Evaluation of the Effect of Acetyl <i>L</i>-Carnitine on Experimental Cisplatin Nephrotoxicity

Abstract

Background/Aims: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity. Methods: Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically. Results: In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3. Conclusions: Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.

The Protective Effects of Acetyl L-Carnitine on Testis Gonadotoxicity Induced by Cisplatin in Rats

“…Saline was simultaneously injected s.c. at the same dose in Groups 1 and 3. Cisplatin (Cisplatin-Ebewe ® 13 mg/kg body weight, Liba, Istanbul, Turkey) was administered 30 min after acetyl L-carnitine/saline injection via intraperitoneal infusion for 1hr only on the first day in Groups 3 and 4 (15,16).…”

“…However, the powerful anti-tumoural activity of cisplatin also stops the growth and proliferation of cancer cells. Common adverse effects, such as gonadotoxicity, nephrotoxicity, ototoxicity and neurotoxicity, have been reported as dose-limiting adverse effects (5,15,16). After entering a tumour cell, cisplatin activates many signalling pathways to cause apoptosis, necrosis, oxidative stress, fibrogenesis, inflammation, hypoxia and mitochondrial damage, and it also induces cytotoxic effects in healthy cells (7,10,(21)(22)(23).…”

“…Acetyl L-carnitine has been shown to protect cells against mitochondrial and free radical-related nuclear DNA damage and to improve mitochondrial functions by reducing stress-mediated DNA damage through reducing the production of oxidants and enhancing antioxidant status (13,(14)(15)(16)(17). Many studies have demonstrated that free carnitine levels in the epididymis affect the number, motility and maturity of spermatozoa (18,19).…”

“…The potent anti-apoptotic ability of acetyl L-carnitine to prevent oxidative stress-related mitochondrial damage and subsequent mitochondria-dependent apoptosis has been demonstrated in many cell types (14)(15)(16)(17). The high concentration of acetyl L-carnitine that is present in testicular tissues leads to an increase in mitochondrial fatty acid oxidation, which is used to produce energy for sperm respiration and motility (18)(19)(20).…”

Metabolic Approach to the Enhancement of Antitumor Effect of Chemotherapy: a Key Role of Acetyl-l-Carnitine

“…Moreover, we have shown for the first time that ALC may have antimetastatic activity in a lung carcinoma model. Both effects, likely related to modulation of protein acetylation, may have obvious therapeutic implications, also taking into account the excellent in vivo tolerability of ALC and its protective action against cisplatin-induced nephrotoxicity (32) or peripheral neuropathy (33). 50 and P values (F-test) were calculated by the ALLFIT program.…”