الفهرس 
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Abstract
The present study is conducted to investigate the effect of CoQ10 on Dox-induced nephrotoxicity in rats. Our study is the first that proves the protective effect of CoQ10 against Dox-induced renal damage. Male albino rats were divided into 6 main groups; untreated (control), animals treated with CoQ10 (10 mg/kg/day) (CoQ10L), CoQ10 (100 mg/kg/day) (CoQ10H), Dox-treated (Dox), concomitant Dox with CoQ10L-treated (Dox/CoQ10L) and concomitant Dox with CoQ10H-treated (Dox/CoQ10H) groups. Administration of CoQ10 was started 3 days before Dox administration and continued for 5 days.
Results showed that kidney/body weight ratios in CoQ10L and CoQ10H groups did not significantly differ from that of control. On the other hand, kidney/body weight ratios in Dox group significantly increased compared to control group. Concomitant administration of CoQ10L and CoQ10H did not statistically decrease in kidney/body weight ratio.
At sacrifice death rate of each animal group was detected. death rate of control, CoQ10L and CoQ10H groups were all 0%. On the other hand, death rates in Dox, Dox/CoQ10L and Dox/CoQ10H groups were 40, 25 and 8.3%, respectively, implying CoQ10 dose-dependent decreased rate of death of rats in these groups.
Administration of single dose of Dox (15 mg/kg, i.p) caused significant deterioration in renal function, designated by the increase in both serum creatinine and BUN concentrations. Co-administration of either low or high doses of CoQ10 with Dox resulted in decreasing in serum creatinine and BUN. However, CoQ10H did not show more improvement than CoQ10L.
In renal tissue samples of Dox group, Dox caused oxidative stress, as evident by the significant decrease in renal GSH and catalase. Treatment with CoQ10L significantly reversed the oxidative effect of Dox on renal GSH and catalase but CoQ10H increased GSH but did not improve catalase level. Interestingly, CoQ10H without Dox resulted in oxidative stress effect, represented by significant decrease in renal GSH and catalase compared to control group. Dox also significantly increased renal MDA compared to control, which was reversed by both low and high doses of CoQ10.
Doxorubicin also significantly increased renal nitric oxide compared to control. CoQ10H, but not CoQ10L, succeeded in reversing this increase to levels comparable to that of control. CoQ10 alone in a low or high dose had no significant effect on renal nitric oxide levels.
Histopathological examination showed marked renal damage in Dox-treated group, which reversed by concomitant administration of CoQ10L. CoQ10H did not show similar effect. Furthermore, sole administration of CoQ10H showed some histopathological renal damage. A similar picture was seen in studying the immunohistochemical changes with semiquantitative analysis of caspase 3 as a marker of apoptosis, where Dox induced the expression of caspase 3, CoQ10L reversed this effect, but CoQ10H did not achieve similar effect. In addition, CoQ10H alone without Dox treatment showed mild induction of caspase 3.
from these data, it is clear that CoQ10 was able to attenuate nephrotoxicity induced by Dox mainly through its anti-oxidant properties. Increasing the dose of CoQ10 showed no benefits over low dosage.