两种新型中药制剂在啮齿动物尿石症模型中的筛选

M. Khan, Satyendra Kumar, Arun Gupta, Sayeed Ahmad
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引用次数: 2

摘要

背景:肾结石形成或尿石症是一个复杂的过程,是肾脏启动子和抑制子失衡的结果。尿石症的复发也是患者面临的一个严重问题。并非所有用于预防尿石症的标准药物都对所有患者有效,而且许多药物都有副作用。本研究评价了两种新型中药制剂DRDC/AY/8080(片剂)和DRDC/AY/8081(糖浆剂)对28天乙二醇(EG)诱导的Wistar大鼠尿石症模型的抗尿石作用。材料与方法:随机分为5组(n = 6),对照组灌胃生理盐水,中毒组灌胃0.75% EG + 1% w/v氯化铵(AC),灌胃10 d,再灌胃0.75% w/v EG,灌胃18 d。各治疗组分别与DRDC/AY/8080 (265 mg/kg)、DRDC/AY/8081 (2.65 ml/kg)、标准品(2.65 ml/kg)口服共治疗28 d,毒理学组给予EG、AC。28 d后采集尿液、血液和肾脏组织。在尿中估计Ca2+, Mg2+, Na+和K+水平,在血清中估计肌酐和尿素水平,而在肾组织中测量脂质过氧化程度。此外,在尿液和肾脏组织中分别进行结晶尿和组织病理学评估。结果:毒理学组血清肌酐、尿素、组织脂质过氧化和尿Mg2+水平显著升高(P < 0.001),尿Na+和Ca2+水平显著降低(P < 0.001)。中毒组的组织病理学显示近端小管受损,有折光性晶体沉积,小管上皮丢失。从较低的血清肌酐、血尿素和过氧化脂质水平可以看出,片剂组和糖浆组均表现出肾保护活性。用片剂和糖浆制剂治疗也显示尿Na+、Ca2+和Mg2+水平显著升高(P < 0.001)。组织学上,片剂(AY/8080)和糖浆治疗对尿石症和肾毒性均有保护作用。结论:DRDC/AY/8080和DRDC/AY/8081两种中药制剂在治疗肾结石方面具有较大的潜力。
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Screening of two new herbal formulations in rodent model of urolithiasis
Background: Kidney stone formation or urolithiasis is a complex process that is a consequence of an imbalance between promoters and inhibitors in the kidneys. The recurrence of urolithiasis also represents a serious problem in patients. Not all standard pharmaceutical drugs used to prevent urolithiasis are effective in all patients, and many have adverse effects. The present study was undertaken to evaluate the antiurolithiatic potential of two new herbal formulations DRDC/AY/8080 (tablet) and DRDC/AY/8081 (syrup) against 28-day ethylene glycol (EG)-induced urolithiasis model in Wistar rats. Materials and Methods: Animals were divided into five groups (n = 6). The control group was given normal saline, and the toxicant group was given 0.75% EG with 1% w/v of ammonium chloride (AC) for 10 days followed by 0.75% w/v EG for next 18 days in drinking water. Treatment groups received respective oral co-treatment with DRDC/AY/8080 (265 mg/kg), DRDC/AY/8081 (2.65 ml/kg), and standard (2.65 ml/kg) for 28 days along with EG and AC as given in toxicant group. After 28th day urine, blood and kidney tissue were collected. Ca2+, Mg2+, Na+, and K+ levels were estimated in urine, creatinine, and urea levels were estimated in serum whereas the extent of lipid peroxidation was measured in kidney tissue. Further, crystalluria and histopathological evaluation were carried out in urine and kidney tissue, respectively. Results: Toxicant group showed significant elevation (P < 0.001 vs. control) in serum creatinine, blood urea, tissue lipid peroxide, and urinary Mg2+ levels and significant reduction in (P < 0.001 vs. control) urinary Na+ and Ca2+ levels. Histopathology of the toxicant group showed damaged proximal tubules with deposits of refractile crystals and loss of tubular epithelium. Both tablet and syrup treated groups showed nephroprotective activity as evident from lower serum creatinine, blood urea, and lipid peroxide levels. Treatment with tablet and syrup formulations also showed significant (P < 0.001 vs. toxicant) elevation in urinary Na+, Ca2+, and reduction in Mg2+ levels. Histologically, both tablet/AY/8080) and syrup treatment showed protected against urolithiasis and nephrotoxicity. Conclusion: It can be concluded that the two herbal formulations DRDC/AY/8080 and DRDC/AY/8081 possess significant potential in the management of renal calculi.
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