These data indicate that curcumin has nephroprotective properties against cisplatin-induced kidney damage in rats and this effect is associated with its anti-inflammatory and anti-apoptosis profiles, in addition to its antioxidant. Hence, curcumin may be useful for preventing kidney damage against cisplatin administration.
Objective: This study aimed to investigate the efficacy of curcumin (CMN) and nanocurcumin (NC) at preventing cisplatin (CDPP)-induced nephrotoxicity.Methods: Two membrane transporters, copper transporter 1 (CTR1) and organic cation transporter 2 (OCT2), have been identified involved in active accumulation of CDPP into renal tubular cells. We analyzed OCT2 transcription levels in rat kidney tissue and determined whether renoprotective mechanism of CMN involves CTR1. Rats were randomly divided into five groups: (1) Control, (2) CDPP (7 mg/kg as single dose (i.p.), (3) CDPP+CMN (7 mg/kg CDPP as a single dose, i.p.+100 mg/kg/day of CMN), (4) CDPP+50 mg NC (7 mg/kg CDPP as single dose, i.p.+50 mg/kg/day NC), and (5) CDPP+100 mg NC (7 mg/kg CDPP as single dose, i.p.+100 mg/kg/day NC). Quantitative reverse transcription-polymerase chain reaction was performed to calculate relative expression of CTR1 and OCT2 genes in rat kidney.Results: Expression of CTR1 was unassociated with administration of CMN or NC, indicating CTR1 is uninvolved in renoprotective mechanism of CMN. The administration of 100 mg/kg/day NC increased expression of OCT2; this increase was higher compared with normal expression levels. This may be due to another regulatory mechanism from the CMN itself.Conclusion: NC has a better renoprotective effect compared with curcumin, suggested by the increased OCT2 expression on its administration in CDPP-treated rats.
Cisplatin is a platinum-based drug that is usually used for the treatment of many carcinomas. However, it comes with several devastating side effects, including nephrotoxicity. Cisplatin toxicity is a very complex process, which is exacerbated by the accumulation of cisplatin in renal tubular cells via passive diffusion and transporter-mediated processes. Once cisplatin enters these cells, it induces the formation of reactive oxygen species that cause cellular damage, including DNA damage, inflammation, and eventually cell death. On a small scale, these damages can be mitigated by cellular antioxidant defense mechanism. However, on a large scale, such as in chemotherapy, this defense mechanism may fail, resulting in nephrotoxicity. The current article reviews the molecular mechanisms underlying cisplatin-induced nephrotoxicity and possible renoprotective strategies to determine novel therapeutic interventions for alleviating this toxicity.
Background: Nephrotoxicity is a limiting factor of the platinum-based chemotherapeutic drug cisplatin. One third of patient treated with cisplatin eventually develop acute nephrotoxicity due to accumulation of cisplatin in renal tubular cell which causes oxidative stress and DNA damage. Curcumin is the active ingredient of Curcuma longa, which is reported to exhibit anti-inflammatory property and nephroprotective property, despite its low bioavailability. To increase its bioavailability, nanocurcumin can be used instead. This study aims to know the difference between administration of curcumin and nanocurcumin on cisplatin induced acute nephrotoxicity. Methods: Nanocurcumin and curcumin were used in this study on rat model of AKI which induced by cisplatin (n=25) and observe the expression of Nrf2 and Keap1, Oct2 and Ctr1, Kim-1 and Ngal, and curcumin concentration in kidney tissues of rats. Rats were divided into five groups randomly: (1) Control, (2) Cisplatin (7mg/kgBW single dose), (3) Cisplatin + Curcumin (7mg/kgBW single dose + 100mg/kg/day), (4) Cisplatin + 50mg Nanocurcumin (7mg/kgBW single dose + 50mg/kg/day), ( 5) Cisplatin + 100mg Nanocurcumin (7mg/kgBW single dose + 100mg/kg/day). qRT-PCR was then conducted to calculate the relative expression of the genes. LCMS/MS was used to analyze curcumin and nanocurcumin concentration in kidney tissues. Results: There was no significant difference between groups in expression of Nrf2 and Keap1 gene, although there is an increase in Keap1 expression in rats treated with 100mg nanocurcumin. There was also no significant difference in expression of Oct2 and Ctr1 gene, although administration of 100mg Nanocurcumin increases Oct2 gene expression. Kidney damage markers (Kim-1 and Ngal) were also not significantly different between groups, although rats treated with 100mg of Nanocurcumin express lower level of Kim-1 and Ngal. We also found that nanocurcumin 100 mg has a highest concentration accumulation in the kidney tissues compared to that of other groups. Conclusion: Our conclusion is that nanocurcumin have better nephroprotective effect compared to curcumin shown by increase in Keap1 and Oct2 with decreased Kim-1 and Ngal expression in rats treated with 100 mg nanocurcumin at least in part due to increase concentration of 100 mg nanocurcumin in kidney tissues.
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