of basal metabolism, and is greater than any other animal investigated [14,15]. Living with chronic cold stress and the need for increased metabolic production of heat has considerable physiologic consequences because for each 1 8C drop in ambient temperature it takes about 46.3 kcal/m 2 /24 h to maintain normal body temperature [13].…”

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confidence: 99%

“…and states that mice should be housed between 20-26 8C. While a mildly cool room temperature helps to maintain the thermal comfort of animal care workers, it is also thought to be beneficial for mouse husbandry because it results in increased litter size and viability [15]. However, it was recently published that mouse reproductive fitness is actually maintained even when they are housed up to 28 8C [24].…”

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confidence: 99%

Thermoneutrality, Mice, and Cancer: A Heated Opinion

Hylander

Repasky

2016

Trends in Cancer

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“…Scintillation counts from the kinetic experiments were corrected to total body plasma volume or total body mass of each tissue type, respectively. The total plasma volume was estimated from body weight (0.0275 ml plasma/g) (30). One kidney or a weighed aliquot of liver was solubilized.…”

Section: Figurementioning

confidence: 99%