Raheem Noor Majid, Mohammed Ali Mahmood Naza
Department of Pharmacology and Toxicology, College of Pharmacy, 275719University of Sulaimani, Sulaimaniyah, Iraq.
Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231155092. doi: 10.1177/09603271231155092.
The local renin-angiotensin system has been discovered in the eyes; thus, this study evaluates the Azilsartan effect in the retina and optic nerve toxicity induced by Cisplatin in vivo.
Forty-eight male rats were randomly assigned into six groups of 8 animals. Group 1 was healthy control that received 0.5 mL/day of 0.5% carboxymethyl cellulose (CMC) orally (PO). Group 2 received a single dose of the 7.0 mg/kg CIS intraperitoneally with 0.5 mL/day of 0.5% CMC-PO. Groups 3 and 4 received 3.5 and 7.0 mg/kg/day of AZIL-PO, respectively. Groups 5 and 6 received 3.5 and 7.0 mg/kg/day of AZIL-PO, respectively together with a single dose of 7.0 mg/kg of CIS-IP. The ocular tissue and serum estimated the TNF-α, NF-kβ, and Casp-3. A complete blood count was also measured, and the eye was sent for histological examination.
The administration of the 3.5 mg/kg AZIL significantly ( < 0.05) reduced the ocular tissue and serum TNF-α, NF-kB, and Casp-3 levels, when given to CIS treated group, while the 7.0 mg/kg AZIL does not. Additionally, azilsartan shows no negative impact on the CBC in rats. Finally, the eye histological examination showed a significant ( < 0.05) drop in the signs of inflammation and cellular degeneration, particularly after administration of the 3.5 mg/kg AZIL to the CIS-treated group.
A low dose of AZIL exerts an anti-inflammation and an anti-apoptotic effect through significant suppression of the pro-inflammatory mediators and an apoptotic biomarker by blocking the local angiotensin II type.
眼部已发现局部肾素 - 血管紧张素系统；因此，本研究评估阿齐沙坦对顺铂在体内诱导的视网膜和视神经毒性的作用。
48只雄性大鼠随机分为6组，每组8只动物。第1组为健康对照组，口服0.5%羧甲基纤维素（CMC），剂量为0.5 mL/天。第2组腹腔注射7.0 mg/kg顺铂，同时口服0.5% CMC，剂量为0.5 mL/天。第3组和第4组分别口服阿齐沙坦，剂量为3.5和7.0 mg/kg/天。第5组和第6组分别口服阿齐沙坦，剂量为3.5和7.0 mg/kg/天，同时腹腔注射7.0 mg/kg顺铂。检测眼组织和血清中的肿瘤坏死因子-α（TNF-α）、核因子-κB（NF-kβ）和半胱天冬酶-3（Casp-3）。还进行了全血细胞计数，并将眼睛送去做组织学检查。
给予顺铂治疗组3.5 mg/kg阿齐沙坦时，可显著（P<0.05）降低眼组织和血清中TNF-α、NF-kB和Casp-3水平，而7.0 mg/kg阿齐沙坦则无此作用。此外，阿齐沙坦对大鼠的全血细胞计数无负面影响。最后，眼部组织学检查显示炎症和细胞变性体征显著（P<0.05）下降，尤其是在给顺铂治疗组给予3.5 mg/kg阿齐沙坦后。
低剂量阿齐沙坦通过阻断局部血管紧张素II型，显著抑制促炎介质和凋亡生物标志物，发挥抗炎和抗凋亡作用。
