Role of glutathione in acute N-(3,5-dichlorophenyl) succinimide-induced nephrotoxicity in Sprague-Dawley and Fischer 344 rats

Yang, David J.; Teets, Vonda J.; Bolton, Barbara; Brown, Patrick I.; Rankin, Gary O.

doi:10.1016/0300-483x(87)90112-0

Cited by 25 publications

(7 citation statements)

References 29 publications

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“…This conclusion is based on the previous finding that pretreatments (DEM, BSO) that would reduce renal LTC 4 formation (Yang et al, 1987; Rankin et al, 1990; 1991b) and the current work with the 5-lipoxygenase synthesis inhibitor DEC all produced marked attenuation of NDPS and NDPS metabolite nephrotoxicity, while the LTD 4 receptor blocker LY171883 was fairly ineffective at attenuating NDPS metabolite nephrotoxicity. In addition, the γ-glutamyl transpeptidase inhibitor, AT-125 (acivicin), which would be expected to reduce the conversion of LTC 4 to LTD 4 did not attenuate NDPS nephrotoxicity (Rankin et al, 1991a).…”

Section: Discussionmentioning

confidence: 72%

“…These results indicated that glutathione plays a role in mediating NDPS nephrotoxicity, and we have found this response is not related to the formation of nephrotoxic NDPS metabolites (Rankin et al, 1991a). However, the ability of pretreatments such as DEM or BSO, pretreatments that would reduce the formation of vasoconstrictor leukotrienes, to reduce NDPS and NDPS metabolite nephrotoxicity (Yang et al, 1987; Rankin 1990; 1991b) suggested that the renal vasoconstrictor leukotrienes LTC 4 and/or LTD 4 might be contributing to the mechanisms of NDPS nephrotoxicity. The ability of DEC, a 5-lipoxgenase inhibitor, to markedly attenuate NDPS nephrotoxicity adds further evidence that leukotrienes contribute to NDPS-induced nephropathy.…”

Section: Discussionmentioning

confidence: 99%

“…The right kidney was quartered and placed in 10% neutral buffered formalin. Tissues from NDPS metabolite treated and control rats were examined using light microscopy for evidence of chemically induced morphological changes as previously described (Yang et al, 1987). …”

Section: Methodsmentioning

confidence: 99%

“…Henesey et al (1999) found covalently bound NDPS-derived radioactivity in higher concentrations in kidney than in liver or plasma, which supported the renal accumulation of hepatic-derived reactive NDPS metabolites. Surprisingly, NDPS administration at nephrotoxic doses does not markedly deplete renal or hepatic glutathione (Yang et al, 1987) and depletion of glutathione with diethyl maleate (DEM) (Yang et al, 1987) or inhibition of glutathione synthesis with buthionine sulfoximine (BSO) is protective rather than potentiating NDPS and NDPS metabolite nephrotoxicity (Rankin et al, 1990; 1991b). It does not appear that decreasing the formation of a nephrotoxic glutathione conjugate of NDPS can explain the mechanisms for how reduced glutathione concentrations attenuates NDPS or NDPS metabolite nephrotoxicity (Rankin et al, 1991a).…”

Section: Introductionmentioning

confidence: 99%

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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: 72%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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 IRCC model was chosen for study because many of our recent studies on chloroaniline nephrotoxicity have used this model [25]. The Fischer 344 rat was chosen because this rat strain responds to nephrotoxicants more like humans than other rat strains [26]. …”

Section: Introductionmentioning

confidence: 99%

Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro

Rankin¹,

Tyree²,

Pope³

et al. 2017

IJMS

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This study determined the comparative nephrotoxic potential of four trichloronitrobenzenes (TCNBs) (2,3,4-; 2,4,5-; 2,4,6-; and 3,4,5-TCNB) and explored the effects of antioxidants and biotransformation inhibitors on TCNB-induced cytotoxicity in isolated renal cortical cells (IRCC) from male Fischer 344 rats. IRCC were incubated with a TCNB up to 1.0 mM for 15–120 min. Pretreatment with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), or peroxidase inhibitor was used in some experiments. Among the four TCNBs, the order of decreasing nephrotoxic potential was approximately 3,4,5- > 2,4,6- > 2,3,4- > 2,4,5-TCNB. The four TCNBs exhibited a similar profile of attenuation of cytotoxicity in response to antioxidant pretreatments. 2,3,4- and 3,4,5-TCNB cytotoxicity was attenuated by most of the biotransformation inhibitors tested, 2,4,5-TCNB cytotoxicity was only inhibited by isoniazid (CYP 2E1 inhibitor), and 2,4,6-TCNB-induced cytotoxicity was inhibited by one CYP inhibitor, one FMO inhibitor, and one peroxidase inhibitor. All of the CYP specific inhibitors tested offered some attenuation of 3,4,5-TCNB cytotoxicity. These results indicate that 3,4,5-TCNB is the most potent nephrotoxicant, free radicals play a role in the TCNB cytotoxicity, and the role of biotransformation in TCNB nephrotoxicity in vitro is variable and dependent on the position of the chloro groups.

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Cyclization of a cysteine conjugate of N‐(3,5‐Dichlorophenyl)succinimide

Shih¹,

Rankin²

1988

Journal of Heterocyclic Chem

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N‐(3,5‐Dichlorophenyl)‐2‐cysteinylsuccinimide methyl ester hydrochloride (5) was prepared from N‐(3,5‐dichlorophenyl)maleimide (3) and cysteinyl methyl ester hydrochloride. Attempted neutralization of the cysteine conjugate salt with triethylamine resulted in spontaneous cyclization of 5 to form the more stable 2‐(N‐3,5‐dichlorophenylcarbamoylmethyl)‐5‐carbomethoxy‐1,4‐thiazine‐ 3‐one (6). Similar results might be expected in vivo should these metabolites of succinimides be formed.

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Role of glutathione in acute N-(3,5-dichlorophenyl) succinimide-induced nephrotoxicity in Sprague-Dawley and Fischer 344 rats

Cited by 25 publications

References 29 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

Role of Free Radicals and Biotransformation in Trichloronitrobenzene-Induced Nephrotoxicity In Vitro

Cyclization of a cysteine conjugate of N‐(3,5‐Dichlorophenyl)succinimide

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