Biochemical and Pharmacological Effects of Mitoxantrone and Acetyl-L-Carnitine in Mice with a Solid Form of Ehrlich Tumour

Abstract

Background: Dysfunction of the carnitine system in non-tumour tissue following anticancer therapy has been reported. In this setting, supplementation with carnitine derivatives might increase the general metabolic activity of normal cells so that they might better withstand the adverse effects of chemotherapy aimed at tumour cells. Here we investigated the effect of acetyl-L-carnitine (ALC) alone and in combination with the antineoplastic agent mitoxantrone (MX) in an animal cancer model. Methods: The effects of MX and MX-ALC were assessed based on gain or loss of body weight and on local growth of a solid form of Ehrlich tumour inoculated into mice. We also performed biochemical analyses like serum activities of some enzymes signalling the functioning of the liver, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Total protein, albumin and bilirubin were also determined in serum. Under favourable conditions, the Ehrlich tumour readily forms metastases, and this is the reason why we performed histological studies of samples of both the liver and heart in order to identify changes that may have mediated the observed effect of the treatment. In addition to those studies, the survival time of treated animals against controls was also noted. Results: MX monotherapy was associated with lower body weight gain, fewer metastases, smaller tumour size, and lower dissemination. ALC alone promoted survival, but had no potentiating effect on MX therapy in terms of survival. Serum biochemistry changes associated with MX-ALC treatment consisted of a significant (p < 0.05) increase in AST with MX at 6 or 9 mg·kg^–1 plus ALC 200 mg·kg^–1 and a significant (p < 0.05) reduction in total protein compared to the corresponding MX group; serum albumin and bilirubin remained unchanged. Conclusion: ALC in combination with MX, regardless of the dose of MX, led to higher occurrences of metastases with dissemination to the kidneys, lungs, heart, and mediastinum compared to MX treatment alone. These histological findings indicate that ALC is inappropriate to combine with MX in the treatment of a solid cancer. The protective effect of ALC in combination therapy with the cytostatic drug MX was not supported in this study by our findings that the agent did not improve the therapeutic outcomes of MX therapy.

L-Carnitine Ameliorates L-Asparaginase-Induced Acute Liver Toxicity in Steatotic Rat Livers

“…In contrast, the combination of L -carnitine with mitoxantrone in a mouse solid tumor model of Ehrlich tumor did not show a beneficial effect of L -carnitine. Here, Niang et al [48] reported a negative effect of L -carnitine on the therapeutic outcome of mitoxantrone. …”

Biochemical and Pharmacological Effects of Mitoxantrone and Acetyl-LCarnitine in Mice with a Solid Form of Ehrlich Tumour

“…Those higher doses, however, were associated with greater inhibitory effect on the growth of STE. Repeated doses of ALC alone were beneficial and produced a mean survival of 28.26 days (95% CI 19.21-41.57), about 58.8% longer than the untreated STE control group (17.81 days) [17]. Signs of toxicity in our experiments included decreased body weight gain and body weight loss.…”

Cancer Preventive Effects of Whole Cell Type Immunization against Mice Ehrlich Tumors

“…Ehrlich tumors are used largely in experimental cancer treatment, prevention, and modeling studies because tumor ocurrence rates after transplantation is very high and tumor growth is extremely rapid. On the other hand, a number of studies related to prevention of Ehrlich tumor (either ascites or solid subtypes) are few (Mashanova et al, 2010;Jukanti et al, 2011;Niang et al, 2011;Salem et al, 2011).…”