Protective effect of erythropoietin against cisplatin-induced nephrotoxicity in rats: antigenotoxic and antiapoptotic effect

Rjiba-Touati, Karima; Ayed-Boussema, Imen; Bouaziz, Chayma; Belarbia, A.; Azzabi, A.; Achour, A.; Hassen, Wafa; Bacha, Hassen

doi:10.3109/01480545.2011.589440

Cited by 17 publications

(14 citation statements)

References 48 publications

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“…Olgun et al [25] reported that rhEPO decreased hypoxic-ischemic encephalopathy-induced apoptotic cell death in the cochlea, spiral ganglion, and central auditory pathways of newborn rats and prevented hypoxic-ischemic encephalopathy-induced hearing loss. Rjiba-Touati et al [26] demonstrated that treatment with EPO decreased CDDP-induced apoptotic cell death and tubular injury in rat kidney. They also showed that the antiapoptotic action of EPO was more pronounced when administrated 24 hours before CDDP treatment.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect of Recombinant Human Erythropoietin against Cisplatin-Induced Ototoxicity

Doğan¹,

Olgun²,

Kırkım³

et al. 2015

Int Adv Otol

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OBJECTIVE:To investigate the potential protective effect of recombinant human erythropoietin (rhEPO) against cisplatin-induced ototoxicity. MATERIALS and METHODS:Twenty-eight Wistar albino rats were divided randomly into four groups, and baseline distortion product otoacoustic emission (DPOAE) responses and auditory brainstem response (ABR) thresholds were obtained. Group I received intraperitoneal (i.p.) saline, Group II received a single dose of i.p. 2000 IU/kg rhEPO, and Group III and Group IV received a single dose of i.p. 16 mg/kg cisplatin injection. In Group IV, 2000 IU/kg rhEPO was also injected intraperitoneally two times: 24 hours before and 30 minutes after i.p. 16 mg/kg cisplatin injection. DPOAEs and ABR measurements were repeated 72 hours following cisplatin administration, and the animals were sacrificed. The cochleae of animals were evaluated histopathologically by light microscopy, and percentage of apoptotic cells in the spiral ganglion was then determined by immunofluorescence analysis. RESULTS:Post-treatment auditory assessment revealed significant ABR threshold elevations at click and 6 kHz and 8 kHz frequencies in Group III compared to Groups I and II (p<0.05). In Group III, 8 kHz DPOAEs were also significantly deteriorated compared to Groups I and II (p<0.05). In Group IV, the ABR thresholds and DPOAEs were protected at click and 6 kHz; there was no statistically significant difference between Group IV and Group I at those frequencies. Concomitant administration of rhEPO and cisplatin significantly reduced apoptosis and cell damage. The apoptotic cell percentage of spiral ganglions in Group IV was significantly less than in Group III (p=0.01). CONCLUSION:Our results showed that i.p. application of rhEPO inhibited apoptosis and prevented cisplatin-induced ototoxicity in rats.

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Section: Discussionmentioning

confidence: 99%

The Protective Effect of Recombinant Human Erythropoietin against Cisplatin-Induced Ototoxicity

Doğan¹,

Olgun²,

Kırkım³

et al. 2015

Int Adv Otol

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“…It was reported that EPO ameliorates CP-induced nephrotoxicity [9, 10, 15, 23–26], while female sex hormone, estrogen, inhibits EPO production in female rats [19] and decreases EPO gene expression during hypoxia [20]. Some evidence also has reported the sex difference response to CP-induced nephrotoxicity and renal function [27, 28].…”

Section: Discussionmentioning

confidence: 99%

“…Estrogen decreases hypoxic induction of plasma EPO, and renal EPO gene expression is mediated by increasing NO production [20, 36], and NO can reduce EPO gene expression in kidneys [37]. EPO, as an antioxidant and antiapoptotic agent, has a protective effect against CP-induced nephrotoxicity [14, 23]. Recombinant human EPO reduces the serum levels of MDA and glutathione, induced by CP treatment [38].…”

Section: Discussionmentioning

confidence: 99%

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Estrogen Abolishes Protective Effect of Erythropoietin against Cisplatin-Induced Nephrotoxicity in Ovariectomized Rats

et al. 2012

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Introduction. Nephrotoxicity is one the side effect of cisplatin therapy and erythropoietin has been candidate as a nephroprotectant agent. However, its nephroprotective effect when it is accompained with estrogen has not been studied in female. Methods. 27 ovariectomized female Wistar rats divided into five groups. Groups 1 & 2 received estradiol valerate (0.5 mg/kg/week) for four weeks, and single dose of cisplatin (7 mg/kg, ip) was administrated at the end of week 3. Then the group 1 was treated with erythropoietin (100 U/kg/day), and the group 2 received vehicle during week 4. Groups 3 and 4 were treated similar to group 1 and 2, except for placebo instead estradiol valerate. Group5 (negative control) received placebo during the study. Animals were killed at the end of week 4. Results. In non-erythropoietin treated rats, cisplatin significantly increased the serum levels of blood urea nitrogen and creatinine (P < 0.05). However, these biomarkers significantly decreased by erythropoietin (P < 0.05). The weight loss, kidney weight, and kidney tissue damage score in rats treated with cisplatin but without estradiol were significantly less than the values in similar group when estradiol was present (P < 0.05). Conclusion. It seems that erythropoietin could protect the kidney against cisplatin-induced nephrotoxicity. This protective effect was not observed when estrogen was present.

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“…They concluded that recombinant human erythropoietin administration especially in pretreatment condition protected rats against Cisplatin-induced renal oxidative stress and nephrotoxicity (39). In another study conducted by Rjiba-Touati et al to find the protective effect of erythropoietin against Cisplatin-induced apoptosis in rat kidney, a reduction of apoptosis by up regulation of antiapoptotic protein expressions, down regulation of pro apoptotic protein levels, and reduction of caspase-3 activity in male Wistar rats was seen (40). Hence it seems that the protective action of Eprex on the kidney probably is not directly related to its hematopoietic effects (14).…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin ameliorates genetamicin-induced renal toxicity: A biochemical and histopathological study

et al. 2012

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Background:Investigations have attempted to modify the outcome of tubular injury by either ameliorating renal tubular damage or promoting tubular regeneration in the case of acute tubular necrosis. Objectives: We investigated the protective effect of Eprex an erythropoietin analogue on tubular injury induced by gentamicin (GM). Materials and Methods: Forty male Wistar rats were randomly divided into four groups. In group 1,rats were served as a sham group. In group 2, rats were injected intraperitoneally with 100 mg/kg of GM for 10 consecutive days (positive control group) and then were sacrificed. In group 3, rats received GM for 10 days then Eprex 100U/kg was injected intraperitoneally for the next 10 days and then they were sacrificed at the day 20th. In group 4 rats were injected a combination of GM (80 mg/kg) and Eprex 100U/kg intraperitoneally for 10 days and then were sacrificed. Results: The results indicated that, Eprex prevented the increase in serum creatinine (Cr) and blood urea nitrogen (BUN). The effect of Eprex on damage score, showed that co-administration of GM and Eprex (group 3 and 4) reduced the kidney tissue damage compared to positive control group (P<0.05). This result indicat that Eprex potentially can reduce or prevent the kidney tissue damage. Conclusions: Ameliorative effect of Eprex when the drug was given in combination with GM and also when the drug was applied after GM-induced tubular damage, revealed the renoprotective potency of Eprex. Eprex is a promising drug to prevent or attenuate tubular damage induced by GM or other nephrotoxic agents which act through the same mechanisms as gentamicin.

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Protective effect of erythropoietin against cisplatin-induced nephrotoxicity in rats: antigenotoxic and antiapoptotic effect

Cited by 17 publications

References 48 publications

The Protective Effect of Recombinant Human Erythropoietin against Cisplatin-Induced Ototoxicity

The Protective Effect of Recombinant Human Erythropoietin against Cisplatin-Induced Ototoxicity

Estrogen Abolishes Protective Effect of Erythropoietin against Cisplatin-Induced Nephrotoxicity in Ovariectomized Rats

Erythropoietin ameliorates genetamicin-induced renal toxicity: A biochemical and histopathological study

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