Synergistic Neuroprotective Effects of Hesperetin and Naringenin against Benzo[a]pyrene-induced Brain Injury

Abstract

Benzo[a]pyrene (BaP), an environmental contaminant that is lipophilic and can cross the blood-brain barrier, has been investigated for its neurotoxic effects. Our study examined the combined therapeutic effect of Hesperetin (HPN) and Naringenin (NAR) against BaP-induced neuronal injury. Twenty-eight adult Wistar strain (n=8) in each cohort received corn oil alone as the control. BaP alone and other test groups received BaP with HPN or BaP with NAR for 14 days. Following this, antioxidant enzymes, oxidative-inflammatory indices, and pathological assessment of brain tissue were performed. BaP treatment resulted in a marked reduction in CAT (67%), SOD (72%), GPX (56%), GST (66%), and GSH (55%) levels, accompanied by a concomitant increase in markers of tissue damage, including LPO (76%) and RONS (69%). Additionally, proinflammatory indices, including NO 69%, MPO 60%, IL-1β, and TNF-α 58% and 62%, respectively, were elevated in BaP-exposed rats (p < 0.01) compared to control. However, the synergistic effect of NAR + HPN was able to mitigate the observed changes. Histological examination of the combined therapeutic flavonoids showed significant effects against BaP-treated rats and restored antioxidant enzyme levels to near-baseline levels (within 90–95% of control; p < 0.01). Also reduced LPO and RONS by 50% and suppressed TNF-α and IL-1β. Natural compounds found in citrus, NAR, and HPN, conferred a synergistic protection against environmental pollutants and a probable carcinogen, BaP-induced brain injury. The chemopreventive efficacy was initiated by the upregulation of antioxidant defences, which suppressed oxidative inflammation and preserved brain histoarchitecture.