L-Carnitine Protective Effect in Nephrotoxicity

Cisplatin is one of the most effective chemotherapeutic agents that has been used for more than 50 years for a different solid Tumers. Nevertheless, its administration is associated with toxicity, including nephrotoxicity which can affects 25-35% of treated patients. Cisplatin nephrotoxicity mainly explained by accumulation in the renal tubules mostly in the proximal and distal tubules where it inhibits and alters the expression pattern of several membrane transporters and water channels and inhibits mitochondrial function and ATP production, thus generating oxidative stress. Cisplatin nephrotoxicity is also associated with an inflammatory response that plays a significant role in this event. Tumor necrosis factor alpha (TNF- α) is a pleiotropic pro-inflammatory cytokine that signals via TNFRSF1A and TNFRSF1B to activate nuclear factor kappa B (NF-κB) or Mitogen-activated protein kinase (MAPK), eventually leading to cytokine production and/or death signaling. L-carnitine owing to its antioxidant and anti-inflammatory properties has been used as a candidate for nephroprotection against drug induced nephrotoxicity (DIN). L-carnitine significantly ameliorates DIN in animal studies especially against cisplatin-induced renal damage. Inhibition of reactive oxygen species generation, lipid peroxidation, matrix remodeling and apoptosis, anti-inflammatory properties and improvement in carnitine deficiency has been suggested as probable nephroprotective mechanisms of L-carnitine.

Inclusion criteria

• Male or female patients.
• Newly diagnosed patients with cancer and with an indication for cisplatin - based chemotherapy.
• Age between 18 and 75 years.
• No serious cardiopulmonary comorbidity which could impair involvement in the study.
• Creatinine clearance value above 50 mL/min/1.73 m².
• Patients who will scheduled to receive at least 3 cycles of cisplatin.
• Patients with no previous renal diseases (including acute nephropathy, acute and chronic renal failure).

Exclusion criteria

• Pregnancy or lactation.
• Metastasis to the central nervous system.
• Psychiatric disorders.
• Prior treatment with platinum derivatives.
• Hypersensitivity to cisplatin, carboplatin or other platinum derivatives.
• Patients with active infection or any symptoms of sepsis.
• Acute renal failure or renal surgery within the last 3 months.
• Patients unfit for cisplatin (patients with impaired renal function, sensorineural hearing loss and cardiomyopathy).
• Patients with known history or current treatment with nephrotoxic agents.
• Taking other antioxidant supplements such as Vitamins C and E.