Sule Parlar

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 (Tmax) and time from peak count to half count (T½) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T½ of the right kidney was 8 ± 2 and 21 ± 2 min, respectively. The Tmax 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.

Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters.

Purpose:To assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis.Material and Methods:30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a 60Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated.Results:After irradiation, the median value of right kidney function was 48% (44–49%) and 50.5% (49%–52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%).Conclusion:Static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function.Ziel:Beurteilung der protektiven Wirkung von Amifostin auf die Nierenfunktion mittels semiquantitativer statischer szintigraphischer und histopathologischer Analyse.Material und Methodik:30 weibliche Albinoratten wurden in drei Gruppen mit jeweils zehn Tieren aufgeteilt: Kontrolle (CL), alleinige Radiotherapie (RT) und Radiotherapie + Amifostin (RT+AMI). Die Ratten in der CL- und RT-Gruppe erhielten eine Plazebosalzlösung, die Ratten in der RT+AMI-Gruppe 200 mg/kg Amifostin intraperitoneal 30 min vor der Bestrahlung. Die rechten Nieren in der RT- und RT+AMI-Gruppe wurden mit 6 Gy Einzeldosis mit einem 60Co-Gerät bestrahlt. Die Nachbeobachtungszeit betrug 6 Monate. Eine Nierenszintigraphie wurde direkt vor der Bestrahlung und vor Sektion bei den Tieren der RT- und RT+AMI-Gruppe durchgeführt. Der Nierenschaden wurde in der histopathologischen Untersuchung mit Tubulusatrophie und Fibrose qualitativ beurteilt.Ergebnisse:Die mediane Nierenfunktion der rechten Niere betrug in der RT- und RT+AMI-Gruppe 48% (44–49%) und 50,5% (49–52%; p = 0,0002). Grad-1-Fibrose lag in der RT-Gruppe bei 60% und in der RT+AMI-Gruppe bei 30%. Grad-2-Fibrose betrug in der RT-Gruppe 30% und in der RT+AMI-Gruppe 0%. Tubulusatrophie Grad 2 war in beiden Gruppen vergleichbar (10%).Schlussfolgerung:Die statische Nierenszintigraphie ist eine objektive, wiederholbare und nichtinvasive Methode zur Beurteilung der Nierenfunktion nach Bestrahlung. Im Tiermodell konnte Amifostin die strahleninduzierten Nierenschäden verringern.

Amifostine Use in Radiation-Induced Kidney Damage

Purpose:To assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis.Material and Methods:30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a 60Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated.Results:After irradiation, the median value of right kidney function was 48% (44–49%) and 50.5% (49%–52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%).Conclusion:Static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function.Ziel:Beurteilung der protektiven Wirkung von Amifostin auf die Nierenfunktion mittels semiquantitativer statischer szintigraphischer und histopathologischer Analyse.Material und Methodik:30 weibliche Albinoratten wurden in drei Gruppen mit jeweils zehn Tieren aufgeteilt: Kontrolle (CL), alleinige Radiotherapie (RT) und Radiotherapie + Amifostin (RT+AMI). Die Ratten in der CL- und RT-Gruppe erhielten eine Plazebosalzlösung, die Ratten in der RT+AMI-Gruppe 200 mg/kg Amifostin intraperitoneal 30 min vor der Bestrahlung. Die rechten Nieren in der RT- und RT+AMI-Gruppe wurden mit 6 Gy Einzeldosis mit einem 60Co-Gerät bestrahlt. Die Nachbeobachtungszeit betrug 6 Monate. Eine Nierenszintigraphie wurde direkt vor der Bestrahlung und vor Sektion bei den Tieren der RT- und RT+AMI-Gruppe durchgeführt. Der Nierenschaden wurde in der histopathologischen Untersuchung mit Tubulusatrophie und Fibrose qualitativ beurteilt.Ergebnisse:Die mediane Nierenfunktion der rechten Niere betrug in der RT- und RT+AMI-Gruppe 48% (44–49%) und 50,5% (49–52%; p = 0,0002). Grad-1-Fibrose lag in der RT-Gruppe bei 60% und in der RT+AMI-Gruppe bei 30%. Grad-2-Fibrose betrug in der RT-Gruppe 30% und in der RT+AMI-Gruppe 0%. Tubulusatrophie Grad 2 war in beiden Gruppen vergleichbar (10%).Schlussfolgerung:Die statische Nierenszintigraphie ist eine objektive, wiederholbare und nichtinvasive Methode zur Beurteilung der Nierenfunktion nach Bestrahlung. Im Tiermodell konnte Amifostin die strahleninduzierten Nierenschäden verringern.

RADIATION-INDUCED CHRONIC-OXIDATIVE RENAL DAMAGE CAN BE REDUCED BY AMIFOSTINE

In the current study, amifostine is evaluated for its radioprotective role in serum and kidney tissue by oxidative (malondialdehyde-MDA, advanced oxidation protein product-AOPP) and antioxidative markers (catalase, glutathione-GSH, free-thiols-F-SH). Thirty Wistar albino 3–4 months old, female rats, were randomly divided into Group I (n = 10): Control, Group II (n = 10): Irradiation-alone, Group III (n = 10): Amifostine before irradiation. In Group II and III, right kidneys of the rats were irradiated with a single dose of 6 Gy using a 60Co treatment unit. Rats in Group III received 200 mg/kg amifostine intraperitoneally, 30 min prior to irradiation. Following sacrification at 24th week, blood and kidney tissue samples were collected. Statistical analysis was done by One-way ANOVA, Post hoc Bonferroni, Dunnett T3, and Mann–Whitney U tests. Administration of amifostine significantly decreased the serum AOPP and MDA levels when compared to the irradiation-only group (P = 0.004, P = 0.006; respectively). Also amifostine significantly increased serum catalase activities and GSH levels, when given 30 min prior to irradiation (P = 00.02, P = 0.000; respectively). In the kidney tissue, administration of amifostine significantly decreased AOPP and MDA levels (P = 0.002, P = 0.016; respectively). Tissue GSH activity was increased following amifostine administration (P = 0.001). There was no statistically significant result on histopathological evaluation. Amifostine may reduce radiation-induced nephropathy by inhibiting chronic oxidative stress. Biomarkers of oxidative stress in serum and kidney tissue may be used for evaluation of the radiation-induced nephropathy.

Amifostine Use in Radiation-Induced Kidney Damage@@@Amifostin beim strahleninduzierten Nierenschaden. Effektivitätsbeurteilung mittels szintigraphischer und histopatologischer Parameter im Tiermodell: Preclinical Evaluation with Scintigraphic and Histopathologic Parameters

Purpose:To assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis.Material and Methods:30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a 60Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated.Results:After irradiation, the median value of right kidney function was 48% (44–49%) and 50.5% (49%–52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%).Conclusion:Static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function.Ziel:Beurteilung der protektiven Wirkung von Amifostin auf die Nierenfunktion mittels semiquantitativer statischer szintigraphischer und histopathologischer Analyse.Material und Methodik:30 weibliche Albinoratten wurden in drei Gruppen mit jeweils zehn Tieren aufgeteilt: Kontrolle (CL), alleinige Radiotherapie (RT) und Radiotherapie + Amifostin (RT+AMI). Die Ratten in der CL- und RT-Gruppe erhielten eine Plazebosalzlösung, die Ratten in der RT+AMI-Gruppe 200 mg/kg Amifostin intraperitoneal 30 min vor der Bestrahlung. Die rechten Nieren in der RT- und RT+AMI-Gruppe wurden mit 6 Gy Einzeldosis mit einem 60Co-Gerät bestrahlt. Die Nachbeobachtungszeit betrug 6 Monate. Eine Nierenszintigraphie wurde direkt vor der Bestrahlung und vor Sektion bei den Tieren der RT- und RT+AMI-Gruppe durchgeführt. Der Nierenschaden wurde in der histopathologischen Untersuchung mit Tubulusatrophie und Fibrose qualitativ beurteilt.Ergebnisse:Die mediane Nierenfunktion der rechten Niere betrug in der RT- und RT+AMI-Gruppe 48% (44–49%) und 50,5% (49–52%; p = 0,0002). Grad-1-Fibrose lag in der RT-Gruppe bei 60% und in der RT+AMI-Gruppe bei 30%. Grad-2-Fibrose betrug in der RT-Gruppe 30% und in der RT+AMI-Gruppe 0%. Tubulusatrophie Grad 2 war in beiden Gruppen vergleichbar (10%).Schlussfolgerung:Die statische Nierenszintigraphie ist eine objektive, wiederholbare und nichtinvasive Methode zur Beurteilung der Nierenfunktion nach Bestrahlung. Im Tiermodell konnte Amifostin die strahleninduzierten Nierenschäden verringern.