Nanocurcumin Improves Lipid Status, Oxidative Stress, and Function of the Liver in Aluminium Phosphide-Induced Toxicity: Cellular and Molecular Mechanisms

Abstract

Background: The present study aimed to evaluate the effect of nanocurcumin and curcumin on liver transaminases, lipid profile, oxidant and antioxidant system, and pathophysiological changes in aluminium phosphide (ALP) induced hepatoxicity. Material and Methods. In this experimental study, thirty-six male Wistar rats were randomly divided into six groups curcumin (Cur), nanocurcumin (Nanocur), ALP, ALP+Cur, and ALP+Nanocur. All treatments were performed by oral gavage for seven days. After treatment, animals were sacrificed, and liver and blood samples were taken. Serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), total bilirubin, cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were measured by photometric methods. Total antioxidant capacity (TAC) and malondialdehyde (MDA) as parameters of oxidative stress and mRNA expression of the nonenzyme protein including Sirtuin 1 (STR1), Forkhead box protein O1 (FOXO1) and protein O3 (FOXO3), catalase (CAT), and glutathione peroxidase (GPX) as the enzyme protein in homogenized tissues have been investigated. A histologist analyzed liver tissue sections after staining with hematoxylin-eosin.

Results: In the aluminium phosphide group, there was a significant increase in MDA, ALT, AST, and AP and total bilirubin, cholesterol, triglyceride, LDL, and VLDL; AST, ALT, total bilirubin, LDL, VLDL, cholesterol, and MDA were significantly decreased; and HDL and TAC were significantly increased compared to ALP (P < 0.05). In the ALP+Nanocur group, ALT, AST, ALP, total bilirubin, cholesterol, LDL, VLDL, triglyceride, and MDA were significantly decreased and HDL and TAC were increased significantly (P < 0.05). The effect of nanocurcumin on controlling serum levels of LDL, VLDL, triglyceride, and MDA in ALP-poisoned rats was significantly more than curcumin (P < 0.05). The ALP group had significant changes in genes SIRT1, FOXO1a, FOXO3a, CAT, and GPX compared to healthy controls (P < 0.05). Nanocurcumin mice expressed more SIRT1, FOXO1a, CAT, and GPX genes than controls, and curcumin-treated mice expressed more SIRT1 and FOXO1a genes (P < 0.05). Histopathological findings also indicated a more significant protective effect of nanocurcumin relative to curcumin against ALP-induced hepatotoxicity.

Conclusion: Nanocurcumin significantly protects the liver against aluminum phosphide toxicity. It is suggested that nanocurcumin-based drugs be developed to reduce the toxic effects of ALP in poisoned patients.

Figure 1

Comparison of serum stress oxidative biomarkers in aluminum phosphide-induced liver toxicity in male rats. Data are expressed as mean ± SD. ^∗∗P ≤ 0.01 vs. Control group. ^##P ≤ 0.01 vs. ALP group. ^††P ≤ 0.01 difference between ALP+Cur and ALP+Nanocur groups.

Figure 2

Comparison of serum liver biomarkers in aluminum phosphide-induced liver toxicity in male rats. Data are expressed as mean ± SD. ^∗∗P ≤ 0.01 and ^∗∗∗P ≤ 0.001 vs. Control group, ^#P ≤ 0.05, ^##P ≤ 0.01, and ^###P ≤ 0.001 vs. ALP group. ^†P ≤ 0.05 and ^††P ≤ 0.01 difference between ALP+Cur and ALP+Nanocur groups.

Figure 3

Comparison of lipid profiles in aluminum phosphide-induced liver toxicity in male rats. Data are expressed as mean ± SD. ^∗P ≤ 0.05, ^∗∗P ≤ 0.01, and ^∗∗∗P ≤ 0.001 vs. Control group, ^#P ≤ 0.05, ^##P ≤ 0.01, and ^###P ≤ 0.001 vs. ALP group. ^†P ≤ 0.05 and ^††P ≤ 0.01 difference between ALP+Cur and ALP+Nanocur groups.

Figure 4

The expression of SIRT1, FOXO1a, FOXO3a, CAT, and GPX genes in the study groups. Data are reported according to mean ± SD: C: control; ALP: aluminum phosphide; Cur: curcumin; Ncur: nanocurcumin. A: significant compared to healthy control group; b: significant compared to the poisoned control group (^∗P < 0.05, ^∗∗P < 0.01).

Figure 5

Histopathological evaluation of liver tissue in ALP-poisoned male rats using hematoxylin-eosin staining. (a) Control group, (b) curcumin group, (c) nanocurcumin group, (d) aluminum phosphide group, (e) ALP+Cur group, (f) ALP+Nanocur group. H: hepatocytes; CV: central vein; Syn: sinusoids; Inf: infiltration; and Nec: necrosis.