Cisplatin nephrotoxicity affects magnesium and calcium metabolism

Abstract

Cisplatin is not directly toxic to bone, but cisplatin nephrotoxicity leading to magnesium wasting may affect magnesium and calcium metabolism, both of which contribute to bone integrity. The specificity of the magnesium lesion suggests that cisplatin may have an affinity for proteins that regulate magnesium absorption. Sulfhydryls such as amifostine can reduce the toxicity of cisplatin in adults, but current pediatric data do not indicate a role for sulfhydryl therapy to reduce cisplatin toxicity in children.

Renoprotective Effects of Fermented Black Ginseng through Ameliorating Oxidative Stress Associated with Cisplatin-Induced Acute Nephrotoxicity in Mice

“…Similary, the renal GSH level by WG or FBG pretreatment was increased higher than it of normal mice. Especially, FBG administration showed a significant increase (p<0.05) [34,35].…”

“…NF-κB is a major proinflammatory transcriptional factor sequestered in the cytoplasm by the inhibitor protein IκBα. Phosphorylation of IκBα leads to the release of NF-κBand then NF-κB translocates to the nucleus and promotes the transcription of target genes including inflammatory mediators and cytokines such as COX-2, iNOS, TNF-α and IL-6 [35,37]. Figure 5 shows p-IκBα and NF-κBp65 protein expressions.…”

Nephrotoxicity of platinum derivatives in children – a review of the literature

“…Clinical and experimental studies have shown that CDDP interferes with magnesium transport, predominantly in the distal tubules [17][18][19]. Hypomagnesaemia caused by CDDP administration may persist for a few years after the end of therapy [20][21][22][23] and, in 1/3 to 2/3 children, may become permanent [21,24].…”

“…CDDPrelated hypocalcaemia is resistant to equalisation with only calcium supplementation. The mechanism of hypocalcaemia secondary to hypomagnesaemia implies that normalisation of the calcium level may be achieved only through simultaneous magnesium and calcium substitution [20]. In addition to hypomagnesaemia and hypocalcaemia, patients may also present with hypokalaemia [25] and, very rarely, hyponatraemia (renal salt-wasting syndrome) [26,27].…”

“…Almost 90% of the administered dose is filtered through the kidneys [20]. Moreover, contrary to CDDP, CBD-CA is not transformed into toxic metabolic compounds in renal tubule cells [10].…”