Hegazy Ahmed Medhat, Farid Ayman Samir, Hafez Ahmed S, Eid Rania M, Nasr Soad M
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Aswan University, Sahari, Airport Way 81528, Aswan, Egypt.
Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh 13736, Qalyubia, Egypt.
Vet World. 2019 Dec;12(12):1903-1910. doi: 10.14202/vetworld.2019.1903-1910. Epub 2019 Dec 4.
The current study was designed to evaluate the potential hepatoprotective and immunomodulatory effects of copper-nicotinate complex (CNC) against methionine- and choline-deficient diet (MCDD)-induced fatty liver in rats.
Forty male Wistar rats were randomly allocated into one of four equal-sized groups (G1-G4). The G1 group was fed a balanced diet and kept under normal conditions; the G2 group received CNC orally at a dose of 0.043 mg/kg body weight, 3 times/week for 4 weeks, and a balanced diet; the G3 group was fed an MCDD for 4 weeks; and the G4 group was fed an MCDD and administered CNC at the same dose and route as G2. Blood samples were collected for the determination of serum enzyme activity. After 4 weeks of treatment, liver specimens were collected for the evaluation of the oxidative/antioxidative markers, cytokine gene expression, and histopathological examination.
CNC improved MCDD-induced liver dysfunctions by recovering serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities to their normal levels. The glutathione (GSH) level and superoxide dismutase (SOD) activity significantly decreased, while lipid peroxidation (as reflected by malondialdehyde [MDA]) markedly increased in the liver tissue of the MCDD group. After cotreatment with MCDD and CNC, the GSH level and SOD activity markedly increased and the MDA level significantly decreased to return to normal levels. After cotreatment with MCDD and CNC, significant downregulation of the mRNA expression of hepatic interleukin (IL)-1β, IL-4, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1 genes was found. Moreover, CNC reduced fatty liver complications by reducing the number of hepatic vacuolations, degenerative changes in the hepatocytes, and hemorrhage.
CNC has the potential to limit tissue injury and possibly prevent the progression to severe liver disease caused by an MCDD.
本研究旨在评估烟酸铜复合物（CNC）对蛋氨酸和胆碱缺乏饮食（MCDD）诱导的大鼠脂肪肝的潜在肝脏保护和免疫调节作用。
40只雄性Wistar大鼠随机分为4个等大的组（G1 - G4）。G1组给予均衡饮食并保持在正常条件下；G2组以0.043 mg/kg体重的剂量口服CNC，每周3次，共4周，并给予均衡饮食；G3组给予MCDD 4周；G4组给予MCDD并按与G2组相同的剂量和途径给予CNC。采集血样以测定血清酶活性。治疗4周后，采集肝脏标本以评估氧化/抗氧化标志物、细胞因子基因表达和组织病理学检查。
CNC通过将血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和γ-谷氨酰转移酶活性恢复到正常水平，改善了MCDD诱导的肝功能障碍。MCDD组肝组织中谷胱甘肽（GSH）水平和超氧化物歧化酶（SOD）活性显著降低，而脂质过氧化（以丙二醛[MDA]反映）显著增加。MCDD与CNC联合治疗后，GSH水平和SOD活性显著增加，MDA水平显著降低至正常水平。MCDD与CNC联合治疗后，发现肝白细胞介素（IL）-1β、IL-4、巨噬细胞炎性蛋白-1α和单核细胞趋化蛋白-1基因的mRNA表达显著下调。此外，CNC通过减少肝空泡化数量、肝细胞退行性变化和出血，减轻了脂肪肝并发症。
CNC有潜力限制组织损伤，并可能预防由MCDD引起的严重肝病的进展。
