Effect of Ethanolic extract of Boerhvia diffusa against doxorubicin induced Nephrotoxicity in Albino Rats

S. K. Nimbal, B. Koti
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Abstract

Anthracycline derivative i.e. doxorubicin (Dox) has proven efficacy in several malignancies such as breast cancer, Hodgkin and non-Hodgkin lymphoma, acute leukemia, lung, thyroid and ovarian cancer. The clinical usefulness is restricted due to its cardiotoxicity and nephrotoxicity. Boerhaavia diffusa belongs to family Nyctaginaceae and in Ayurveda, it is claimed for use in renal disorders. The main phytoconstituents of the plant are alkaloids, terpenoids, tannins, glycosides, flavonoids, phenolic compounds. To investigate the ameliorative role of ethanolic extract of petals of B. diffusa in doxorubicin-induced nephrotoxicity in rats. Nephrotoxicity was produced by administering doxorubicin (2.5 mg/kg b.w., i.p. alternate day) in six equal injections for two weeks to become cumulatively 15 mg/kg. Low (LEBD–100 mg/kg p.o.) and high (HEBD–200 mg/kg p.o.) dose of ethanolic extract of Boerhhvia diffusa was administered as a pretreatment before doxorubicin administration. The general parameters such as body weight, food, and water intake were measured throughout the study period. Serum markers such as blood urea nitrogen (BUN), serum creatinine and albumin were measured. Antioxidant enzymes such as glutathione (GSH), malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) were monitored after the last dose. Histopathological studies were also carried out to evaluate nephrotoxicity. The repeated administration of doxorubicin produces several morphological changes, decreased body weight, food, and water consumption. Serum markers such as BUN and serum creatinine were increased and albumin levels decreased. The GSH, SOD, and CAT were decreased, whereas the MDA level was increased, and deteriorating changes in the histological architecture of kidney tissue were observed. The HEBD pretreated groups dosedependently increased body weight and food and water intake (p is less than  0.01 and p is less than 0.05), whereas LEBD does not show any significant changes. The LEBD and HEBD pretreated groups decreased the BUN (p is less than 0.05 and p is less than 0.01) and serum creatinine (p is less than 0.05 and p is less than 0.05) and increased in the albumin (p is less than 0.05 and p is less than 0.05) levels, respectively. The pretreatment with LEBD and HEBD increased the level of the antioxidant enzyme i.e., GSH (p is less than 0.05 and p is less than 0.01), SOD (p is less than 0.05 and p is less than 0.01), CAT (p is less than 0.05 and p is less than 0.01) and decreased the MDA level (p is less than 0.05 and p is less than 0.01) respectively. Histopathological studies showed that the pretreatment with LEBD and HEBD groups minimized the tubular damage and reduced the inflammation as compared to doxorubicin-treated group. The biochemical and histopathological results data support the nephroprotective effect of ethanolic extract of B. diffusa, which might be credited to its antioxidant property.
白花菊醇提物对阿霉素致白化大鼠肾毒性的影响
蒽环类衍生物,即阿霉素(Dox)已被证明对几种恶性肿瘤有效,如乳腺癌、霍奇金淋巴瘤和非霍奇金淋巴瘤、急性白血病、肺癌、甲状腺癌和卵巢癌。由于其心脏毒性和肾毒性,其临床应用受到限制。Boerhaaviadiffusa属于Nyctaginaceae家族,在阿育吠陀中,它被声称用于肾脏疾病。该植物的主要成分有生物碱、萜类、单宁、苷类、黄酮类、酚类化合物等。探讨白花花花瓣乙醇提取物对阿霉素所致大鼠肾毒性的改善作用。给予阿霉素(2.5 mg/kg体重,隔天1次,每次1次)6次等量注射,连续2周达到累计15 mg/kg,产生肾毒性。低剂量(LEBD-100 mg/kg p.o)和高剂量(HEBD-200 mg/kg p.o)白花菊乙醇提取物作为阿霉素给药前的预处理。在整个研究期间测量了一般参数,如体重、食物和水的摄入量。测定血清指标如尿素氮(BUN)、血清肌酐、白蛋白。最后一次给药后监测抗氧化酶如谷胱甘肽(GSH)、丙二醛(MDA)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)。还进行了组织病理学研究以评估肾毒性。反复给予阿霉素可产生多种形态学改变,体重、食物和水的消耗减少。血清指标如BUN和肌酐升高,白蛋白水平降低。GSH、SOD、CAT水平降低,MDA水平升高,肾组织组织结构发生恶化变化。HEBD预处理组大鼠体重和摄食量呈剂量依赖性增加(p < 0.01和p < 0.05), LEBD预处理组大鼠无显著变化。LEBD和HEBD预处理组分别降低了BUN (p < 0.05和p < 0.01)和血清肌酐(p < 0.05和p < 0.05),升高了白蛋白(p < 0.05和p < 0.05)水平。LEBD和HEBD预处理分别提高了抗氧化酶GSH (p < 0.05和p < 0.01)、SOD (p < 0.05和p < 0.01)、CAT (p < 0.05和p < 0.01)和MDA (p < 0.05和p < 0.01)水平。组织病理学研究表明,与阿霉素治疗组相比,LEBD和HEBD预处理组使小管损伤最小化,炎症减轻。生物化学和组织病理学结果支持白花草乙醇提取物的肾保护作用,这可能与白花草乙醇提取物的抗氧化作用有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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