N-acetylcysteine-amide improves tissue oxidative stress, DNA damage, and proteins disappearance in methamphetamine toxicity more efficiently than N-acetyl-L-cysteine - 07/03/21

Doi : 10.1016/j.toxac.2021.02.002

Khaled M.M. Koriem ^a,⁎ , Adley Y. Selim ^b, Ramzy A. Mazen ^c
^a Department of Medical Physiology, Medical Research Division, National Research Centre, 33 El-Buhouth Street, Dokki, Cairo, Egypt
^b Faculty of Pharmacy, Cairo University, Cairo, Egypt
^c Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt

^⁎Corresponding author.

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Summary

Objective

The aim of the present study is to discover a new protective agent to protect against oxidative stress, DNA damage, and proteins disappearance in brain, liver, and kidney in methamphetamine (METH) abusers.

Methods

Forty male albino rats were divided into 4 equal groups: (1) Control, (2) METH, (3) N-acetyl-L-cysteine (NAC, 500mg/kg body weight (bwt))+METH, (4) N-acetylcysteine-amide (NACA, 250mg/kg (bwt))+METH. Group 1 was injected (i.p) with saline (1ml/kg bwt) while groups 2,3 & 4 were injected (i.p) with 4 injections with METH (10mg/kg bwt) every 2hours over an 8-hour period. NAC and NACA were injected 30minutes before METH injections. Reduced glutathione (GSH), glutathione peroxidase (GPx), lipid peroxidation (MDA), catalase (CAT), and protein carbonyl levels were measured in the brain, liver, and kidney tissues. The DNA and protein contents of brain, liver, and kidney tissues were also detected.

Result

The results indicated that METH induced oxidative cell stress by increasing MDA while decreasing cell GSH and the antioxidant enzymes such as CAT and GPx levels. METH induced DNA damage and proteins disappearance in brain, liver and kidney tissues. NAC or NACA injection before METH injection prevented oxidative stress, DNA damage, and proteins disappearance in brain, liver and kidney of METH-injected rats and NACA was more effective than NAC in treated animals.

Conclusion

NACA was more effective than NAC in treated animals through preventing tissue oxidative stress, DNA damage, and proteins disappearance in METH toxicity than NAC.

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Keywords : N-acetyl-L-cysteine, N-acetyl-cysteine-amide, Methamphetamine, Oxidative stress, DNA, Liver, Kidney