Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

Perše, Martina; Večerić-Haler, Željka

doi:10.1155/2018/1462802

Cited by 169 publications

(172 citation statements)

References 189 publications

(220 reference statements)

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“…clinical markers for renal tissue injury, including the levels of serum Bun and Scr, were investigated to evaluate cP-induced nephrotoxicity. it has previously been reported that a single dose of cP (3-8 mg/kg) can cause acute nephrotoxicity and induce changes to kidney structure and function in rats (32). in the present study, animal models of cP-induced aKi were established by i.p.…”

Section: Resultsmentioning

confidence: 78%

“…Dex treatment ameliorates CP-induced apoptosis of tubular epithelial cells. apoptotic cell death is the major pathological process which renal tissue undergoes as a result of cP toxicity (32). To investigate whether dex protected renal tubular epithelial cells against apoptosis induced by cP, tubular cell apoptosis was detected in the present cP-induced aKi model using Tunel assay.…”

Section: Resultsmentioning

confidence: 97%

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Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Chai

Zhu

et al. 2020

Mol Med Report

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cisplatin (cP) is an effective antineoplastic agent; however, cP-induced acute kidney injury (aKi) seriously affects the prognosis of patients with cancer. endoplasmic reticulum (er) stress (erS)-induced apoptosis serves a pivotal role in the pathogenesis of cP-induced aKi. dexmedetomidine (dex), a potent α 2 adrenergic agonist, has been reported to exert protective effects against aKi. However, the protective effects of dex against cP-induced aKi and the potential molecular mechanisms remain unknown. in the present study, male Sprague-dawley rats were divided into four groups (n=10/group), as follows: control group; cP group, rats received an intraperitoneal (i.p.) injection of 5 mg/kg cP; dex + cP group, rats received an i.p. injection of 25 µg/kg dex immediately after cP treatment; and dex + cP + atipamezole (atip) group, rats received an i.p. injection of 250 µg/kg atip, an α 2 adrenoreceptor (α 2 ar) antagonist, and then received the same treatment as the dex + cP group. rats were anesthetized and sacrificed 96 h after CP injection. Subsequently, serum blood urea nitrogen (Bun) and serum creatinine (Scr) were analyzed, and kidney samples were collected for analyses. Pathological changes were examined using hematoxylin and eosin staining, and protein expression levels were assessed using western blotting and immunohistochemical staining. in addition, apoptosis was examined using a terminal deoxynucleotidyl transferase duTP nick-end labeling assay. The present results suggested that dex protected against cP-induced aKi by attenuating histological changes in the kidney, serum Bun and Scr production. Furthermore, the expression levels of 78-kda glucose-regulated protein, c/eBP homologous protein and caspase-12, and the apoptotic rate in the kidney were decreased following dex treatment. in addition, the expression levels of phosphorylated (p)-Pi3K and p-aKT in the dex + cP group were significantly increased. Conversely, the renoprotective effects of dex were attenuated following the addition of atip. in conclusion, dex may alleviate cP-induced aKi by attenuating erS-induced apoptosis, at least in part, via the α 2 ar/Pi3K/aKT signaling pathway.

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Section: Resultsmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 97%

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Chai

Zhu

et al. 2020

Mol Med Report

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“…Despite intense prophylactic attempts, nephrotoxicity has been reported even in 20%-30% of patients who received a single dose of cisplatin [1]. As renal toxicity is accepted to be cumulative, it is suggested that successive use of cisplatin would increase the incidence and severity of toxicity [6].…”

mentioning

confidence: 99%

The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin induced nephrotoxicity: A rat model

2019

Turk J Med Sci

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Introduction Cisplatin is one of the most effective chemotherapeutic agents used for the treatment of solid tumors. Despite its antitumor activity, it is also known for serious side effects. Major side effects include nephrotoxicity, neurotoxicity, and myelosuppression, and among these, the most serious and dose-limiting side effect that limits its clinical use and anticancer activity is nephrotoxicity. Despite its toxic characteristics, it is still widely used thanks to its therapeutic efficacy considering its risk/benefit ratio [1]. While cisplatin interacts with many cell components, the main biological target of the drug is deoxyribonucleic acid (DNA) [2]. However, as proximal tubule cells are nondividing cells, the nephrotoxic effect is believed to occur via mechanisms other than DNA damage. While different mechanisms are suggested for the development of nephrotoxicity, the most commonly accepted and investigated mechanisms are apoptosis, oxidative stress, and inflammation [3]. As no approved treatment protocol or specific antidote to be used against possible toxic effects of cisplatin use currently exists [4], different toxicity-preventing strategies are being rigorously investigated today. Routine applications to prevent nephrotoxicity include creating forced diuresis using mannitol and furosemide, using hypertonic chlorine solutions, using alternative cisplatin regimens, avoiding combination with other nephrotoxic agents, and using it together with compounds thought to be able to prevent nephrotoxicity [5]. Background/Aim: Cisplatin is a highly effective chemotherapeutic agent used in the treatment of solid organ cancers. Besides its chemotherapeutic effectiveness, cisplatin administration is associated with numerous side effects. Of those, the most clinically significant and common effect is nephrotoxicity. Recent studies reported that oxidative stress and inflammation are probably the most important mechanisms that contribute to the nephrotoxicity. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent. In the present study, the effects of NAC on cisplatin-induced nephrotoxicity were investigated. Materials and methods: Rats were divided into four groups each including eight rats: CONT, NAC-250, CP, and CP+NAC. Rats in experimental groups were treated intraperitoneally (i.p.) with a single dose of cisplatin (10 mg/kg body weight) and i.p. with NAC (250 mg/kg body weight) for three consecutive days. Nephrotoxicity was determined by plasma BUN and creatinine levels. In tissue samples, myeloperoxidase (MPO), nuclear factor-kappa B (NF-kB), high mobility group box-1 (HMGB-1), total oxidant status (TOS), and total antioxidant status (TAS) levels were measured. Kidneys were analyzed histopathologically as well. Results: It was revealed that cisplatin was not effective on MPO, HMGB-1 and NF-kB levels but did increase TOS levels and decrease TAS levels in tissue samples. Interestingly, NAC elevated MPO and HMGB-1 levels significantly. Nevertheless, NAC ameliorated histological and functional change...

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“…Cisplatin is known to demonstrate toxic effects on the renal tubule, vasculature, and glomeruli. It results in structural damage to the kidney and consequently increases creatinine and urea in blood [37][38][39]. Panaxynol treatment reduced the serum creatinine and BUN in mice with cisplatin-induced kidney injury.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

Lee

Vu-Huynh

et al. 2019

Biomolecules

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Polyacetylenic compounds isolated from Panax species are comprised of non-polar C17 compounds, exhibiting anti-inflammatory, antitumor, and antifungal activities. Panaxynol represents the major component of the essential oils of ginseng. We investigated whether panaxynol isolated from Panax vietnamensis (Vietnamese ginseng, VG) could prevent cisplatin-induced renal damage induced in vitro and in vivo. Cisplatin-induced apoptotic cell death was observed by staining with annexin V conjugated with Alexa Fluor 488, and western blotting evaluated the molecular mechanism. Panaxynol at concentrations above 0.25 μM prevented cisplatin-induced LLC-PK1 porcine renal proximal tubular cell death. LLC-PK1 cells treated with cisplatin demonstrated an increase in apoptotic cell death, whereas pretreatment with 2 and 4 μM panaxynol decreased this effect. Cisplatin demonstrated a marked increase in the phosphorylation of c-Jun N-terminal kinase (JNK), P38, and cleaved caspase-3. However, pretreatment with 2 and 4 μM panaxynol reversed the upregulated phosphorylation of JNK, P38, and the expression of cleaved caspase-3. We confirmed that the protective effect of panaxynol isolated from P. vietnamensis in LLC-PK1 cells was at least partially mediated by reducing the cisplatin-induced apoptotic damage. In the animal study, panaxynol treatment ameliorated body weight loss and blood renal function markers and downregulated the mRNA expression of inflammatory mediators.

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Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

Cited by 169 publications

References 189 publications

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin induced nephrotoxicity: A rat model

Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

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