Carnitine Deficiency: A Causative Clue or a Sequel in Carboplatin Myelosuppression

Abstract

We have previously demonstrated that carnitine deficiency aggravated paracetamol-induced hepatopathy and carboplatin-induced nephropathy. As a continuum, we have addressed in the current study as to whether carboplatin-induced myelosuppression would be exacerbated by carnitine deficiency. Challenging male Wistar rats with a single dose of carboplatin (35 mg/kg, IP) induced bone marrow suppression manifested as anemia, leucopenia, thrombocytopenia as well as increased frequencies of the micronucleated bone marrow cells; MPCE and MNCE with notable reduction in the P/N ratio. The platinum drug also elevated serum TNF-a and reduced serum free and total carnitine levels. Besides, ATP levels in red and T cells were lowered. Likewise, the mitochondrial membrane potential in T lymphocytes was reduced following the use of the potentiometric dye; JC-1, and this was well correlated with cellular ATP production. Carnitine deficiency exacerbated carboplatin myelotoxicity as it exaggerated all biochemical, hematological and cytogenetic parameters. To address as to whether carnitine deficiency was a causative clue or merely a sequel of carboplatin myelotoxicity, L-carnitine was supplemented ahead of carboplatin challenege. Herein, L-carnitine mitigated all the biochemical, hematological and cytogenetic effects possibly via modulating the release of TNF-a, cellular ATP production and restoring the mitochondrial membrane potential. Irrespective of the mechanisms involved, the current results may afford the potential role for carnitine supplementation as add-on nutraceutical in carboplatin-based chemotherapy.

Paclitaxel-carboplatin chemotherapy induced hematologic toxicities among epithelial ovarian cancer patients

“…(17,18) It also seems that carboplatin may increase serum TNF-α, suppressing the development of hematologic progenitor cells. (19) Currently, genetic polymorphisms are being investigated to determine their association with paclitaxel-carboplatin hematologic toxicity, depending on race and ethnicity. The single nucleotide polymorphisms 2677G>T/A and 3435C>T of ABCB1 genes have been associated with neutropenia in paclitaxel chemotherapy in EOC cases in some studies, (20,21) but no association has been found in others.…”