Key result
Curcumin sensitized leiomyosarcoma cells to cisplatin and protected nephron histology in rats, but failed to preserve antioxidant enzyme activity against cisplatin-induced nephrotoxicity.
Why the study?
Cisplatin causes nephrotoxicity by generating free radicals and impairing antioxidant enzymes, making modulation of oxidative stress with antioxidant molecules an attractive strategy to minimize side effects.
Does curcumin sensitize LMS cells to cisplatin and protect against cisplatin-induced nephrotoxicity in rats?
Does curcumin sensitize LMS cells to cisplatin and protect against cisplatin-induced nephrotoxicity in rats?
Curcumin acts as a chemosensitizer for leiomyosarcoma cells and protects nephron histology from cisplatin toxicity, but does not mediate antioxidant enzyme activity in vivo.
This is the authors' abstract. We don't add key points for this paper.
Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney’s relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats’ blood and malondialdehyde levels in rats’ urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood’s antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons’ histology from cisplatin’s toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.
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Antioxidants may attenuate cisplatin nephrotoxicity; leaves open which agents and doses merit clinical testing.
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Dhima et al. (2019) studied Leiomyosarcoma and cisplatin-induced nephrotoxicity. Curcumin was evaluated on Apoptosis, mitochondrial function, and renal injury markers. Curcumin sensitized leiomyosarcoma cells to cisplatin and protected nephron histology in rats, but failed to preserve antioxidant enzyme activity against cisplatin-induced nephrotoxicity.
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