بررسی اثر پروفیلاکسی و درمانی ال- آرژنین در پیش‌گیری از نفروتوکسیسیتی ناشی از سیس‌پلاتین در رت: نقش تفاوت جنسیت

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 دانشجوی پزشکی، مرکز تحقیقات آب و الکترولیت و دانشکده‌ی پزشکی و کمیته‌ی تحقیقات دانشجویی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

2 دانشیار، مرکز تحقیقات آب و الکترولیت و گروه آسیب شناسی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

3 استاد، مرکز تحقیقات آب و الکترولیت و گروه فیزیولوژی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان و موسسه‌ی تحقیقاتی اصفهان، اصفهان، ایران

چکیده

مقدمه: نفروتوکسیسیتی از عوارض مهم درمان با سیس‌پلاتین است که ناشی از ایجاد استرس اکسیداتیو می‌باشد. نفروتوکسیسیتی ناشی از سیس‌پلاتین از یک طرف وابسته به جنس است و از طرفی، عامل اصلی برای محدود نمودن درمان با سیس‌پلاتین می‌باشد. از این رو، استفاده از مکمل‌ها برای پیش‌گیری و یا کاهش نفروتوکسیسیتی ناشی از سیس‌پلاتین ضروری است. این مطالعه، با هدف بررسی اثر پروفیلاکسی و درمانی ال- آرژنین در نفروتوکسیسیتی ناشی از سیس‌پلاتین در رت‌های نر و ماده طراحی گردید.روش‌ها: 16 سر رت نر و 20 سر رت ماده از نژاد ویستار به طور تصادفی در 8 گروه قرار گرفتند. گروه‌های 1 و 5 به عنوان گروه‌های شاهد مثبت نر و ماده، سیس‌پلاتین را با دوز روزانه 5/2 میلی‌گرم به ازای هر کیلوگرم وزن بدن به مدت یک هفته دریافت نمودند. گروه‌های 2 و 6 به عنوان گروه‌های پروفیلاکسی نر و ماده، ال- آرژنین را با دوز روزانه‌ 150 میلی‌گرم به ازای هر کیلوگرم وزن بدن به مدت سه روز دریافت کردند و سپس از روز سوم، سیس‌پلاتین به مدت یک هفته تجویز شد. گروه‌های 3 و 7 به عنوان گروه‌های پروفیلاکسی همراه با درمان تحت دریافت ال- آرژنین به مدت سه روز قرار گرفتند و سپس بدون این که تزریق روزانه‌‌ی ال- آرژنین قطع شود، از روز سوم سیس‌پلاتین به مدت یک هفته تزریق شد.گروه‌های 4 و 8 به عنوان گروه‌های درمان دریافت روزانه و هم‌زمان سیس‌پلاتین و ال- آرژنین را داشتند. در روز دهم، خون‌گیری انجام شد و کلیه‌ها جهت فرایند بافت‌شناسی آماده گردیدند.یافته‌ها: هیچ یک از روش‌های تجویز ال- آرژنین در جنس ماده تفاوتی را با گروه شاهد مثبت ایجاد نکرد. اما همرا ه شدن ال- آرژنین با سیس‌پلاتین بدون پروفیلاکسی در جنس نر (گروه 4) موجب کاهش معنی‌دار سطح سرمی ازت اوره‌ی خون و کراتینین و شدت آسیب بافت کلیوی گردید (05/0 > P). وزن کلیه، همچنین در گروه 4 نسبت به گروه شاهد کاهش داشت؛ هر چند معنی‌دار نبود (20/0 = P) که نشانگر کاهش شدت آسیب است. تفاوت معنی‌داری در سطح بافتی نیتریت در بین گروه‌های نر دیده نشد، اما کاهش وزن در بین این گروه‌ها متفاوت بود و گروه‌های دریافت کننده‌ی ال- آرژنین کاهش وزن بیشتری را نسبت به گروه شاهد مثبت نشان دادند (05/0 > P).نتیجه‌گیری: تجویز ال- آرژنین به عنوان پیش‌ساز نیتریک اکسید، هم‌زمان با سیس‌پلاتین می‌تواند موجب کاهش نفروتوکسیسیتی ناشی از سیس‌پلاتین در جنس نر باشد که احتمال می‌رود از طریق اصلاح عملکرد آندوتلیوم که به وسیله‌ی سیس‌پلاتین مختل شده است، می‌باشد.

کلیدواژه‌ها

عنوان مقاله [English]

The Evaluation of L-arginine Prophylaxis and Treatment on Preventing Nephrotoxicity Cisplatin-Induced in Rat: Role of Gender Difference

نویسندگان [English]

  • Moazzameh Meimandinia 1
  • Roya Amiri 1
  • Fatemeh Eshraghi-Jazi 1
  • Ardeshir Talebi 2
  • Mehdi Nematbakhsh 3
1 Student of Medicine, Water and Electrolytes Research Center AND School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
2 Associate Professor, Water and Electrolytes Research Center AND Department of Clinical Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Professor, Water and Electrolytes Research Center AND Department of Physiology, School of Medicine, Isfahan University of Medical Sciences AND Institute of Basic and Applied Sciences Research, Isfahan, Iran
چکیده [English]

Background: Nephrotoxicity is the main side effect of cisplatin (CP)-therapy which is induced by oxidative stress. Nephrotoxicity is gender related and limits the cisplatin treatment. Therefore, it is essential to prevent or to ameliorate cisplatin-induced nephrotoxicity via administration of supplementations. This study was designed to investigate the effect of L-arginine (L-Arg) prophylaxis and treatment on preventing cisplatin-induced nephrotoxicity in male and female rats.Methods: Sixteen male and twenty female Wistar rats were divided into eight groups. Groups 1 (male) and 5(female), as positive control groups, received cisplatin (2.5 mg/kg/day; Intraperitoneally) for a week. Groups 2 (male) and 6 (female) received L-arginine (150 mg/kg/day; Intraperitoneally) as prophylaxis for 3 days, and cisplatin was administered from the day 3 for a week. Groups 3 (male) and 7 (female) received L-arginine, as prophylaxis for 3 days; and cisplatin was administered from the day 3, for a week, without withdrawal of daily L-arginine administration. Groups 4 (male) and 8 (female) received cisplatin and L-arginine simultaneously for a week. On the day 10, blood samples were taken and kidneys were prepared for histopathological investigation.Findings: L-arginine administration did not changed the measured parameters from positive control group in females. Simultaneous administration of cisplatin and L-arginine decreased serum levels of blood urea nitrogen and creatinine as well as intensity of renal tissue damage in comparison with positive control group in males (P < 0.05). In addition, it ameliorated kidney weight in comparison with positive control group in male, insignificantly (P = 0.20). No significant difference was observed in tissue nitrite level among male groups and L-arginine treated male groups had body weight loss more than positive control group (P < 0.05).Conclusion: Simultaneous administration of L-arginine, as nitric oxide precursor, and cisplatin could ameliorate cisplatin-induced nephrotoxicity in male gender through improving endothelium function.

کلیدواژه‌ها [English]

  • Cisplatin
  • Nephrotoxicity
  • L-arginine
  • Gender

مراجع

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مجله دانشکده پزشکی اصفهان
دوره 33، شماره 339 - شماره پیاپی 339
مرداد و شهریور 1394
صفحه 932-944

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  • تاریخ دریافت: 12 دی 1393
  • تاریخ بازنگری: 11 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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