Carnitine protects mitochondria and removes toxic acyls from xenobiotics.
The carnitine system is altered by several xenobiotics (drugs and chemicals). These alterations are responsible for most toxic effects, which can be reverted or minimized by L-carnitine administration. Formation of nonmetabolizable acyl coenzyme A (CoA) is a typical step in the biotransformation of pivaloyl antibiotics, valproate and ifosfamide. The elevated levels of acylcarnitine occurring in human urine due to impaired metabolism of specific acyl CoA support the role of L-carnitine as an acceptor of specific, nonmetabolizable acyl CoA. The consequence of this process is a secondary carnitine deficiency. The formation of stable complexes with an essential component of mitochondrial membrane, cardiolipin, and the inhibition of myocardial specific isoform of carnitine-palmitoyl transferase are presumably the basis of adriamycin cardiotoxicity. L-carnitine interacts with cardiolipin, modifying membrane permeability and protecting the functions of the mitochondria. This mechanism can be proposed to explain the protective effects of L-carnitine against adriamycin cardiotoxicity, ammonium acetate and zidovudine-induced mitochondrial ultrastructural and functional alterations. Cisplatin, cephalosporin and carbapenem antibiotics inhibit carnitine reabsorption in renal tubules and cause proximal tubular damage. The study of peroxisomal producing agents belonging to largely different chemical classes showed that these agents caused carnitine system perturbations which may have the potential to be highly relevant biomarkers of exposure to the nongenotoxic peroxisomal proliferating agent class of hepatic tumorigens.
Arrigoni-Martelli
E
E
Caso
V
V
D000214:Acyl Coenzyme A / Q000378:metabolism; D000641:Ammonia / Q000009:adverse effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D019380:Anti-HIV Agents / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D001427:Bacterial Toxins / Q000009:adverse effects; D002331:Carnitine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010421:Pentanoic Acids / Q000009:adverse effects; D020025:Peroxisome Proliferators / Q000009:adverse effects; D014635:Valproic Acid / Q000009:adverse effects; D015262:Xenobiotics / Q000009:adverse effects*
D000214:Acyl Coenzyme A; D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D010421:Pentanoic Acids; D020025:Peroxisome Proliferators; D015262:Xenobiotics; D014635:Valproic Acid; D000641:Ammonia; C005566:pivalic acid; D002331:Carnitine