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AHPL/AYTAB/0613片对Wistar白化大鼠四氯化碳、乙醇和对乙酰氨基酚诱导的肝毒性模型的肝保护活性的药理学评价。

Pharmacological Evaluation of Hepatoprotective Activity of AHPL/AYTAB/0613 Tablet in Carbon Tetrachloride-, Ethanol-, and Paracetamol-Induced Hepatotoxicity Models in Wistar Albino Rats.

作者信息

Nipanikar Sanjay U, Chitlange Sohan S, Nagore Dheeraj

机构信息

R and D Center, Ari Healthcare Private Limited, Hinjewadi, Pune, Maharashtra, India.

Department of Pharmaceutical Chemistry and Quality Assurance Tech, Padmashree Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pune, Maharashtra, India.

出版信息

Pharmacognosy Res. 2017 Dec;9(Suppl 1):S41-S47. doi: 10.4103/pr.pr_44_17.

Abstract

BACKGROUND

Hepatotoxicity ultimately leads to liver failure. Conventional treatment options for hepatotoxicity are limited and not safe.

OBJECTIVE

Formulation AHPL/AYTAB/0613 is developed to provide safer and effective hepatoprotective drug of natural origin. A study was conducted to evaluate hepatoprotective activity of AHPL/AYTAB/0613 (three dosages) in comparison with marketed formulations in carbon tetrachloride (CCl), ethanol, and paracetamol-induced hepatotoxicity in Wistar albino rats.

MATERIALS AND METHODS

Three separate studies were conducted in models of CCl, ethanol, and paracetamol-induced hepatotoxicity. Seven groups of animals were studied comparatively to evaluate the efficacy of AHPL/AYTAB/0613 in low, medium, and high dosage in comparison with silymarin and a marketed polyherbal formulation. The drugs were orally administered to rats for 10 days in CCl model and for 14 days in ethanol and paracetamol models. Animals were weighed periodically. After the study period, blood was tested for serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin, and total protein levels. Liver tissue of sacrificed animals was examined histopathologically.

RESULTS

All the test formulations including all three dosages of AHPL/AYTAB/0613, significantly reduced levels of SGOT, SGPT, ALP, total bilirubin, in CCl, ethanol, and paracetamol-induced hepatotoxicity models. There was significant increase in total protein level in all the tested formulations. All the test formulations effectively preserved the structural integrity of the hepatocellular membrane and liver cell architecture damaged by CCl, ethanol, and paracetamol. When compared between groups, no statistically significant difference was observed. It can be concluded that AHPL/AYTAB/0613 possesses hepatoprotective activity in CCl, ethanol, and paracetamol-induced hepatotoxicity in rats.

CONCLUSION

AHPL/AYTAB/0613 can be effectively used as a hepatoprotective agent in the management of hepatitis caused due to various toxins.

SUMMARY

A polyherbal formulation AHPL/AYTAB/0613 containing - extract, extract, extract, extract, extract, extract, extract, and extract was assessed for its hepatoprotective activity. This activity was tested in carbon tetrachloride (CCl), ethanol, and paracetamol-induced hepatotoxicity models in Wistar albino rats in comparison with two marketed formulations. It was observed that AHPL/AYTAB/0613 significantly reduced levels of serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, total bilirubin and also significantly increased total protein level. All the test formulations effectively preserved the structural integrity of the hepatocellular membrane and liver cell architecture damaged by CCl, ethanol, and paracetamol. When compared between groups, no statistically significant difference was observed. Therefore, it was concluded that AHPL/AYTAB/0613 possesses hepatoprotective activity in CCl, ethanol, and paracetamol-induced hepatotoxicity in rats. CCl: Carbon tetrachloride, SGOT: Serum glutamic-oxaloacetic transaminase, SGPT: Serum glutamic pyruvi transaminase, ALP: Alkaline phosphatase, UDCA: Ursodeoxycholic acid, US: United States, FDA: Food and Drug Administration, PBC: Primary biliary cirrhosis, GSTA1: Glutathione S-transferase A1, GSH: Glutathione, GPx: Glutathione peroxidase, GST: Glutathione S-transferases.

摘要

背景

肝毒性最终会导致肝衰竭。肝毒性的传统治疗选择有限且不安全。

目的

研发AHPL/AYTAB/0613制剂,以提供更安全有效的天然来源肝保护药物。开展一项研究,评估AHPL/AYTAB/0613(三种剂量)在四氯化碳(CCl)、乙醇和对乙酰氨基酚诱导的Wistar白化大鼠肝毒性模型中的肝保护活性,并与市售制剂进行比较。

材料与方法

在CCl、乙醇和对乙酰氨基酚诱导的肝毒性模型中分别开展三项研究。比较研究七组动物,以评估AHPL/AYTAB/0613低、中、高剂量与水飞蓟素和一种市售多草药制剂相比的疗效。在CCl模型中,药物经口给予大鼠10天;在乙醇和对乙酰氨基酚模型中,给药14天。定期称动物体重。研究期结束后,检测血液中的血清谷氨酸草酰乙酸转氨酶(SGOT)、血清谷氨酸丙酮酸转氨酶(SGPT)、碱性磷酸酶(ALP)、总胆红素和总蛋白水平。对处死动物的肝脏组织进行组织病理学检查。

结果

所有受试制剂,包括AHPL/AYTAB/0613的三种剂量,在CCl、乙醇和对乙酰氨基酚诱导的肝毒性模型中均显著降低了SGOT、SGPT、ALP和总胆红素水平。所有受试制剂的总蛋白水平均显著升高。所有受试制剂均有效维持了被CCl、乙醇和对乙酰氨基酚破坏的肝细胞膜和肝细胞结构的完整性。组间比较时,未观察到统计学显著差异。可以得出结论,AHPL/AYTAB/0613在大鼠CCl、乙醇和对乙酰氨基酚诱导的肝毒性中具有肝保护活性。

结论

AHPL/AYTAB/0613可有效用作治疗由各种毒素引起的肝炎的肝保护剂。

总结

评估了一种含有 - 提取物、提取物、提取物、提取物、提取物、提取物、提取物和提取物的多草药制剂AHPL/AYTAB/0613的肝保护活性。与两种市售制剂相比,在Wistar白化大鼠的四氯化碳(CCl)、乙醇和对乙酰氨基酚诱导的肝毒性模型中测试了该活性。观察到AHPL/AYTAB/0613显著降低了血清谷氨酸草酰乙酸转氨酶、血清谷氨酸丙酮酸转氨酶、碱性磷酸酶、总胆红素水平,且总蛋白水平也显著升高。所有受试制剂均有效维持了被CCl、乙醇和对乙酰氨基酚破坏的肝细胞膜和肝细胞结构的完整性。组间比较时,未观察到统计学显著差异。因此,得出结论,AHPL/AYTAB/0613在大鼠CCl、乙醇和对乙酰氨基酚诱导的肝毒性中具有肝保护活性。CCl:四氯化碳,SGOT:血清谷氨酸草酰乙酸转氨酶,SGPT:血清谷氨酸丙酮酸转氨酶,ALP:碱性磷酸酶,UDCA:熊去氧胆酸,US:美国,FDA:食品药品监督管理局,PBC:原发性胆汁性肝硬化,GSTA1:谷胱甘肽S-转移酶A1,GSH:谷胱甘肽,GPx:谷胱甘肽过氧化物酶,GST:谷胱甘肽S-转移酶

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468b/5757324/22ec3067615c/PR-9-41-g003.jpg

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