Azilsartan suppresses the antiapoptotic biomarker and pro-inflammatory cytokines in rat model of cisplatin-induced retinal and optic nerve toxicity

• Published in: Human & experimental toxicology 2023-01, Vol.42, p.9603271231155092-9603271231155092
• Main Authors: Raheem, Noor Majid, Mohammed Ali Mahmood, Naza
• Format: Article
• Language: English
• Subjects: Angiotensin; Angiotensin II; Animals; Apoptosis; Biocompatibility; Biomarkers; Biomarkers - metabolism; Carboxymethyl cellulose; Carboxymethylcellulose; Cellulose; Cisplatin; Cisplatin - toxicity; Cytokines; Degeneration; Eye; Eye (anatomy); In vivo methods and tests; Inflammation; Male; Nerves; NF-kappa B - metabolism; NF-κB protein; Optic nerve; Optic Nerve - pathology; Oxidative Stress; Rats; Renin; Retina - metabolism; Toxicity; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/09603271231155092

Background 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. Methodology 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. Results The administration of the 3.5 mg/kg AZIL significantly (p < 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 (p < 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. Conclusion 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