Naringenin Ameliorates Lipopolysaccharide-Induced Kidney and Lung Injuries in Mice: Decisive Role of IL-1β, IL-6, IL8, and TNF-α

Cytokine storms are a major contributor to acute respiratory failure, causing numerous organ dysfunction, including kidney damage, as a result of inflammation-induced tubular injury, particularly evident in COVID-19 infections. This occurrence poses a global health risk. Experimental evidence suggests that naringenin, a natural flavonoid, has a variety of biological activities. The present study was conducted to examine the protective effects of naringenin in lipopolysaccharide (LPS)-induced lung and kidney injuries in mice and determine its relationship with the suppression of pro-inflammatory mediators. Forty-eight Swiss albino male mice were divided into four groups. Group I received 0.9% normal saline, Group II received 5 mg/kg LPS only, and Groups III and IV received 50 or 100 mg/kg naringenin, respectively, one hour before LPS administration. The effects of naringenin, vehicle, or LPS administration on mortality rate, pro-inflammatory cytokine (IL-6, IL-1, IL-8, and TNF-α) levels, and lung/renal histological changes were evaluated after 48 hours. The results showed that the naringenin-treated groups exhibited a significant (p ≤ 0.01) reduction in pro-inflammatory cytokine levels compared to Group II. Histological examinations revealed that mice in Group II displayed significant (p ≤ 0.01) lung and renal tissue injuries, while Groups III and IV exhibited a significant (p ≤ 0.01) reduction in pulmonary and renal injuries, as demonstrated by improved macroscopic scores and reduced mortality. The findings of this study strongly suggest that naringenin has potent protective effects in mice against LPS-induced lung damage and associated kidney dysfunction. Consequently, naringenin has promise as a human anti-cytokine storm therapeutic agent.