عه اثرات محافظتی رزوراترول (Resveratrol) بر سمیّت کبدی داروی شیمی‌درمانی سیسپلاتین در موش صحرایی

محورهای موضوعی : آسیب شناسی درمانگاهی دامپزشکی

رامین کفاشی‌الهی ¹

1 - دانشگاه آزاد اسلامی، واحد تبریز، دانشکده دامپزشکی، استادیار گروه آموزشی علوم درمانگاهی، تبریز، ایران.

تاریخ دریافت : 1392/09/12 تاریخ پذیرش : 1393/04/03 تاریخ انتشار : 1392/12/01

کلید واژه: موش صحرایی, رزوراترول, سیسپلاتین, سمیت کبدی,

چکیده مقاله :

دارو درمانی سرطان که با استفاده از مواد طبیعی، صناعی یا بیولوژیک انجام می شود، با عوارضی همراه است. سیسپلاتین به عنوان یک داروی ضدسرطان، در دوزهای بالا برای کبد سمّی است. معلوم شده که استرس اکسیداتیو در سمّیت سیسپلاتین دخیل است. با توجه به اثرات آنتی اکسیدانی رزوراترول، این مطالعه، برای ارزیابی اثرات محافظتی آن در برابر سمیّت کبدی سیسپلاتین در موش صحرایی انجام شد. 40 سر موش صحرایی نر ویستار به طور تصادفی در چهار گروه مساوی تقسیم گردید. گروه 1 به عنوان شاهد انتخاب شد. برای ایجاد آسیب کبدی، سیسپلاتین (mg/kg 3) هر 5 روز یکبار به‌صورت داخل صفاقی به گروه‌های 2 تا 4 تزریق شد. گروه 3 سیلیمارین (mg/kg 100) و گروه‌ 4 رزوراترول (mg/kg 20) را با تزریق داخل صفاقی روزانه به‌مدت 4 هفته دریافت کردند. در پایان، سطوح سرمی آنزیم‌های آسپارتات و آلانین آمینوترانسفراز و لاکتات دهیدروژناز و بیلی‌روبین تام، آلبومین و پروتئین تام اندازه گیری شد. میزان مالون دی آلدئید، گلوتاتیون احیاء و فعالیت آنزیم های سوپراکسید دیسموتاز، کاتالاز، گلوتاتیون پراکسیداز و گلوتاتیون ردوکتاز نیز در هموژنات بافت کبد اندازه گیری شد. در نهایت، یافته های بیوشیمیایی با نتایج هیستوپاتولوژی مطابقت داده شد. در گروه 4، رزوراترول به‌طور معنی‌داری (001/0p<) میزان افزایش یافته آنزیم‌های شاخص آسیب کبد و بیلی‌روبین تام را کاهش و سطوح کاهش یافته آلبومین و پروتئین تام سرم را به‌طور معنی‌داری (001/0p<) افزایش داد. رزوراترول در این گروه، به طور معنی‌داری (001/0p<) میزان پراکسیداسیون لیپیدی را کاهش و سطوح آنتی اکسیدان های کبد را افزایش داد. از لحاظ آسیب شناسی بافتی نیز تغییرات با یافته های بیوشیمیایی همراستا بودند. نتایج بررسی حاضر نشان داد که رزوراترول با خواص آنتی‌اکسیدانی خود، کبد موش های صحرایی را در برابر سمّیت سیسپلاتین محافظت می کند.

چکیده انگلیسی:

   Drug therapy of cancer which is carried out by natural, synthetic or biological substances is associated with complications. Cisplatin as an anticancer drug, is hepatotoxic at high doses. Oxidative stress has been proven to be involved in cisplatin-induced toxicity. Because of antioxidant potential of resveratrol, this study was conducted to assess the protective effects of resveratrol, on cisplatin-induced hepatotoxicity in the rat. Forty male Wistar rats were randomly divided into four equal groups. Group 1 was used as control. For induction of hepatic injury in groups 2-4, cisplatin (3 mg/kg) was injected once every five days intraperitoneally. Groups 3 and 4 received silymarin (100 mg/kg) and resveratrol (20 mg/kg) respectively, daily for 4 weeks via intraperitoneal route. At the end of experiment, serum levels of aspartate and alanine transaminases, lactate dehydogenase and total bilirubin, albumin and total proteins were assessed. Malondialdehyde, reduced glutathione and activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were assayed in liver homogenates. Finally, the biochemical findings were matched with histopathological verification. In group 4, resveratrol significantly (p<0.001) decreased the elevated levels of serum biomarkers of hepatic injury and total bilirubin, and significantly (p<0.001) increased the reduced levels of serum albumin and total proteins. In this group, resveratrol significantly (p<0.001) decreased the lipid peroxidation and elevated the decreased values of hepatic antioxidants. Histopathologically, the changes were in agreement with biochemical findings. The results obtained showed resveratrol, because of its anti-oxidant potential, exerts a protective effect against cisplatin induced hepatotoxicity in rats.

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