Zeweil Mohamed M, Khafaga Asmaa F, Mahmoud Sahar F, Wasef Lamiaa, Saleh Hamida, Elrehim Attaa M Abd, Bassuoni Naglaa F, Alwaili Maha Abdullah, Saeedi Nizar H, Ghoneim Hanan A
Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.
Front Pharmacol. 2024 Feb 1;15:1348145. doi: 10.3389/fphar.2024.1348145. eCollection 2024.
7,12-dimethylbenz (a) anthracene (DMBA) is a harmful polycyclic aromatic hydrocarbon derivative known for its cytotoxic, carcinogenic, and mutagenic effects in mammals and other species. Annona muricata, L. (Graviola; GRV) is a tropical fruit tree traditionally well-documented for its various medicinal benefits. This investigation is the first report on the potential antioxidant and antinfammatory reno-protective impact of GRV against DMBA-induced nephrotoxicity in rats. Forty male albino rats were allocated into four equal groups (n = 10). The 1st group served as the control, the 2nd group (GRV) was gastro-gavaged with GRV (200 mg/kg b.wt), the 3rd group (DMBA) was treated with a single dose of DMBA (15 mg/kg body weight), and the 4th group (DMBA + GRV) was gastro-gavaged with a single dose of DMBA, followed by GRV (200 mg/kg b.wt). The GRV administration was continued for 8 weeks. Results revealed a significant improvement in renal function, represented by a decrease in urea, creatinine, and uric acid (UA) in the DMBA + GRV group. The antioxidant potential of GRV was confirmed in the DMBA + GRV group by a significant decline in malondialdehyde (MDA) and a significant increase in catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), and reduced glutathione (GSH) compared to DMBA-intoxicated rats; however, it was not identical to the control. Additionally, the antiinflammatory role of GRV was suggested by a significant decline in mRNA expression of cytochrome P450, family 2, subfamily e, polypeptide 1 (CYP2E1), tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1β) in the DMBA + GRV group. Moreover, GRV improved the histopathologic and immunohistochemical expression of TNF-α, CYP450, and IL1β in DMBA-intoxicated kidney tissue. Conclusively, GRV is a natural medicinal product that can alleviate the renal injury resulting from environmental exposure to DMBA. The reno-protective effects of GRV may involve its anti-inflammatory and/or antioxidant properties, which are based on the presence of phytochemical compounds such as acetogenins, alkaloids, and flavonoids.
7,12 - 二甲基苯并(a)蒽（DMBA）是一种有害的多环芳烃衍生物，以其对哺乳动物和其他物种的细胞毒性、致癌性和致突变性而闻名。番荔枝（刺果番荔枝；GRV）是一种热带果树，传统上有多种药用功效的详细记载。本研究首次报道了GRV对DMBA诱导的大鼠肾毒性的潜在抗氧化和抗炎性肾保护作用。将40只雄性白化大鼠分成四个相等的组（n = 10）。第1组作为对照组，第2组（GRV组）经胃灌胃给予GRV（200mg/kg体重），第3组（DMBA组）用单剂量的DMBA（15mg/kg体重）处理，第4组（DMBA + GRV组）先经胃灌胃单剂量的DMBA，随后给予GRV（200mg/kg体重）。GRV给药持续8周。结果显示，DMBA + GRV组的肾功能有显著改善，表现为尿素、肌酐和尿酸（UA）降低。与DMBA中毒大鼠相比，DMBA + GRV组中丙二醛（MDA）显著下降，过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽S转移酶（GST）和还原型谷胱甘肽（GSH）显著增加，证实了GRV的抗氧化潜力；然而，与对照组并不相同。此外，DMBA + GRV组中细胞色素P450 2E1（CYP2E1）、肿瘤坏死因子 - α（TNF - α）和白细胞介素1β（IL - 1β）的mRNA表达显著下降，提示了GRV的抗炎作用。此外，GRV改善了DMBA中毒肾组织中TNF - α、CYP450和IL1β的组织病理学和免疫组化表达。总之，GRV是一种天然药物产品，可减轻因环境暴露于DMBA而导致的肾损伤。GRV的肾保护作用可能涉及其抗炎和/or抗氧化特性，这基于植物化学成分如番荔枝内酯、生物碱和黄酮类化合物的存在。
