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百叶蔷薇乙醇提取物对白化大鼠阿霉素诱导的肾毒性的影响。

Effect of ethanolic extract of Rosa centifolia against doxorubicin induced nephrotoxicity in albino rats.

作者信息

Nimbal S K, Gadad Pramod C, Koti Basavaraj C

机构信息

Dept. of Pharmacology, KLE College of Pharmacy, Vidyanagar, Hubballi-31, (A constituent unit of KLE Academy of Higher Education and Research, Belagavi) Karnataka, India.

Dept. of Pharmacology, KLE College of Pharmacy, Vidyanagar, Hubballi-31, (A constituent unit of KLE Academy of Higher Education and Research, Belagavi) Karnataka, India.

出版信息

J Ayurveda Integr Med. 2021 Oct-Dec;12(4):657-662. doi: 10.1016/j.jaim.2021.07.020. Epub 2021 Nov 17.

Abstract

BACKGROUND

Efficacy of Anthracycline derivative Doxorubicin (Dox) has been proven in several malignancies such as breast cancer, Hodgkin and non-Hodgkin lymphoma, acute leukemia, lung, thyroid and ovarian cancer. However its clinical usefulness is restricted due to its cardiotoxicity and nephrotoxicity. Rosa centifolia belongs to family Rosaceae and in Ayurveda it is claimed for use in renal disorders. The main phyto-constituents of the plant are terpenoids, glycosides, flavonoids, tannins, phenolic compounds, pro-antroocyanides, pectin and riboflavin.

OBJECTIVE

To investigate the ameliorative role of ethanolic extract of petals of R. centifolia in doxorubicin induced nephrotoxicity in rats.

MATERIALS AND METHODS

Nephrotoxicity was produced by administration of doxorubicin (2.5 mg/kg b.w., i.p. alternate day) in six equal injections for two weeks to achieve a cumulative concentration of 15 mg/kg. Low (LERC - 100 mg/kg p.o.) and high (HERC - 200 mg/kg p.o.) dosees of ethanolic extract of petals of R. centifolia was administered as a pretreatment prior to doxorubicin administration. The general parameters such as body weight, food and water intake were measured throughout the study period. Serum biomarkers such as blood urea nitrogen (BUN), serum creatinine and albumin were measured before treatment and at the end of the experiments. Anti-oxidant enzymes such as glutathione (GSH), melonldehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) were monitored after the last dose. Nephrotoxicity was assessed through histopathological analysis.

RESULTS

The repeated administration of doxorubicin produces several morphological changes including reduction in the body weight as well as decreased food and water consumption. Serum biomarkers such as BUN, serum creatinine were increased and albumin concentration was decreased. The GSH, SOD and CAT concentrations were decreased, whereas MDA concentration was increased. Deteriorating changes in the histological architecture of kidney tissue were observed. In the LERC and HERC pretreated groups following changes were observed in dose dependent manner: increase in body weight, food and water intake (p < 0.05 and p < 0.01), decrease in the BUN (p < 0.05 and p < 0.01) and serum creatinine (p < 0.05 and p < 0.05) concentrations respectively. The significant increase in the albumin (p < 0.01) concentration was observed only in HERC. The pretreatment with LERC and HERC increased the antioxidant enzymes concentrations i.e. GSH (p < 0.01 and p < 0.01), SOD (p < 0.01 and p < 0.01), CAT (p < 0.05 and p < 0.01) and decreased the MDA concentration (p < 0.05 and p < 0.01) respectively. Histopathological studies showed that the pretreatment with low and high doses of ethanolic extract of petals of Rosa centifolia LERC and HERC groups minimized the tubular damage and reduced the inflammation as compared to doxorubicin treated group.

CONCLUSION

The biochemical and histopathological data from the present study clearly support the nephroprotective effect of ethanolic extract of petals of R. centifolia, which might be credited to its anti-oxidant property.

摘要

背景

蒽环类衍生物阿霉素(Dox)已被证实在多种恶性肿瘤中具有疗效,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。然而,由于其心脏毒性和肾毒性,其临床应用受到限制。百叶蔷薇属于蔷薇科,在阿育吠陀医学中,它被宣称可用于治疗肾脏疾病。该植物的主要植物成分包括萜类、糖苷、黄酮类、单宁、酚类化合物、原花青素、果胶和核黄素。

目的

研究百叶蔷薇花瓣乙醇提取物对阿霉素诱导的大鼠肾毒性的改善作用。

材料与方法

通过腹腔注射阿霉素(2.5 mg/kg体重,隔日一次),共注射六次,持续两周,以达到15 mg/kg的累积浓度,从而诱导产生肾毒性。在给予阿霉素之前,预先给予低剂量(LERC - 100 mg/kg口服)和高剂量(HERC - 200 mg/kg口服)的百叶蔷薇花瓣乙醇提取物。在整个研究期间测量体重、食物和水摄入量等一般参数。在治疗前和实验结束时测量血清生物标志物,如血尿素氮(BUN)、血清肌酐和白蛋白。在最后一剂后监测抗氧化酶,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)。通过组织病理学分析评估肾毒性。

结果

重复给予阿霉素会导致多种形态学变化,包括体重减轻以及食物和水摄入量减少。血清生物标志物如BUN、血清肌酐升高,白蛋白浓度降低。GSH、SOD和CAT浓度降低,而MDA浓度升高。观察到肾组织的组织结构出现恶化变化。在LERC和HERC预处理组中,观察到以下剂量依赖性变化:体重、食物和水摄入量增加(p < 0.05和p < 0.01),BUN(p < 0.05和p < 0.01)和血清肌酐(p < 0.05和p < 0.05)浓度分别降低。仅在HERC组中观察到白蛋白浓度显著升高(p < 0.01)。LERC和HERC预处理分别增加了抗氧化酶浓度,即GSH(p < 0.01和p < 0.01)、SOD(p < 0.01和p < 0.01)、CAT(p < 0.05和p < 0.01),并降低了MDA浓度(p < 0.05和p < 0.01)。组织病理学研究表明,与阿霉素治疗组相比,低剂量和高剂量的百叶蔷薇花瓣乙醇提取物预处理组(LERC和HERC组)使肾小管损伤最小化,并减轻了炎症。

结论

本研究的生化和组织病理学数据清楚地支持了百叶蔷薇花瓣乙醇提取物的肾保护作用,这可能归因于其抗氧化特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c489/8642703/eb3eec8c6fcd/gr1.jpg

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