HISTOPATHOLOGICAL AND SCINTIGRAPHIC COMPARISONS OF THE PROTECTIVE EFFECTS OF l‐CARNITINE AND AMIFOSTINE AGAINST RADIATION‐INDUCED LATE RENAL TOXICITY IN RATS

Abstract

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.

Experimental Quantification of Delayed Radiation-Induced Organ Damage in Highly Irradiated Rats With Bone Marrow Protection

“…4b, Table 2). Similar glomerular lesions have been described previously (Sieber et al 2009;Caloglu et al 2009). Kidney lesions were obvious in the cortex 64 d post-irradiation, but analysis revealed that deeper lesions developed between 64 and 104 d after irradiation, as shown by the increased histological score in the medulla between 64 and 104 d post-irradiation (Table 2).…”

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

“…Its protective effect in CDDP-induced renal and intestinal toxicity [11], gentamicin-induced nephrotoxicity [12], doxorubicin-induced nephrotoxicity [13], and chronic renal failure [14] has been demonstrated by various models. Although it has been recently reported that CAR and AMF have comparable and significant protective effects against radiation-induced nephrotoxicity in rats [15], their comparative effects against CDDP-induced nephrotoxicity have not been studied before.…”

L-carnitine has a protective effect on the colonic mucosa during abdominopelvic radiotherapy in rats

“…Intraperitoneal injections were made by dividing the abdomen into four quadrants on an imaginary midline and one perpendicular line at the level of the umbilical mark, L-carnitine and sterile saline were administered into the lower-left quadrant by using 1-ml syringes with a 26 G 3/8-inch needles. The selection of the 30-min interval between intraperitoneal L-carnitine administration and exposure to radiation was based on a previous experimental study 14 .…”

“…The body can endogenously synthesize about 10% of the L-carnitine it requires from lysine and methionine amino acids in the skeletal muscle, heart, liver, kidney, and brain; the remaining amount is generally obtained through diet 12,13 . Experimental models have demonstrated its radioprotective effects in the kidney, lens and cochlea, retina, brain, growing bone, testes, oral mucosa, small intestine and bone marrow [14][15][16][17][18][19][20][21] .…”