Comparative nephrotoxicity of carboplatin and cisplatin in euvolemic and dehydrated rats

Martinez, F.; Deray, Gilbert; Dubois, Michelle; Beaufils, H; Jacquiaud, Claude; Bourbouze, Richard; Benhmida, Mohamed; Jaudon, M C; Jacobs, C

doi:10.1097/00001813-199302000-00011

Cited by 17 publications

(5 citation statements)

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“…C. aurantium reversed the values to near normalcy as it is evident in results section. Our results are in line with the previous findings that showed the disturbances in abovementioned parameters [46, 47].…”

Section: Discussionsupporting

confidence: 94%

Citrus aurantium Ameliorates Cisplatin-Induced Nephrotoxicity

Wang

Hassan

Ahmad

et al. 2019

BioMed Research International

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We aimed to study the effects of Citrus aurantium (C. aurantium) on renal functions in cisplatin-induced nephrotoxicity in rats. The study involved male Wistar rats weighing 250–300 g that were fed and kept under standard conditions. Rats were randomly divided into control, cisplatin administered, C. aurantium 200 mg/kg, and C. aurantium 400 mg/kg groups. Cisplatin was administered at 5 mg/kg i.p. once at the start of study to induce nephrotoxicity. Blood and urine samples were obtained at alternative days for analysis. The body weight and urine output were monitored at regular intervals. Plasma and urinary sodium, potassium, and creatinine levels were measured at the end of study duration. Absolute excretion of sodium and potassium; sodium to potassium ratio; kidney weights; fractional excretion of sodium and potassium; and absolute creatinine clearance were determined to analyze the effects of C. aurantium. Histopathological changes of kidney tissues were studied to determine relevant effects. The results indicate that cisplatin lowered the total body weights while raising the urinary output and kidney weights, reversed by C. aurantium both dose and time dependently. Similarly, C. aurantium markedly normalized plasma, urinary sodium, potassium, and creatinine levels. Cisplatin-induced absolute sodium clearance, absolute potassium clearance, absolute creatinine clearance, sodium to potassium ratio, and fractional excretion of sodium and potassium were significantly reversed by C. aurantium. Histopathological analysis showed notable improvement in C. aurantium administered groups as compared to cisplatin-induced group. Study suggests that C. aurantium possesses excellent nephroprotective effects against cisplatin-induced toxicity.

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Section: Discussionsupporting

confidence: 94%

Citrus aurantium Ameliorates Cisplatin-Induced Nephrotoxicity

Wang

Hassan

Ahmad

et al. 2019

BioMed Research International

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“…These doses are equivalent to the clinical therapeutic doses of carboplatin in cancer patients (Bishop 1992;Bohm et al 1999;Wandt et al 1999;Maldoon et al 2000). However, administration of high and/or cumulative doses of carboplatin produced renal toxicity in humans (Agraharkar et al 1998;English et al 1999) and experimental animals (Ueda et al 1991;Martinez et al 1993). The data show that carboplatin in single high doses (192 and 256 mg/ kg) caused renal dysfunction in rats as evidenced by elevation of plasma creatinine and blood urea nitrogen levels.…”

Section: Discussionmentioning

confidence: 99%

Dose Response of Carboplatin‐Induced Nephrotoxicity in Rats

Husain¹,

Jagannathan²,

Hasan³

et al. 2002

Pharmacology & Toxicology

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Carboplatin, a second-generation platinum-containing anticancer drug, is currently being used against a variety of cancers. High-dose carboplatin chemotherapy can cause renal tubular injury in cancer patients. However, the biochemical mechanism of carboplatin-induced renal injury has not been well studied. This study investigated the dose response of carboplatin-induced changes in endogenous antioxidants, lipid peroxidation and platinum content in rat kidney. Male Wistar rats (250-300 g) were divided into five groups and treated as follows: (1) control (saline, intraperitoneally); (2) carboplatin (64 mg/kg, intraperitoneally); (3) carboplatin (128 mg/kg, intraperitoneally); (4) carboplatin (192 mg/kg, intraperitoneally); and (5) carboplatin (256 mg/kg, intraperitoneally). The animals were sacrificed four days after treatment. The blood and kidneys were isolated and analyzed. Plasma creatinine and blood urea nitrogen levels were increased significantly in response to carboplatin in a dose-dependent manner. Renal superoxide dismutase and catalase activities were decreased significantly due to carboplatin at dosages of 128 mg/kg and above. The protein expressions of renal copper/zinc-superoxide dismutase and manganese-superoxide dismutase significantly depleted after carboplatin. Carboplatin (192 and 256 mg/kg) significantly increased lipid peroxidation (malondialdehyde concentration) in rat kidneys. Carboplatin dose-dependently increased the renal platinum concentration, with significance at dosages of 128 mg/kg and above. Carboplatin (256 mg/kg) significantly increased renal xanthine oxidase activity, while ratio of reduced to oxidized glutathione depleted significantly. The data suggested that carboplatin caused dose-dependent oxidative renal injury, as evidenced by renal antioxidant depletion, enhanced lipid peroxidation, platinum content, plasma creatinine and blood urea nitrogen levels in rats.

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“…For example, renal transporters and tissue accumulation are believed to play a role in platinum nephrotoxicity ( Pabla and Dong, 2008 ). Carboplatin, a cisplatin analog has reduced nephrotoxicity and is proposed to be a result of reduced transporter interaction and protein binding ( Małyszko et al , 2017 ; Martinez et al , 1993 ). Zebrafish exposed to Pt(CN) 4 2− up to 1000 µM showed no signs of toxicity or gross morphological, far above the efficacious dose for complexes 1–4 ( Nath et al , 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Investigating the replacement of carboxylates with carboxamides to modulate the safety and efficacy of platinum(II) thioether cyanide scavengers

Behymer,

Mo,

Fujii

et al. 2023

Toxicological Sciences

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Cyanide represents a persistent threat for accidental or malicious misuse due to easy conversion into a toxic gas and access to large quantities through several industries. The high safety index of hydroxocobalamin is a cornerstone quality as a cyanide scavenger. Unfortunately, intravenous infusion of hydroxocobalamin limits the utility in a mass casualty setting. We previously reported platinum(II) [Pt(II)] complexes with trans-directing sulfur ligands as an efficacious alternative to hydroxocobalamin when delivered by a bolus intramuscular injection in mice and rabbits. Thus, to enable Pt(II) as an alternative to hydroxocobalamin, a high safety factor is needed. The objective is to maintain efficacy and mitigate the risk for nephrotoxicity. Platinum amino acid complexes with the ability to form five- or six-membered rings and possessing either carboxylates or carboxamides are evaluated in vitro for cyanide scavenging. In vivo efficacy was evaulated in the zebrafish and mice cyanide exposure models. In addition, Pt(II) complex toxicity and pharmacokinetics were evaluated in a cyanide naive Sprague-Dawley model. Doses for toxicity are escalated to 5x from the efficacious dose in mice using a body surface area adjustment. The results show the carboxamide ligands display a time and pH dependence on cyanide scavenging in vitro and efficacy in vivo. Additionally, exchanging the carboxylate for carboxamide showed reduced indications of renal injury. A pharmacokinetic analysis of the larger bidentate complexes displayed rapid absorption by intramuscular administration and having similar plasma exposure. These findings point to the importance of pH and ligand structures for methionine carboxamide complexes with Pt(II).

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Comparative nephrotoxicity of carboplatin and cisplatin in euvolemic and dehydrated rats

Cited by 17 publications

References 0 publications

Citrus aurantium Ameliorates Cisplatin-Induced Nephrotoxicity

Citrus aurantium Ameliorates Cisplatin-Induced Nephrotoxicity

Dose Response of Carboplatin‐Induced Nephrotoxicity in Rats

Investigating the replacement of carboxylates with carboxamides to modulate the safety and efficacy of platinum(II) thioether cyanide scavengers

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