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

Abstract

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

Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways

“…In this study, cisplatin-induced histological alterations in the optic nerve include inflammation and apoptosis. Previous studies have reported similar alterations (Icel et al, 2018 ; Raheem and Mohammed Ali Mahmood, 2023 ). The current cytological alterations in the optic nerve after cisplatin treatment could be attributed to endoplasmic stress and the inhibition of autophagy.…”

Azilsartan Attenuates 3-Nitropropinoic Acid-Induced Neurotoxicity in Rats: The Role of IĸB/NF-ĸB and KEAP1/Nrf2 Signaling Pathways

“…Azilsartan (Azil) is an angiotensin II type 1 receptor blocker (ARB) that is used as an antihypertensive drug [ 27 ]. Azil has been shown to possess anti-inflammatory, anti-oxidant and anti-apoptotic effects that are associated with neuroprotection via blocking brain angiotensin II type 1 receptors (AT1R) [ 28 – 31 ]. Besides, the downstream signalling pathway of renin–angiotensin–aldosterone system (RAS) has been associated with NF-kB activation [ 32 ].…”