The Potential Protective Effect of Curcumin and α-Lipoic Acid on N-(4-Hydroxyphenyl) Acetamide-induced Hepatotoxicity Through Downregulation of α-SMA and Collagen III Expression

Abstract

Background and objectives N-(4-hydroxyphenyl) acetamide (NHPA) is the most commonly used analgesic and antipyretic agent worldwide; however, it remains the leading cause of drug-induced acute liver failure. This study explored the potential impact of curcumin (Curc) and/or α-lipoic acid (Lip acid) on liver damage induced by NHPA overdose. Materials and Methods Male Wistar rats were intoxicated with a single oral dose of NHPA (1000 mg/kg) and treated with Curc (200 mg/kg p. o.) and/or Lip acid (100 mg/kg i. p.). These treatments were given in 2 doses at 2 hours and 10 hours post-NHPA-administration. Animals were sacrificed 24 hours post-NHPA-administration. Results Treatment with Curc and/or Lip acid showed effective reduction of NHPA-induced liver injury, demonstrated by reducing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, as well as hepatic nitric oxide and malondialdehyde. Curc and/or Lip acid treatments counteracted these changes. They also ameliorated NHPA-induced centrilobular hepatocellular necrosis, evidenced by histopathological examination. Moreover, Curc and Lip acid reduced the expression of alpha-smooth muscle actin and collagen III, upregulated by NHPA intoxication in response to oxidative stress and inflammation. Discussion and Conclusion Curc and Lip acid can be considered as promising natural therapies against liver injury, induced by NHPA, through their antioxidant and antifibrotic actions.

The Potential of Alpha Lipoic Acid to Maintain Liver Function Tests in XenobioticInduced Liver Toxicity: A Narrative Review

“…30 Curcumin and ALA can be considered as promising natural therapies against liver injury, induced By N-(4hydroxyphenyl) acetamide, NHPA, through their antioxidant and antifibrotic actions. 31 ALA and spirulina ameliorate aspartameinduced hepatic injury. 32 Biomarkers of cardiac,renal and hepatic damage are reduced by alpha lipoic acid and/or sesame oil (SO).They also restore antioxidant enzymes and reduce lipid peroxidation.…”

Modulation of Autophagy and Mitochondrial Dynamics Gene Expression by Turmeric and Mangosteen Peel Extract

“…Therefore, alternative herbal ingredients which have the same properties and protective to the liver are needed to be explored. Turmeric and mangosteen peel extract are known for their antioxidant, antihyperlipidemic, and anti-inflammatory properties (Alhusain et al, 2022;Feng et al, 2019;John et al, 2021;Suttirak & Manurakchinakorn, 2014). Curcumin in turmeric and α-mangostin in mangosteen pericarp also have roles in regulating mitochondrial function and reducing mitochondrial dysfunction (Sathyabhama et al, 2022;Tsai et al, 2016).…”