Captopril inhibits the pulmonary toxicity of paraquat in rats

Abstract

<jats:p> Paraquat (PQ) is a herbicide that is very toxic to all living organisms. It generates free radicals and leads to acute or chronic lung injury. Free radicals are often associated with fibrogenesis, which occurs in various disease states. The purpose of this study was to determine whether captopril prevents paraquat toxicity in lung tissue. Paraquat alone increased the level of lipid peroxidation (LPO) and the activity of superoxide dismutase (SOD) after 4, 12, 24 and 72 h of administration. Also, the level of hydroxyproline showed an increase after 24 h of paraquat administration. However, paraquat also decreased the level of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). Captopril (50 mg/kg i.p.) and paraquat were simultaneously injected (40 mg/kg i.p.), and the captopril injection 1 h after paraquat ameliorated the biochemical toxicity induced by paraquat. This was evidenced by a significant reduction in LPO and balancing the endogenous anti-oxidant capacity by normalizing the activities of SOD and GSH-Px and the GSH content in the lung tissue. Moreover, captopril injection prevented the increase of hydroxypro-line content as an index of lung fibrosis. From these results, the beneficial effects of captopril on paraquat toxicity appear to be through enhancement of the endogenous anti-oxidant system preventing the lung fibrosis. </jats:p>

The apoptosis/necrosis transition in cerebellar granule cells depends on the mutual relationship of the antioxidant and the proteolytic systems which regulate ROS production and cytochrome c release en route to death

“…As this compound, when used in different experimental systems, shows a variety of effects, including prevention of ROS dependent toxicity (Abd El‐Aziz et al . 2001; Candan and Alagozlu 2001) and, importantly, of caspase‐3 activation (Uhal et al . 1998), control was made that under our conditions it has no significant effect on caspase activity.…”

Reduction of Morbidity and Mortality by Statins, Angiotensin-Converting Enzyme Inhibitors, and Angiotensin Receptor Blockers in Patients With Chronic Obstructive Pulmonary Disease

“…In addition, and of special importance, these agents also seem to affect pulmonary disease itself, as suggested by reduced hospitalizations for COPD. This is possibly due to mitigation of pulmonary injury by statins and drugs affecting angiotensin II (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). The possibility that these classes of drugs have dual cardiopulmonary protective properties has not been seriously considered in discussions of new therapies for COPD (32).…”

“…In addition, we hypothesized that statins (hydroxymethylglutaryl CoA reductase inhibitors [HMG-CoA]) and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), through pleiotropic mechanisms, might also modify outcomes directly attributed to lung disease itself (11). The latter conjecture is based on mechanistic studies showing the potential importance of these drugs in mitigating diverse forms of lung injury (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Accordingly, we used population databases to explore the impact of these drugs on the outcome of patients with COPD with respect to both pulmonary and CV events as well as to overall mortality.…”

Oxidative stress and glutathione in TGF-β-mediated fibrogenesis

“…Paraquat is a broad spectrum contact herbicide that is known to cause progressive pulmonary fibrosis in human and animals [294, 295]. It has been reported that paraquat-induced lung fibrosis is associated with a decline in GSH content in the lung [286, 295]. A significant depletion of GSH was also observed in the lung and red blood cells in chrysotile-exposed rats during different developmental stages of asbestosis [296].…”