Akhtar Muhammad Shoaib, Rehman Aziz-Ur-, Arshad Haroon, Malik Abdul, Fatima Muheer, Tabassum Tahira, Raza Abdul Rauf, Bukhsh Munnaza, Murtaza Mian Anjum, Mehmood Malik Hassan, Sultan Ayesha, Rasool Ghulam, Riaz Muhammad
Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, Pakistan.
Department of Pathobiology, College of Veterinary and Animal Sciences (Jhang Campus), University of Veterinary and Animal Sciences, Lahore, Pakistan.
Dose Response. 2021 Mar 15;19(1):1559325821996955. doi: 10.1177/1559325821996955. eCollection 2021 Jan-Mar.
The lack of safety and efficacy of existing hepatoprotective agents urge the need to explore novel hepatoprotective agents. The research work was planned to study the therapeutic potential of some newly synthesized chalcones against 4-acetaminophenol induced hepatotoxicity in rats. Male albino rats (N = 30) were divided into 6 groups of 5 animals each i.e. group I; Toxic control (4-acetaminophenol), group II; normal control (Normal saline), group III; Positive control (silymarin; 50 mg/kg bw) and groups IV-VI (test groups) treated with 3 chalcone analogues i-e 3a, 3f & 3 g (100, 150, 150 mg/kg bw, respectively). All the study group animals were administered with 4-acetaminophenol to induce hepatotoxicity except normal control. Following hepatotoxicity induction, test group animals were administered with selected doses of test compounds and toxic group animals left untreated. Liver enzymes including ALT, AST, ALP and serum bilirubin were determined photometrically. Antioxidant activities of test compounds were also determined. Histopathological examination of liver biopsies was also carried out through H & E staining. The test chalcones (, & ) significantly decreased the levels of liver enzymes and serum bilirubin toward normal and the pattern of results in the test group animals were comparable to silymarin administered animals indicating the hepatoprotective potential of test compounds. Moreover, the test chalcones (, & ) antagonized the effect of 4-acetaminophenol and thus, raised the catalase (CAT) and superoxide dismutase (SOD) while decreased the malondialdehyde (MDA) in experimental animals. The test chalcones (, & ) on histological examination of liver showed improvement of tissue morphology. The study concluded that the tested compounds have antioxidant potential and may act as hepatoprotective agent. However, in-depth studies are required to validate their safety and to elucidate the exact mechanism of action.
现有保肝药物缺乏安全性和有效性,促使人们去探索新型保肝药物。本研究旨在探讨一些新合成的查尔酮对大鼠4-氨基酚诱导的肝毒性的治疗潜力。将雄性白化大鼠(N = 30)分为6组,每组5只动物,即第一组为毒性对照组(4-氨基酚),第二组为正常对照组(生理盐水),第三组为阳性对照组(水飞蓟宾;50 mg/kg体重),第四至六组为试验组,分别用3种查尔酮类似物3a、3f和3g(分别为100、150、150 mg/kg体重)处理。除正常对照组外,所有研究组动物均给予4-氨基酚以诱导肝毒性。诱导肝毒性后,试验组动物给予选定剂量的受试化合物,毒性组动物不进行处理。通过比色法测定包括谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)和血清胆红素在内的肝酶。还测定了受试化合物的抗氧化活性。通过苏木精和伊红(H&E)染色对肝活检组织进行组织病理学检查。受试查尔酮(3a、3f和3g)使肝酶和血清胆红素水平显著降至正常,试验组动物的结果模式与给予水飞蓟宾的动物相当,表明受试化合物具有保肝潜力。此外,受试查尔酮(3a、3f和3g)拮抗了4-氨基酚的作用,从而提高了实验动物的过氧化氢酶(CAT)和超氧化物歧化酶(SOD)水平,同时降低了丙二醛(MDA)水平。受试查尔酮(3a、3f和3g)对肝脏的组织学检查显示组织形态有所改善。研究得出结论,受试化合物具有抗氧化潜力,可能作为保肝药物。然而,需要深入研究以验证其安全性并阐明确切的作用机制。