Effect of Telmisartan on Arsenic-Induced (Sub-chronic) Perturbations in Redox Homeostasis, Pro-inflammatory Cascade and Aortic Dysfunction in Wistar Rats.

ABSTRACT

An experimental study was conducted in male Wistar rats to explore the antioxidant potential of telmisartan (an AT1 receptor blocker) to overcome arsenic ('As')-induced perturbations in redox homeostasis pro-inflammatory cytokines, prostaglandin-E2 levels and aortic dysfunction in Wistar rats. Wistar rats were randomly divided into four groups of six each. Group-I served as untreated control, while group-II received sodium (meta) arsenite (NaAsO2) (10 mg/kg b.wt. p.o) for a period of 60 days. Experimental rats in group-III received treatment similar to group-II, but in addition received telmisartan (with 1% aqueous solution of Tween 80) @ 10 mg/kg b.wt. (p.o) for a similar duration, while rats in group-IV received telmisartan alone. Arsenic exposure resulted in significant (p < 0.05) elevation in the levels of superoxide anion ([Formula see text]) radicals (control 768.20 ± 126.77 vs group-II 1232.75 ± 97.85 pmol of NBT reduced/min/mg protein). Telmisartan administration showed significant (p < 0.05) reduction in [Formula see text] generation (815.34 ± 43.41 pmol of NBT reduced/min/mg protein). Sub-chronic exposure to 'As' significantly (p < 0.05) decreased the activities of SOD, CAT, GPx and GR activity and GSH levels in the aorta, thus induced lipid peroxidation (LPO) measured as measured in terms of thiobarbituric acid reactive substances (TBARS) called as malondialdehyde (MDA). However, the administration of telmisartan effectively countered the LPO (24.03 ± 1.18 nmol of MDA/g) on account of restoring the levels of aforesaid antioxidant defense system. Telmisartan administration effectively attenuated the 'As'-induced surge in pro-inflammatory cytokines (viz., IL-1ß, IL-6 and TNF-α) levels, as well as countered the activity of cyclooxygenase (COX2) as indicated by a significant (p < 0.05) decrease in PGE2 level in the aorta. In addition to it, there was a significant (p < 0.05) decrease in plasma angiotensin II (Ang-II) levels in experimental rats receiving telmisartan. Quantitative RT-PCR studies revealed that sub-chronic exposure to 'As' upregulated the Nox2 mRNA expression, but there was a 1.2-fold reduction in expression level upon co-administration of telmisartan. Histopathological examination revealed marked recovery from 'As'-induced disruption of tunica adventitia and loss of connective tissue in experimental rats receiving telmisartan. The study concludes that telmisartan can overcome aortic dysfunction induced by sub-chronic exposure to arsenic through drinking water in experimental rats through restoration of redox balance, attenuation of pro-inflammatory cytokines and mediators and downregulation of Nox2 mRNA expression.