Liposomal coenzyme Q10 abates inflammation, apoptosis and DNA damage induced by an overdose of paracetamol in rat's liver

Abstract

Objectives: Paracetamol (PCM) is widely used for its pain-relieving and antipyretic properties. However, acute intoxication of PCM remains one of the most common causes of drug-induced hepatic failure. A comparative study is conducted to evaluate the effectiveness of coenzyme Q10 (CoQ10) with that of liposomal CoQ10 (L-CoQ10) against PCM-induced liver injury. Method: Acute liver injury was induced by a single oral dose of PCM (1000 mg/kg). CoQ10 and L-CoQ10 treatments were given orally (10 mg/kg), 1 and 12 h following PCM intoxication. Specific oxidative stress, inflammatory and apoptotic biomarkers were measured, and then proved by histopathological examination. Results: PCM administered rats exhibited a remarkable increase in the levels of serum aminotransferase enzymes, as well as hepatic interleukin-6, C-reactive protein, malondialdehyde (MDA) and nitric oxide (NO); whereas reduced glutathione (GSH) level and superoxide dismutase (SOD) activity were decreased. BAX, Nuclear factor-kappa B (NF-κB) and cytochrome C were overexpressed, while BCL-2 was downregulated. The results of the previous parameters were supported by histopathological study of liver tissue. Using either CoQ10 or L-CoQ10 caused a significant reduction of oxidative stress by enhancing GSH and SOD activity levels and diminishing MDA and NO levels. Moreover, both CoQ10 and CoQ10 caused downregulation of pro-inflammatory cytokines and BAX, and upregulation BCL-2, and these effects mostly noticed in L-CoQ10 treated rats. Likewise, rats receiving L-CoQ10 exhibited restoration of normal hepatic architecture. Conclusion: L-CoQ10 supplement is useful for counteracting the hepatotoxicity induced by PCM overdose, via reducing the oxidative stress, inflammation and apoptosis.

Keywords

• Paracetamol
• L-CoQ10
• Cytochrome C
• BAX
• BCL-2