Evaluation of Protective Effects of Curcumin and Nanocurcumin on Aluminium Phosphide‑Induced Subacute Lung Injury in Rats: Modulation of Oxidative Stress through SIRT1/FOXO3 Signalling Pathway

Abstract

Objective Aluminum phosphide (AlP) is widely used to protect stored food products and grains from pests and rodents. The availability of AlP, especially in Asian countries it has become a desirable factor to commit suicide. The phosphine produced from ALP is a very reactive radical and a respiratory inhibitor that causes oxidative damage. There is no dedicated antidote or effective drug to manage AlP-induced lung toxicity. The present study aims to evaluate and compare the protective effects of curcumin and nanocurcumin on ALP‑induced subacute lung injury and determine the underlying mechanism. Methods Rats were exposed to AlP (2 mg/kg/day, orally)+curcumin or nanocurcumin (100 mg/kg/day, orally) for 7 days. Then rats were anesthetized and lung tissues were collected. Oxidative stress biomarkers, genes expression of antioxidant enzymes, participated genes in the SIRT1/FOXO3 pathway, and lung histopathology were assessed by biochemical and ELISA methods, Real-Time PCR analysis, and H&E staining. Results Curcumin and nanocurcumin produced a remarkable improvement in AlP-induced lung damage through reduction of MDA, induction of antioxidant capacity (TAC, TTG) and antioxidant enzymes (CAT, GPx), modulation of histopathological changes, and up-regulation of genes expression of SIRT1, FOXO3, FOXO1 in lung tissue. Conclusion Nanocurcumin had a significantly more protective effect than curcumin to prevent AlP-induced lung injury via inhibition of oxidative stress. Nanocurcumin could be considered a suitable therapeutic choice for AlP poisoning.

Regulation of Gene Expression through Food—Curcumin as a Sirtuin Activity Modulator

“…Additionally, in another rat model of COPD (cigarette smoke exposure combined with intratracheal administration of lipopolysaccharide), curcumin induced a reduction of oxidative stress and inflammation markers and increased the expression of SIRT3 [136]. Moreover, curcumin proved protective effects in a rat model of aluminum phosphide induced lung injury, modulated by a decrease in oxidative stress and an increased expression of SIRT1, FOXO1 and FOXO3 [137]. The protective effects were also confirmed in lymphocytes isolated from COPD patients, exposed to 1 µM curcumin, which increased SIRT1 expression and decreased steroid resistance, IFNγ and TNF-α production [138].…”

Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications

“…Fluoride is a toxic non-metallic element, and liver is considered one of the important target organs of fluorosis. The silent information regulator 1(SIRT1)/forkhead box O3 (FOXO3) pathway was involved in rats’ aluminum phosphide-induced acute lung injury [ 127 ]. Similarly, the SIRT1/FOXOs pathway could lead to lipid peroxidation and iron accumulation under fluorosis conditions, ultimately triggering ferroptosis [ 128 ].…”

Natural Phytochemicals as SIRT Activators—Focus on Potential Biochemical Mechanisms

“…In another rat model of COPD, curcumin reduced oxidative stress and inflammation markers while increasing the expression of SIRT3 [ 107 ]. Furthermore, curcumin presented protective capabilities in a rat model of aluminum phosphide-induced lung injury by decreasing oxidative stress and increasing the expression of SIRT1, FOXO1, and FOXO3 [ 108 ]. Similar positive results were observed in lymphocytes isolated from COPD subjects, where curcumin increased SIRT1 expression, reduced steroid resistance, and decreased the release of IFNγ and TNF-α.…”