Unveiling the mechanism of sericin and hydroxychloroquine in suppressing lung oxidative impairment and early carcinogenesis in diethylnitrosamine-induced mice by modulating PI3K/Akt/Nrf2/NF-κB signaling pathway

Abstract

This study sheds light on the ameliorative influence of combined sericin and hydroxychloroquine (HQ) on mitigating diethylnitrosamine (DEN)-induced lung oxidative impairment and inflammation, thereby precluding early carcinogenic episodes in mice. Besides, the pivotal role of sericin and HQ in controlling the PI3K/Akt/Nrf2/NF-κB signaling pathway was probed. Therefore, male Swiss albino mice were assigned to different groups and treated with different drugs. Oxidative stress and inflammatory biomarkers, in addition to the expression of PI3K and Akt genes were evaluated in lung tissues. Treatment with DEN disturbed the redox homeostasis associated with inflammation in the lungs. Conversely, sericin combined with HQ remarkably upregulated Nrf2 expression in the lungs associated with significant ameliorations of antioxidant factors, including SOD, GST, GSH, and MDA. Furthermore, sericin and HQ abated inflammation instigated by DEN through downregulating NF-κB and inflammatory biomarkers, including TNF-α and IL-6, with an increase in IL-10. Importantly, sericin and HQ treatment significantly downregulated PI3K and Akt expression. Immunohistochemical investigations demonstrated marked diminutions in Ki-67 and p53 expressions in animals cotreated with sericin and HQ compared to the DEN-treated group, inhibiting lung cancer progression. Histopathological and ultrastructural anomalies were detected in lung tissues from the DEN group, while significant enhancements were perceived in lung tissues treated with sericin and HQ. Our findings emphasized that the combinatorial therapy of sericin and HQ could orchestrate the PI3K/Akt/Nrf2/NF-κB signaling pathway in the lungs, counteracting oxidative stress, inflammation, and uncontrolled cellular proliferation and sustaining lung structures. Furthermore, they could serve as anticancer agents, hindering lung cancer progression.