Comparison of protective effects of L-carnitine and amifostine on radiation-induced toxicity to growing bone: histopathology and scintigraphy findings.

PURPOSE: The aim of the present study was to evaluate the radioprotective efficacy of L-carnitine (LC) in growing bones in comparison to amifostine. MATERIALS AND METHODS: Sixty two-week-old Wistar albino rats were randomly assigned to six equal groups: Group 1, control (CONT); Group 2, irradiation alone (RT); Group 3, amifostine plus irradiation (AMI+ RT); Group 4, L-carnitine plus irradiation (LC+ RT); Group 5, amifostine alone (AMI); Group 6, L-carnitine alone (LC). The rats in the AMI+ RT, LC+ RT and RT groups were irradiated individually with a single dose of 20 Gy to the left femur. LC (300 mg/kg) and amifostine (200 mg/kg) were applied 30 min before irradiation. The animals were scanned for bone area, mineral content and bone mineral density (BMD) by DEXA and the 99mTc methylene diphosphonate uptake ratio (MUR) was calculated by bone scintigraphy. Histopathological analysis of bone and cartilage was also carried out after euthanasia. RESULTS: Pretreatment with LC or amifostine reduced the radiation-induced damage in growing bone (p= 0.007 and p= 0.04 respectively) and in the epiphysial cartilage (p= 0.002 and p= 0.015 respectively). The protective effect of LC was similar to that of amifostine on both growing bone and on the epiphysial cartilage. The mean left-femur BMD values were significantly higher in the LC+RT (p= 0.02) and AMI+RT (p= 0.01) groups than in the RT group. but did not differ with the two protective agents. Pretreatment with AMI (p= 0.002) and LC (p= 0.01) improved the MUR. CONCLUSIONS: L-carnitine is equally as effective as amifostine at protecting growing bone against single dose irradiation damage.

Histopathological and scintigraphic comparisons of the protective effects of L-carnitine and amifostine against radiation-induced late renal toxicity in rats.

1. The aim of the present study was to compare the protective effects of L-carnitine and amifostine against radiation-induced late nephrotoxicity using technetium-99m diethylenetriaminepentaacetic acid scintigraphy and histopathological examination. 2. Seventy-one Albino rats were randomly divided into six groups as follows: (i) AMI + RAD (n = 15), 200 mg/kg, i.p., amifostine 30 min prior to irradiation (a single dose of 9 Gy); (ii) LC + RAD (n = 15), 300 mg/kg, i.p., L-carnitine 30 min prior to irradiation; (iii) LC (n = 10), 300 mg/kg, i.p., L-carnitine 30 min prior to sham irradiation; (iv) AMI (n = 10), 200 mg/kg, i.p., amifostine 30 min prior to sham irradiation; RAD (n = 11), 1 mL/kg, i.p., normal saline 30 min prior to irradiation; and (vi) control (n = 10), 1 mL/kg, i.p., normal saline 30 min prior to sham irradiation. Scintigraphy was performed before treatment and again 6 months after treatment. Kidneys were examined by light microscopy and a histopathological scoring system was used to assess the degree of renal damage. 3. The main histopathological findings were proximal tubular damage and interstitial fibrosis. Glomerular injury was similar in all groups. Tubular degeneration and atrophy were less common in the AMI + RAD group than in the RAD group (P = 0.011 and P = 0.015, respectively), as well as in the LC + RAD group compared with the RAD group (P = 0.028 and P = 0.036, respectively). Interstitial fibrosis in the AMI + RAD and LC + RAD groups was significantly less than that in the RAD group (P = 0.015 and P = 0.015, respectively). The highest total renal injury score (9) was seen in the RAD group. On scintigraphy, there were significant differences in post-treatment time to peak count (T(max)) and time from peak count to half count (T((1/2))) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T((1/2)) of the right kidney was 8 +/- 2 and 21 +/- 2 min, respectively. The T(max) values for the AMI + RAD and LC + RAD groups (2.8 +/- 0.2 and 3.2 +/- 0.2 min, respectively) were similar to those in the control group (2.5 +/- 0.3 min). 4. Based on the results of the present study, L-carnitine and amifostine have comparable and significant protective effects against radiation-induced late nephrotoxicity.