Modulatory effects of morin on NF-κB/TNF-α and apoptotic signaling against lead-induced hepatotoxicity: an in vivo and in silico study

Abstract

The global prevalence of lead exposure has escalated, posing significant occupational and ecological health risks. Morin, a naturally occurring flavonoid found in various dietary sources, exhibits notable antioxidant and anti-inflammatory properties. The present study was designed to evaluate the hepatotoxic effects of lead exposure and the anti-inflammatory and anti-apoptotic effects of morin in the hepatic tissue of rats. Experimental results demonstrated that intragastric administration of lead (30 mg/kg b.wt) for 28 days significantly induced pronounced inflammatory responses, as indicated by elevated mRNA expression of NF-κB, TNF-α and IL-1β. Additionally, lead exposure resulted in the upregulation of pro-apoptotic markers, such as Bax and caspase-3 and concomitant downregulation of the anti-apoptotic marker Bcl-2. In contrast, morin treatment (50 mg/kg b.wt, 28 days) significantly alleviated inflammation, inhibited apoptotic pathways and maintained histoarchitecture in the hepatic tissues of rats subjected to lead intoxication. In silico evaluation also revealed strong binding affinities of morin with key inflammatory and apoptotic targets, suggesting potential molecular interactions that may contribute to its observed protective effects. Collectively, these results underscore the potential of morin in modulating molecular responses associated with lead-induced hepatotoxicity,