Coenzyme Q10-Loaded Albumin Nanoparticles Protect against Redox Imbalance and Inflammatory, Apoptotic, and Histopathological Alterations in Mercuric Chloride-Induced Hepatorenal Toxicity in Rats

Abstract

Exposure to mercuric chloride (HgCl₂), either accidental or occupational, induces substantial liver and kidney damage. Coenzyme Q10 (CoQ10) is a natural antioxidant that also has anti-inflammatory and anti-apoptotic activities. Herein, our study aimed to investigate the possible protective effects of CoQ10 alone or loaded with albumin nanoparticles (CoQ10NPs) against HgCl₂-induced hepatorenal toxicity in rats. Experimental animals received CoQ10 (10 mg/kg/oral) or CoQ10NPs (10 mg/kg/oral) and were injected intraperitoneally with HgCl₂ (5 mg/kg; three times/week) for two weeks. The results indicated that CoQ10NP pretreatment caused a significant decrease in serum liver and kidney function markers. Moreover, lowered MDA and NO levels were associated with an increase in antioxidant enzyme activities (SOD, GPx, GR, and CAT), along with higher GSH contents, in both the liver and kidneys of intoxicated rats treated with CoQ10NPs. Moreover, HgCl₂-intoxicated rats that received CoQ10NPs revealed a significant reduction in the hepatorenal levels of TNF-α, IL-1β, NF-κB, and TGF-β, as well as an increase in the hepatic level of the fibrotic marker (α-SMA). Notably, CoQ10NPs counteracted hepatorenal apoptosis by diminishing the levels of Bax and caspase-3 and boosting the level of Bcl-2. The hepatic and renal histopathological findings supported the abovementioned changes. In conclusion, these data suggest that CoQ10, alone or loaded with albumin nanoparticles, has great power in reversing the hepatic and renal tissue impairment induced by HgCl₂ via the modulation of hepatorenal oxidative damage, inflammation, and apoptosis. Therefore, this study provides a valuable therapeutic agent (CoQ10NPs) for preventing and treating several HgCl₂-induced hepatorenal disorders.

Keywords: apoptosis; coenzyme Q10; hepatorenal toxicity; inflammation; mercuric chloride; nanoparticles; oxidative stress.

Figure 1

Characterization of coenzyme Q10 coupled to albumin nanoparticles. ((A) Upper panel on left): Hydrodynamic diameter of CoQ10NPs measured with Zetasizer. ((B) Bottom panel on left): Surface charge of CoQ10NPs expressed as zeta potential. ((C) Upper panel on right): FT-IR spectra of CoQ10. ((D) Bottom panel on right): FT-IR spectra of coenzyme Q10 coupled to albumin nanoparticles.

Figure 2

Palliative effects of coenzyme Q10-loaded albumin nanoparticles (CoQ10NPs, 10 mg/kg, orally, for 14 days) on serum hepatic and renal function biomarkers upon exposure to mercuric chloride (HgCl₂, 5 mg/kg, i.p., three times a week). Data are expressed as mean ± SD (n = 8/group). The symbol ^# means a significant difference from the control group, while ^$ means a significant difference from the HgCl₂ group at p-value < 0.05.

Figure 3

Palliative effects of coenzyme Q10-loaded albumin nanoparticles (CoQ10NPs, 10 mg/kg, orally, for 14 days) on the hepatorenal oxidative stress markers malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) upon exposure to mercuric chloride (HgCl₂, 5 mg/kg, i.p., three times a week). Data are expressed as mean ± SD (n = 8/group). The symbol ^# means a significant difference from the control group, while ^$ means a significant difference from the HgCl₂ group at p-value < 0.05.

Figure 4

Palliative effects of coenzyme Q10-loaded albumin nanoparticles (CoQ10NPs, 10 mg/kg, orally, for 14 days) on hepatorenal antioxidant molecules (reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT)) upon exposure to mercuric chloride (HgCl₂, 5 mg/kg, i.p., three times a week). Data are expressed as mean ± SD (n = 8/group). The symbol ^# means a significant difference from the control group, while ^$ means a significant difference from the HgCl₂ group at p-value < 0.05.

Figure 5

Palliative effects of coenzyme Q10-loaded albumin nanoparticles (CoQ10NPs, 10 mg/kg, orally, for 14 days) on hepatorenal inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), nuclear factor Kappa (NF-ĸβ), and transforming growth factor β (TGF-β)) upon exposure to mercuric chloride (HgCl₂, 5 mg/kg, i.p., three times a week). Data are expressed as mean ± SD (n = 8/group). The symbol ^# means a significant difference from the control group, while ^$ means a significant difference from the HgCl₂ group at p-value < 0.05.

Figure 6

Palliative effects of coenzyme Q10-loaded albumin nanoparticles (CoQ10NPs, 10 mg/kg, orally, for 14 days) on the hepatic level of alpha-smooth muscle actin (α-SMA) upon exposure to mercuric chloride (HgCl₂, 5 mg/kg, i.p., three times a week). Data are expressed as mean ± SD (n = 8/group). The symbol ^# means a significant difference from the control group, while ^$ means a significant difference from the HgCl₂ group at p-value < 0.05.

Figure 7

Palliative effects of coenzyme Q10-loaded albumin nanoparticles (CoQ10NPs, 10 mg/kg, orally, for 14 days) on hepatorenal apoptotic markers (Bcl-2-associated X protein (Bax), caspase-3, and B-cell lymphoma 2 (Bcl2)) upon exposure to mercuric chloride (HgCl₂, 5 mg/kg, i.p., three times a week). Data are expressed as mean ± SD (n = 8/group). The symbol ^# means a significant difference from the control group, while ^$ means a significant difference from the HgCl₂ group at p-value < 0.05.

Figure 8

Palliative effects of coenzyme Q10-loaded albumin nanoparticles (CoQ10NPs, 10 mg/kg, orally, for 14 days) on histological changes in the liver upon exposure to mercuric chloride (HgCl₂, 5 mg/kg, i.p., three times a week). Scale bar = 80 µm (400×). (A) Control group, (B) CoQ10 group, (C) HgCl₂ group, (D) CoQ10-HgCl₂ group, (E) CoQ10NPs-HgCl₂ group.

Figure 9

Palliative effects of coenzyme Q10-loaded albumin nanoparticles (CoQ10NPs, 10 mg/kg, orally, for 14 days) on histological changes in the kidney upon exposure to mercuric chloride (HgCl₂, 5 mg/kg, i.p., three times a week). Scale bar = 80 µm (400×). (A) Control group, (B) CoQ10 group, (C) HgCl₂ group, (D) CoQ10-HgCl₂ group, (E) CoQ10NPs-HgCl₂ group.