Effect of dimethyl sulfoxide on N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity

Rankin, Gary O.; Beers, K. W.; Nicoll, Derek W.; Anestis, Dianne K.; Ball, John G.; Valentovic, Monica; Brown, Patrick I.

doi:10.1016/0300-483x(95)93709-d

Cited by 4 publications

(2 citation statements)

References 25 publications

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“…The ability of DEC, a 5-lipoxgenase inhibitor, to markedly attenuate NDPS nephrotoxicity adds further evidence that leukotrienes contribute to NDPS-induced nephropathy. The finding that DEC also blocks NDHS and 2-NDHSA nephrotoxicity provides evidence that DEC was not merely blocking the metabolism of NDPS as seen with some other protective agents (Rankin et al, 1991a; Rankin et al, 1995). …”

Section: Discussionmentioning

confidence: 82%

Role of leukotrienes in N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity in male Fischer 344 rats

Rankin¹,

Hong²,

Anestis³

et al. 2012

Toxicology

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The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) can induce marked nephrotoxicity in rats following a single intraperitoneal (ip) administration of 0.4 mmol/kg or greater. Although NDPS induces direct renal proximal tubular toxicity, a role for renal vascular effects may also be present. The purpose of this study was to examine the possible role of vasoconstrictor leukotrienes in NDPS and NDPS metabolite nephrotoxicity. Male Fischer 344 rats (4 rats/group) were administered diethylcarbamazine (DEC; 250 or 500 mg/kg, ip), an inhibitor of LTA4 synthesis, 1h before NDPS (0.4 mmol/kg, ip), N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS, 0.1, 0.2, or 0.4 mmol/kg, ip), or N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA, 0.1 mmol/kg, ip) or vehicle. In a separate set of experiments, the LTD4 receptor antagonist LY171883 (100 mg/kg, po) was administered 0.5 h before and again 6 h after NDHS (0.1 mmol/kg, ip) or 2-NDHSA (0.1 mmol/kg, ip) or vehicle. Renal function was monitored for 48 h post-NDPS or NDPS metabolite. DEC markedly reduced the nephrotoxicity induced by NDPS and its metabolites, while LY171883 treatments provided only partial attenuation of NDHS and 2-NDHSA nephrotoxicity. These results suggest that leukotrienes contribute to the mechanisms of NDPS nephrotoxicity.

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Section: Discussionmentioning

confidence: 82%

Role of leukotrienes in N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity in male Fischer 344 rats

Rankin¹,

Hong²,

Anestis³

et al. 2012

Toxicology

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“…promotion of cyclization to NDHS) suggested the need to ¼nd a vehicle that did not require heating to dissolve 2-or 3-NDHSA prior to injection. Studies found that up to 12.5-25% DMSO in sesame oil as a vehicle did not require heating to affect solution and did not alter the nephrotoxic potential of 2-NDHS or NDHS (Hong et al, 1998;Rankin et al, 1995). We have also recently determined that in male Fischer 344 rats, 3-NDHSA in 12.5% DMSO in sesame oil as the vehicle is equipotent as a nephrotoxicant to 3-NDHSA in 12.5% DMSO in corn oil as seen in this study (unpublished results).…”

Section: Discussionmentioning

confidence: 99%

Nephrotoxicity induced by N‐(3,5‐dichlorophenyl)‐3‐hydroxysuccinamic acid in male and female Fischer 344 rats

Rankin

Hong

Anestis

2008

J of Applied Toxicology

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The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is a more potent nephrotoxicant in female rats than in males. Similarly, nephrotoxicant NDPS metabolites studied to date in male and female rats have also demonstrated gender differences, being twice as potent as nephrotoxicants in females as in males. The purpose of this study was to examine the nephrotoxic potential of N-(3,5-dichlorophenyl)-3-hydroxysuccinimide (3-NDHSA) in male and female Fisher 344 rats to determine if gender differences in nephrotoxic potential also exist for this metabolite. Rats (four per group) were administered a single intraperitoneal (i.p.) injection of 3-NDHSA (0.1, 0.2 or 0.4 mmol kg(-1)) or vehicle, and renal function was monitored at 24 and 48 h. 3-NDHSA 0.1 mmol kg(-1) did not induce nephrotoxicity in male or female rats. In male rats, 3-NDHSA 0.2 mmol kg(-1) induced mild nephrotoxicity seen as diuresis and transient, mild proteinuria. However, 3-NDHSA 0.4 mmol kg(-1) induced marked nephrotoxicity. In female rats, 3-NDHSA 0.2 mmol kg(-1) induced mild nephrotoxicity, as evidenced by transient diuresis and proteinuria. As in males, 3-NDHSA 0.4 mmol kg(-1) induced marked nephrotoxicity. These results indicate that, unlike NDPS and other nephrotoxic NDPS metabolites, 3-NDHSA does not exhibit gender differences in nephrotoxic potential. In addition, in comparison with NDPS and other nephrotoxic NDPS metabolites, 3-NDHSA is a less potent nephrotoxicant that NDHS or 2-NDHSA and similar to NDPS in nephrotoxic potential in male rats.

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A comparison of clinical, histopathological and cell-cycle markers in rats receiving the fungal toxins fumonisin B1 or fumonisin B2 by intraperitoneal injection

Bondy

Barker

Lombaert

et al. 2000

Food and Chemical Toxicology

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Effect of dimethyl sulfoxide on N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity

Cited by 4 publications

References 25 publications

Role of leukotrienes in N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity in male Fischer 344 rats

Role of leukotrienes in N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity in male Fischer 344 rats

Nephrotoxicity induced by N‐(3,5‐dichlorophenyl)‐3‐hydroxysuccinamic acid in male and female Fischer 344 rats

A comparison of clinical, histopathological and cell-cycle markers in rats receiving the fungal toxins fumonisin B1 or fumonisin B2 by intraperitoneal injection

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