Protective effect of L-carnitine versus amifostine against cisplatin-induced nephrotoxicity in rats.

Department of Medical Oncology, Faculty of Medicine, Trakya University, Edirne, Turkey.
Medical Oncology (Impact Factor: 2.14). 12/2010; 28 Suppl 1:S690-6. DOI: 10.1007/s12032-010-9746-2
Source: PubMed

ABSTRACT We aimed to compare the protective effect of L-carnitine (CAR) and amifostine (AMF) against cisplatin (CDDP)-induced nephrotoxicity through biochemical markers and histopathological evaluation. Fifty-seven Wistar albino male rats were randomly classified into six groups, which were AMF+CDDP (n = 11; 200 mg/kg AMF 30 min prior to 7 mg/kg CDDP), CAR+CDDP (n = 11; 300 mg/kg CAR 30 min prior to 7 mg/kg CDDP), CDDP (n = 11; 1 mL/kg isotonic saline 30 min prior to 7 mg/kg CDDP), AMF (n = 8; 200 mg/kg AMF alone), CAR (n = 8; 300 mg/kg CAR alone), and control (n = 8; 1 mL/kg isotonic saline alone). All drugs were given intraperitoneally. Five days after medication, animals were killed, and samples of blood and kidney tissues were collected for biochemical and histopathological evaluation. The serum urea level was highest in AMF+CDDP group among CDDP-applied groups without statistical significance (median, range: 88, 56-21 mg/dL; P > 0.05). There was no statistical significance among CDDP-applied groups in terms of creatinine level (P > 0.05). In the AMF+CDDP group, the median glomerular, tubular, and tubulointerstitial inflammatory damage scores were significantly higher than the other CDDP-applied groups (P < 0.001). The difference between CAR+CDDP and CDDP groups was not statistically significant in terms of renal damage scores. AMF+CDDP group had significantly higher median total nephrotoxicity score than all the other groups (P < 0.001). To conclude, AMF or CAR has no protective effect on CDDP-induced nephrotoxicity. Furthermore, our findings suggest that application of AMF before CDDP may enhance CDDP-induced nephrotoxicity histopathologically.

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    ABSTRACT: Background: Ablative radioiodine-131 ((131)I) therapy is used in the standart treatment procedure of thyroid carcinoma and procedures using (131)I represent the majority of Nuclear Medicine therapeutic procedures. The principal route of (131)I excretion after the administration of (131)I is the urine. Amifostine is an organic thiophosphate ester prodrug and the kidney concentrations of the active metabolite WR-1065 are about 100 times higher than tumour concentrations. To our knowledge, there is no published data in literature presenting acute effect of radioiodine on renal tissue during high dose I-131 radioiodine treatment (RIT). Additionally, it is not known whether amifostine takes role in this process. Materials and Methods: In this study, 50 healthy female Wistar albino rats, weighing 200-250 g and averaging 16 weeks old were utilised. The rats were randomly divided into ten groups. 1- Sham group (n=5), 2- Amifostine group (n=5): rats pretreated with 1 cc amifostine (200 mg/kg) by intraperitoneal injection, 3- Radioactive iodine first day group (RI-1) (n=5): rats treated with 1 cc oral 185 MBq radioactive iodine-131 and sacrification performed after 1(st) day, 4- Amifostine + Radioactive iodine first day group (A+RI-1) (n=5): rats pretreated with amifostine (200 mg/kg) by intraperitoneal injection and rats treated with 5mCi radioactive iodine-131 and sacrification performed after 1(st) day. 5- Radioactive iodine third day group (RI-3) (n=5), 6- Amifostine + Radioactive iodine third day group (A+RI-3) (n=5), 7- Radioactive iodine fifth day group (RI-5) (n=5), 8- Amifostine + Radioactive iodine fifth day group (A+RI-5) (n=5), 9- Radioactive iodine seventh day group (RI-7) (n=5) and 10- Amifostine + Radioactive iodine seventh day group (A+RI-7) (n=5). The renal cast formation and tubular damage are evaluated by a pathologist in a blinded manner. Results: Ablative radioiodine-131 therapy induced renal tubular damage was significantly higher in the radioactive iodine fifth day group (RI-5) when compared with the Sham group (p=0.01) and Amifostine group (p=0.01). Conclusions: A marked ablative radioiodine-131 induced renal toxicity was seen at fifth day of the therapy after a single RIT application and the main histopathological change was tubular damage. Amifostine have protective effects against ablative radioiodine-131 therapy and this effect is significant at fifth day of the therapy.
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    ABSTRACT: Introduction: Drug-induced nephrotoxicity (DIN) has been reported with a great number of medications and contributes to ∼ 20% of hospital admissions. l-carnitine owing to its antioxidant, anti-inflammatory and antiapoptotic properties has been proposed as a candidate for nephroprotection against DIN. Increasing need to use nephrotoxic therapeutic agents necessitated this review. Areas covered: The present review covers all published clinical and animal researches on nephroprotective effects of l-carnitine against 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. Expert opinion: In spite of the evidences that support the nephroprotective effect of l-carnitine, the main problems in this area are inadequacy of reliable studies in humans and difficulty of translating the experimental results into clinical practice. In most of the described studies, l-carnitine treatment is prophylactically given. Use of l-carnitine as a prophylactic agent in clinical situations with an indication for nephrotoxic therapies is rarely possible except for contrast-induced nephrotoxicity. Development of validated early biomarkers to detect DIN may provide the opportunity to use prophylactic nephroprotective agents at golden time.
    Expert Opinion on Drug Safety 05/2013; · 2.74 Impact Factor
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