Evaluation of the Efficacy of Glutathione Administration in Acetaminophen-Induced Hepatotoxicity in Experimental Rats

محورهای موضوعی :

Reham Nafad Elbendary ¹ , Ghada Hassabo ² , Abeer Mostafa ³ , Dina Sabry ⁴ , heba Abdelmonaem Ibrahim ⁵ , Amr Mohamed Tawfik Khattab ⁶

1 - Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Cairo University, Cairo, Egypt
2 - Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Cairo University, Cairo, Egypt
3 - Medical Biochemistry and Molecular Biology department, Cairo University, Cairo, Egypt
4 - Medical Biochemistry and Molecular Biology department, Cairo University, Cairo, Egypt
5 - Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
6 - Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Cairo University, Cairo, Egypt

تاریخ دریافت : 1399/07/13 تاریخ پذیرش : 1401/04/11 تاریخ انتشار : 1402/12/26

کلید واژه: DNA damage, Liver function, GSH, Comet assay, APAP hepatotoxicity,

چکیده مقاله :

One of the most common causes of acute liver failure is acetaminophen overdose. The antidote N-acetylcysteine acts by scavenging the reactive metabolite, but its therapeutic limitation necessitates the development of additional therapeutic approaches that can benefit late-presenting patients. Glutathione (GSH) is the most abundant intracellular nonprotein thiol that has an important role in the regulation of many cellular physiologic functions such as redox-homeostatic buffering. This study aims to evaluate the efficacy of GSH supplementation in the recovery of deteriorated liver functions in induced acute acetaminophen toxicity rats; in addition to determining its value in the preservation of DNA integrity in such toxicity. This experimental study was done on 36 albino rats which were divided into three groups (n=12 rats / group) as follows, group1: Control group, group 2: Acetaminophen (APAP) treated group, group 3: APAP and glutathione treated group. Each group was subdivided into 2 subgroups (n=6) and they were sacrificed at 12 hours and 24 hours sequentially. The extent of hepatic inflammation, oxidative stress, and DNA damage was evaluated using histopathological study, and comet analysis, and biochemical markers (ALT, GSH, and MDA). GSH supplementation (APAP and glutathione treated group) significantly improved liver functions resulting in; a statistically significant decrease in ALT levels, reducing Malondialdehyde (MDA) levels, and preserving DNA integrity. GSH is a highly effective alternative in the treatment of APAP hepatotoxicity.

چکیده انگلیسی:

One of the most common causes of acute liver failure is acetaminophen overdose. The antidote N-acetylcysteine acts by scavenging the reactive metabolite, but its therapeutic limitation necessitates the development of additional therapeutic approaches that can benefit late-presenting patients. Glutathione (GSH) is the most abundant intracellular nonprotein thiol that has an important role in the regulation of many cellular physiologic functions such as redox-homeostatic buffering. This study aims to evaluate the efficacy of GSH supplementation in the recovery of deteriorated liver functions in induced acute acetaminophen toxicity rats; in addition to determining its value in the preservation of DNA integrity in such toxicity. This experimental study was done on 36 albino rats which were divided into three groups (n=12 rats / group) as follows, group1: Control group, group 2: Acetaminophen (APAP) treated group, group 3: APAP and glutathione treated group. Each group was subdivided into 2 subgroups (n=6) and they were sacrificed at 12 hours and 24 hours sequentially. The extent of hepatic inflammation, oxidative stress, and DNA damage was evaluated using histopathological study, and comet analysis, and biochemical markers (ALT, GSH, and MDA). GSH supplementation (APAP and glutathione treated group) significantly improved liver functions resulting in; a statistically significant decrease in ALT levels, reducing Malondialdehyde (MDA) levels, and preserving DNA integrity. GSH is a highly effective alternative in the treatment of APAP hepatotoxicity.

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